COVID-19

This article describes an infectious disease, the pathogen of which has only been intensively researched since 2020. The information can therefore change quickly.

Classification according to ICD-10
U07.1	COVID-19, virus detected
U07.2	COVID-19, virus not detected
ICD-10 online (WHO version 2019)

COVID-19 (Abbreviation for English co rona vi rus d isease 20 19 , German  Coronavirus- Kranken -2019 , in German-speaking countries also known colloquially as Corona or Covid ) is a reportable infectious disease . It is caused by the coronavirus ( German  'Kranzvirus' or 'Kronenvirus' ) SARS-CoV-2 (including its variants ) and has a broad, unspecific spectrum of symptoms. The virus was first discovered in Wuhan in December 2019 (People's Republic of China ). It spread worldwide very quickly and is the cause of the COVID-19 pandemic . By December 29, 2021, more than 280 million people infected with COVID were registered worldwide; the number of unreported cases in many countries is estimated to be significantly higher. Over 5.4 million people have been registered as fatalities related to COVID illness; Here too, the number of unreported cases is high.

The infection with SARS-CoV-2 is effected by droplet infection (inhaling virus-prone aerosols ) - especially staying in closed and insufficiently ventilated rooms. The Robert Koch Institute (RKI) has not ruled out the possibility of smear infection from contaminated surfaces. To avoid infection, spatial distancing ("social distancing"), contact restrictions, the wearing of a medical protective mask and hygiene measures are recommended.

There are many indications that the spread of COVID-19 into a global pandemic was facilitated in particular by " superspreading ".

The incubation period of COVID-19 averages five to six days; However, up to two weeks can pass between infection and the appearance of the first symptoms . Occasionally, the first symptoms appear within 24 hours of being infected. It is particularly treacherous that an infected person can be infectious (contagious) days before the first symptoms appear and even after they have subsided .

The course of the disease is unspecific and can vary widely. According to an estimate by the RKI, 55 to 85% of those infected have noticeable symptoms and / or show recognizable signs of an illness ( symptoms ) or typical symptom combinations ( syndrome ) of a COVID-19 disease ( manifestation index ). The other infected people are symptom-free and show no symptoms; they are asymptomatic illness, but can the virus still spread . In around 81% of the registered diseases, a mild course with fever or mild pneumonia , dry cough and fatigue can be observed. Less common are nasal congestion , headache , sore throat , body aches , conjunctivitis , diarrhea , vomiting , loss of taste and smell , rash, or discoloration of fingers or toes. In around 14% of cases, the course is more severe, and in around 5% so severe that the patient has to be ventilated in an intensive care unit . If COVID-19 is severe, bilateral pneumonia and acute lung failure occur; those affected can die. Pathological processes of the liver, the central nervous system , the kidneys, the blood vessels and the heart were also observed .

Persistent complaints after the illness, also known as " Long COVID ", occur relatively frequently - both in people who are initially seriously ill and in young, healthy people who are initially only slightly ill. They can lead to long-lasting, chronic complaints in many organ systems. With over 100,000 participants in COVID vaccination studies, however, no evidence of long covid was observed (as of December 2020) . Long Covid is the subject of ongoing research.

COVID-19 has been researched intensively since the beginning of the pandemic and the results are shared internationally. In order to inform other specialists about the latest research results in a timely manner, it is customary to publish current studies as preprints on special servers on the Internet. Publications in social media, but also in the press, radio and television, should not only be based on these unaudited studies, but also on publications by reputable and professionally competent institutions - such as B. of the RKI , WHO , NHS or CDC . Some of these are based on peer reviews of the studies in question, to which reference is also made there.

As early as the end of 2020, COVID vaccines were approved and vaccination campaigns started in the European Union and in some non-EU countries . The Science Magazine Science explained the development of vaccines against SARS-CoV 2 unprecedented speed to the scientific breakthrough of the year ( Breakthrough of the Year ).

designation

On February 11, 2020, the WHO established the acronym "COVID-19" as the official name. It comes from the English: CO for Corona , VI for Virus , D for Disease and 19 for the year of the first description 2019.

Transmission path

Transmission and life cycle of the pathogen SARS-CoV-2 causing COVID-19

The cause of the disease is the beta coronavirus SARS-CoV-2 , which was first identified in January 2020 on the basis of isolates from pneumonia patients. The virus has so far been detected in the secretion of the nose and throat , in sputum , in stool, tear fluid, in blood, in aerosols and on surfaces. The main transmission route for SARS-CoV-2 is the respiratory uptake of virus-containing liquid particles (breathing, coughing, speaking, sneezing). Other ways of infection (stool, tear fluid, blood) have not been conclusively clarified.

On January 20, 2020, the Chinese Health Commission announced that human-to-human transmission was possible, especially when two people are in close contact (less than 1.8 m away or less than 1.5 m away).

Aerosol and droplet infection

A man sneezes - extensive swaths of droplets of saliva are ejected in a cone shape

It is believed that the virus, like other respiratory pathogens, mainly spreads through particles containing the virus. These are released by infected people while breathing, coughing, sneezing, speaking and singing and then ingested by healthy people. The transition between aerosol and droplet infection is fluid. The World Health Organization (WHO) defines droplets as particles with a diameter of 5 to 10 micrometers (μm). Due to their size, unlike the much smaller aerosol particles , droplets sink relatively quickly to the ground. These are only approx. 0.001 to 5 μm in size and are distributed over greater distances with the air currents in rooms and buildings; depending on their size and density, they can stay in the air for a very long time. The risk of transmission through aerosols is much higher in activities with high particle emissions such as speaking loudly or singing in small, poorly ventilated rooms than outdoors. Therefore, effective measures to prevent infection must be defined and implemented, especially for apartments, offices, classrooms, residential complexes and care facilities .

In air-conditioned interiors, e.g. B. in hospitals, droplets in the size range from 5 to 40 μm - due to their aerodynamic behavior as "jet riders" (transport with air jet and air conditioning-induced air movement, falling out at a greater distance, poor elimination with ventilation) - quite transmit pathogens particularly well .

In the open air there are almost no infections caused by aerosol particles. However, droplet infections can occur, especially in crowds, if minimum distances are not observed and / or masks are not worn.

A biophysical study by MIT experimentally found in early 2020 that fluid particles can be spread widely up to eight meters without a mechanical barrier when coughing or sneezing. This calls into question the droplet infection paradigm that dates back to the early twentieth century. Based on an evaluation of virus genomes at superspreading events, researchers estimate that most infections occur when around 1,000 virus particles are transmitted. However, infections from lower doses of the virus are also possible.

Based on quantitative analyzes of RT-PCR examinations of the nasopharynx , Chinese researchers wrote in February 2020 that the virus, like influenza, can also be transmitted by aerosols . A study by the US American NIAID supports this view on the basis of quantitative viral load determination in aerosols. The investigation has shown that the viruses in aerosols, which were generated by a mechanical nebulizer, remained viable and thus infectious for at least three hours. It took about 66 minutes for half of the viruses to lose their infectivity in aerosols. A meta study of 24 studies showed that of 473 examined air samples from hospitals with COVID patients contained 17% genetic material of the virus and in 9% of the examined samples the virus could be grown in culture. Air samples taken close to the patient as well as air samples taken away from the patient showed virus-containing aerosols.

In 3 of 63 patients with pneumonia COVID-19 were swabs from the eye conjunctiva PCR -positive. The study authors noted, however, that no clinical data would indicate the route of spread. The Robert Koch Institute writes (as of August 17, 2021): In three (of 63 examined) patients with COVID-19 pneumonia conjunctival samples were PCR-positive [... ]. However, this is not evidence that conjunctives can act as a gateway. In an animal study (March 2020), a rhesus monkey was infected with SARS-CoV-2 via the conjunctiva and showed mild symptoms

In some patients examined with symptoms of the disease, the amount of virus in the nose was higher than in the throat; the occurrence in the upper respiratory tract distinguishes SARS-CoV-2 from the SARS- causing SARS-CoV- 1. Sample examinations of the patients belonging to the Munich cluster show that the existing viral load in the nasopharynx was higher by a factor of 1000 than with previously known coronavirus diseases such as SARS and MERS . A study could not find any difference in viral load among the different age groups.

Contact transfer

In a very small study it was shown that the polymerase chain reaction (PCR) in the sleeping and washing rooms of corona patients can detect high viral loads on textiles and the surfaces themselves. Since no virus culture was carried out in the study, the infectivity has not been conclusively proven. The Federal Institute for Risk Assessment (BfR) wrote in May 2020 that no cases had been proven in which people had been infected with SARS-CoV-2 through consumption of contaminated food or through contact with contaminated objects. Since the stability of coronaviruses in the environment is relatively low, such an infection would only be conceivable within a short period of time after the contamination.

An evaluation of 22 studies that examined the persistence of medically relevant coronaviruses (such as SARS-CoV and MERS-CoV ) on surfaces shows that these viruses can persist for up to nine days on surfaces made of metal, glass or plastic at room temperature. On average, they remain infectious for four to five days. They can be inactivated with suitable disinfectants . According to the scientists involved, these findings can probably be transferred to SARS-CoV-2. Preliminary laboratory tests on SARS-CoV-2 show that the virus can remain infectious on plastic and stainless steel for up to three days, but not longer than a day on cardboard or longer than four hours on copper. UV light kills the viruses in a short time. According to the Robert Koch Institute, infection through contaminated surfaces “cannot be ruled out, especially in the immediate vicinity of the infected person”. The ECDC wrote in March 2020 that the virus could be transmitted through droplet-covered surfaces. The US National Institutes of Health wrote in March 2020, after quantitative studies of the viral load in various scenarios, that transmission through contaminated objects and surfaces can take place because the virus can occur several hours (in special cases even up to three days) after Contamination outside the human body is detectable.

On the basis of investigations using virus culture, it could be shown that, depending on the environmental conditions, there is an infectiousness even after the virus has been on objects.

Overall, the importance of contact transmission for the COVID-19 pandemic is low to very low.

Breastfeeding and breast milk

The SARS-CoV-2 is not in infected mothers in the breast milk proved. On the other hand, specific antibodies against SARS-CoV-2 are found in the breast milk of the infected women, which can protect the baby or toddler in the event of an infection. The WHO's recommendation since the beginning of the pandemic has been: Even with SARS-CoV-2 infection, breastfeeding should continue to be promoted and supported. Although the virus is not transmitted through breast milk, the risk of infection through aerosols must be minimized, which is why we recommend wearing a mask, frequent hand washing and frequent disinfection of surfaces even when breastfeeding if the mother is infected with COVID-19.

The WHO stressed that it is particularly important that newborns are not systematically separated from their mothers when there is a suspicion of COVID-19.

Other means of transmission

Researchers from Singapore recommend treating the patient's stool as infectious due to the virus detection in the stool and the detection of infectious coronaviruses in the wastewater of two Chinese hospitals during the SARS pandemic of 2002/2003 . In order to rule out the possibility of a fecal-oral route of infection in addition to droplet and aerosol infections, further studies of both the virus excretion of the patients and the potentially contaminated environment are necessary. Sample examinations using virus culture of the 16 patients belonging to the Munich cluster, however, show that their stool was not virulent , although virus RNA could be detected. In contrast, Chinese researchers report two cases without diarrhea symptoms, in which virus culture and electron microscopy were able to detect a virus capable of replication in the stool. This could be confirmed by another research group. A cell culture model with wastewater samples containing virus RNA could not detect any virus capable of replication.

Transmission in the womb has been proven in several individual cases.

Base reproduction number

The evaluation of the data from the first 425 cases in Wuhan resulted in a base reproduction number of 2.2 - which means that each infected person infected an average of 2.2 other people. A model calculation with Chinese and foreign patient data from December 31, 2019 to January 28, 2020 resulted in a value of 2.68. An evaluation of the early stage of the outbreak on the cruise ship Diamond Princess came to a value of 2.28. In comparison, a base reproduction number of 2.3 to 2.6 was calculated for SARS. A comparative evaluation of 12 studies published by February 7, 2020 comes to the conclusion that the base reproduction number is higher than previously assumed by the WHO, whose estimate is 1.4 to 2.5. The scientists from Sweden, China and Germany estimated that the base reproduction number is on average 3.28, the median 2.79 (with an interquartile range of 1.16) - and thus above the value for SARS, which they have with 2 to 5 specify. The current estimates of the mean base reproduction number may be biased due to the inadequate data situation. In an article published on April 7, 2020, the Centers for Disease Control and Prevention estimated the base reproduction number without containment measures to be 5.7 with a 95% confidence interval of 3.8 to 8.9. ${\displaystyle R_{0}}$

An international study that examined 539 social contacts of a patient found that this patient had infected 2 out of 7 close social contacts and 3 out of 473 casual social contacts.

In a mathematical infection model developed by Christophe Fraser, Luca Ferretti and colleagues, the base reproduction number (according to the authors, the value 2.0) can be divided according to the type of transmission: presymptomatic, asymptomatic, symptomatic and via environmental contact (e.g. smear infection). According to this, the value from presymptomatic transmission alone is 0.9 (corresponding to 46 percent of the total value of ), i.e. almost sufficient to keep an epidemic going. According to the authors, the contribution of the symptomatic carriers is 0.8, the asymptomatic 0.1 and the environmental 0.2. According to the study, the generation time averages 5.0 days. The study also examined the chances of success of isolating symptomatic individuals and manual contact tracing using its mathematical simulation, and concluded that they are not fast enough to stop the epidemic. (They recommend using apps on cell phones.) ${\displaystyle R_{0}}$ ${\displaystyle R_{0}}$

Super spreading

COVID-19's propensity for superspreading is indicated by over- dispersion . Overdispersion describes the phenomenon of a high individual-specific variation in the distribution of the number of secondary transmissions that can lead to "super- proliferation events ". The degree of over-dispersion can be estimated using a statistical model in which the distribution of secondary transmissions is characterized by the over- dispersion parameter and the base reproduction number . The over-dispersion parameter quantifies the variability in the number of secondary cases and can be interpreted as a measure of the effect of superspreading. The smaller the estimated over-dispersion parameter, the stronger the effect of superspreading. The interpretation of the estimated over-dispersion parameter is simplified by focusing on the proportion of individuals responsible for 80% of secondary transmissions (an empirical pattern known as the 80/20 rule ). If the over-dispersion parameter is small ( ), it approximates the proportion of infected people who cause 80% of infections. For example, an estimated over-dispersion parameter of 0.1 would mean that the most infectious 10% of people cause about 80% of infections. ${\displaystyle \kappa }$ ${\displaystyle R_{0}}$ ${\displaystyle \kappa \ll 1}$

Julien Riou and Christian Althaus came to the conclusion through simulations that the estimated over-dispersion parameter for COVID-19 is slightly higher than that for SARS-CoV and MERS-CoV . In a preprint of Gabriel Leung and colleagues in the Kontaktpersonennachverfolgung were used -sdaten to SARS-CoV-2 cluster to identify in Hong Kong and characterize the over dispersion parameters were estimated 0.45 (95% CI: [0.31 -0.76]). This represents a considerable individual heterogeneity in the transferability of SARS-CoV-2 and is thus associated with a high potential for future superspreading, but according to their results less strong than with SARS-CoV and MERS-CoV. Later studies assume an estimated over-dispersion parameter of around 0.1. There is empirical evidence that the distribution of the number of secondary transmissions has “ bold distribution ends ”. Extraordinary transmission events are therefore extreme, but nevertheless probable events that make a considerable contribution to the overall transmission (see in detail in overdispersion # application in epidemiology ).

Incubation time, serial interval and period of infectivity

Course of disease

incubation period

The incubation period (ie the time between infection and onset of the disease) can be noisy information from the Robert Koch Institute, up to 14 days (RKI). The RKI and a statistical analysis of several reports of infections in a household or in other narrow spatial limits (so-called clusters ) put the median incubation time at 5–6 days . In Korea, using data from 303 patients with an average age of 25 years, the period between the first positive test and symptoms of the disease was determined to be 15 days (Ø). The decay time to negative test was 19.5 days in symptomatic and 17 days in asymptomatic patients. An analysis of the first 425 cases reported in Wuhan showed an incubation period of 5.2 days on average and an average age of 59 years. The authors assumed that human-to-human transmissions had already taken place in the vicinity of the fish market in mid-December 2019.

Infectivity during the incubation period and during the course with or without symptoms

Infection to other people during the incubation period is possible despite the symptom-free state of health. Tests of the viral load in the sputum of patients also suggest that some patients may continue to be temporarily infectious as they heal and with clinical improvement. In a group of 126 people evacuated from Wuhan to Germany, two patients showed positive RT-PCR of the throat swab who showed no or only very unspecific symptoms. A case of a subjectively asymptomatic ten-year-old boy in Shenzhen is also described, whose blood count and signs of inflammation in the laboratory were normal. Further examination, however, showed radiological findings compatible with pneumonia, and viral RNA could be detected in the throat swab.

In a February 2020 study of a family of three from Guangzhou , all family members were PCR positive, but only the father showed symptoms. The authors hypothetically considered it possible that the father could not have been patient 1, but that the other two asymptomatic persons could also have been considered, and therefore warned of the risk of the virus spreading by symptom-free patients in the early stages of the infection. Measurements of the viral load in the secretion of the nasopharynx of 14 patients diagnosed with COVID-19 showed a similarly high viral load in symptom-free patients (one of 14 examined) and those with symptoms (13 of 14 examined, of which ten were mildly to moderately ill and three were seriously ill that they needed intensive medical treatment). On the basis of quantitative virus examinations in the secretion of the nasopharynx in patients with very mild symptoms , the researchers at the Charité Virology Department and the Bundeswehr Institute for Microbiology concluded that even very mild symptoms of the disease are highly infectious. The Robert Koch Institute has also reported on individual cases in which those affected may have contracted infected people who had no or no specific symptoms. Chinese case observations in which asymptomatic patients infected other people at home came to the same conclusion.

Another study from China, based on contact person tracking and virus genome analysis, suggested that the formation of an infection cluster was due to an asymptomatic person. Suspected asymptomatic patient 1 returned from the United States on March 19, 2020 and was asked to quarantine at home. She lived in the same house, but was never in physical contact with those who were later infected and was never tested positive for PCR herself. About 20 days after the cluster was suspected to be infected, her IgG value was positive, indicating to the authors that she had previously been infected with SARS-CoV-2. The authors therefore believed (“we believe”) that she was the asymptomatically infected and that patient 2 was infected through contact with surfaces in the elevator of the building in which they both lived. In addition, an analysis of the virus genome showed that it differed from the genome previously circulating in China - an indication ("indicating") for the authors that it came from abroad and that patient 1 was probably ("suggesting") the origin of the infection tree.

In a study on 191 hospital patients, Chinese researchers showed a positive RT-PCR test result for the 137 survivors for an average of twenty days with a variance between eight and 37 days. An analysis of infections in Singapore and Tianjin found that 48% to 62% of infections were transmitted from people who were COVID-19 infected but did not yet show symptoms.

A major difference to the SARS coronavirus is that patients can be infectious a few days before the onset of the symptoms of the disease (with the SARS coronavirus, on the other hand, the patients were only infectious after the symptoms appeared). The infection is therefore more difficult to detect and more difficult to contain. In the case of quarantine measures, it is therefore not sufficient to just isolate the clinically suspicious people. A Chinese research published in April 2020 confirmed the major role of presymptomatic transmission in COVID-19. From the data they calculated (as later showed, with a calculation error, see below) that the infectiousness began 2 to 3 days before the onset of symptoms in the cases examined. 94 cases from a hospital in Guangzhou were examined, in which the temporal course of the viral load in the throat was determined. It was already pronounced at the onset of the symptoms and then showed a drop. In addition, 77 cases of couples from a chain of infection inside and outside of China were investigated. This showed that in 44 percent the infection took place before symptoms developed in the infected person. The infection period began on average 2.3 days before the onset of symptoms and had a peak 0.7 days before the onset of symptoms. The infectivity decreased rapidly within a week. The serial interval averaged 5.8 days. During a follow-up examination of the data from Leung and colleagues, a team led by Sebastian Bonhoeffer from ETH Zurich found an error in the computer program that accidentally left out two data points. In fact, the infectious period started about 5 days before symptoms began. The proportion of presymptomatic cases of infection of around 45 percent remains the same. Leung and colleagues have admitted the mistake. The correction also affects the contact tracing, which would have to be extended to 5 to 6 days before the onset of symptoms (instead of the previous 2 to 3 days).

Infectiousness of those who have recovered

Doctors from Sun Yat-sen University in Guangzhou report a case that, after a mild course and two negative RT-PCR results from smear material, again showed positive virus detection without any symptoms. The study authors recommend routine tests and a two-week quarantine even for symptom-free people who have healed to prevent potential new infections. In March 2020, a study from Beijing found that 22 of 133 discharged patients with a negative throat swab still had detectable viral RNA in the stool or sputum. The authors recommended RT-PCR testing that goes beyond the throat swab to exclude the risk of infection by discharged patients.

The World Health Organization reported in its weekly "Epidemiological Update" in August 2021 to the risk of re-infection, in the conditions prevailing in Germany Delta variant a reduction of immunity would be reported.

Serial interval

The serial interval , ie the time interval from the onset of the disease a person at the beginning of the disease one of her infected person in a chain of infection, amounted to a study published in January 2020 Chinese study with 425 patients on average 7.5 days ( standard deviation 3, 4 days), according to another study with 28 cases 4 days. A study with 468 confirmed pairs of infections from all over China in January / February 2020 also came to a serial interval of on average 3.96 days (95% - confidence interval 3.53 to 4.39 days, standard deviation 4.75 days). This included 59 cases (12.6 percent of the cases) in which the infected person had symptoms earlier than the person who was infected.

In a study of 312 transmissions, the mean value of the serial interval was given as 4.46 days. In it, transmissions were found on the first day after the infection. The risk of transmission was highest on the third day. After 10 days the risk of transmission decreased significantly, but was still present.

Disease development with COVID-19

Like SARS-CoV- 1 in SARS , the virus SARS-CoV-2, which triggers COVID-19, penetrates human cells via a bond to the enzyme ACE2 anchored in the cell membrane . The viral spike protein interacts with ACE2. The involvement of the serine protease TMPRSS2 is necessary for this process . In the experiment with HeLa cells , the ACE2 of man, Chinese horseshoe bat ( Rhinolophus sinicus ), a Schleichkatzenart , the domestic pig and mouse expressing , was able to use the respective ACE2 protein as a receptor SARS-CoV-2 in order to penetrate into the cell , only with the mouse ACE2 this did not work, nor with HeLa cells that did not produce ACE2. SARS-CoV-2 does not bind to receptors that are used by other coronaviruses.

A reverse search in a human cell type and gene expression database ( Human Cell Atlas , HCA for short ) for cell types and tissues in which, in addition to ACE2, TMPRSS2 is also present on membrane surfaces, showed that in the nasal mucosa it was mainly the goblet cells , but also the ciliated epithelium has the highest concentrations of these two proteins. Therefore, these cells are viewed as the entry portal for SARS-CoV-2 and also assumed to be a reservoir. The proteins are also formed in the corneal cells of the eye, in the intestinal mucosa and in the heart in pericytes of the blood capillaries, heart muscle cells and fibroblasts. The first phase of the infection in the nasopharynx remains almost symptom-free, while the transition to a severe form predominantly affects the lungs, since a large part of the ACE-2-expressing cells in humans occurs in the type II pneumocytes of the lungs. Another reason given for the lung's particular susceptibility is its large surface area, and pneumocyte type II cells also express various genes that promote the replication and transmission of SARS-CoV-2. Investigations on cryopreserved lung tissue samples from non-infected people also showed that lung tissue hardly develops ACE2 or the transmembrane protease TMPRSS2, whereas type II pneumocytes in the lungs increase. These progenitor cells tended to be found more frequently in men and at an advanced age. In addition to different ACE2 values ​​in men and women, a cause for the different severity of the disease in the gender-specific hormone balance is suspected: "Estrogen promotes an immune response, whereas testosterone suppresses it". A role of the proprotease furin , which is formed in the lung epithelium and neighboring tissue cells , which is discussed to simplify cell access for the virus in other coronaviruses, since there is a furin-specific separation point on the spike protein of SARS-CoV-2. In addition to the lungs, ACE-2 has also been found in the small and large intestines, in the airways and in the kidneys. The virus was found to multiply in intestinal cells and islet cells of the pancreas .

By examining lung tissue using biopsies or autopsies, diffuse damage to the alveoli could be demonstrated. This was evident in the formation of hyaline membranes, the thickening of the alveolar walls and the immigration of mononuclear immune cells and macrophages . Virus particles could be detected in type 2 pneumocytes and the cells of the bronchi using an electron microscope. In addition to the changes in the lungs, necrosis of the lymph nodes on the lung hilus, enlargement of the liver with inflammatory cell infiltration, atrophy of the spleen and, in individual patients, isolated degenerate neurons of the brain were observed. It remains unclear whether the damage outside the lungs is directly attributable to the virus or to the general burden on the organism caused by the disease. In another autopsy series, focal-shaped smallest thrombi were found in the pulmonary capillaries even in the absence of larger thromboses in the organism. In addition, a fibrotic remodeling of the lung areas was found in advanced disease. Diffuse alveolar damage, as in classic ARDS, was only seen in patients who had also received invasive ventilation. The authors concluded that the formation of blood clots in the smallest blood vessels was the leading mechanism of COVID-associated lung damage.

The penetration of the virus into the olfactory cells via the nasal mucosa has been proven. It is suspected that the virus has spread to the central nervous system via these nerve cells. A few cases have been diagnosed with Guillain-Barré syndrome , which is often associated with viral infections. The patients were PCR positive - CSF detection was not possible. In the imaging, the cauda equina and the facial nerve were conspicuously visible. Paresthesia and paresis (motor failures) were symptomatic . In another case report, virus-induced encephalitis was also confirmed by positive PCR detection in the cerebrospinal fluid . The German Society for Neurology (DGN) recommends in a guideline issued especially for the COVID disease continuous monitoring, especially of inpatients, but also of outpatients cared for, for early signs of neurological involvement.

X-ray of COVID-19 virus pneumonia

Italian intensive care physicians advocated the presence of two manifestations of COVID-19 viral pneumonia based on their clinical observations in April 2020  . The pneumonia usually start with the L-type , the awarding by a low presence of edema in the tissue. In some of the patients, the transition to an H-type occurs , which is characterized by edema in the tissue. The researchers advocate different approaches to ventilation for these two types. In the presence of extremely low oxygen saturation, which suggests a massive gas exchange disorder and, in conjunction with imaging, clearly indicates acute lung failure (ARDS), German pulmonologists are now deviating from previous guidelines and initially recommend non-invasive ventilation (NIV) with O, which is less invasive for the lungs ₂ enrichment. Other leading pulmonologists also suggested, because of the increased endothelial damage to the affected pulmonary vessels, not the classic ventilation strategy for inflammatory pneumonitis ARDS, but instead, with elasticity still given, with the clinical picture in COVID, which they called CARDS to differentiate, through adapted tidal volumes and expiratory pressures (PEEP ) to adapt.

A histological examination of six deceased patients showed the formation of fibrin balls in the alveoli with an infiltrate of T lymphocytes and plasma cells as well as hyperplasia of type II pneumocytes in advanced lung diseases that are clinically assigned to the H type . In the blood vessels, there were signs of endothelial damage with the formation of vacuoles in the cell plasma and the interruption of the connections between the endothelial cells. The authors hypothesized that the H-type, as a later form of the COVID lung disease, shows the picture of an acute fibrinous organizing pneumonia. An examination of the lungs of seven deceased showed a significantly increased formation of new vessels due to lumen division in the affected pulmonary vessel sections. The authors hypothesized that the pathologically increased formation of new blood vessels contributed to lung damage.

At the transition from mild to severe courses, a virus-induced septic shock is now assumed, which is based on an immunological mechanism. In mild cases, the immune system succeeds in quickly stopping the virus from multiplying in the lungs. In severe cases, however, this is not possible due to the virus-related dysfunction of the directly infected T cells. The virus replication in the lung epithelial cells and also in the inner layer cells of the lung capillaries leads to a capillary leak, which leads to the accumulation of fluid in the alveoli. The uncontrolled virus replication leads to further immigration of monocytes and granulocytes. Inflammatory cytokines and chemokines including TNF-α, interleukin-1β, IL-6, CXCL10 , CCL2 and MIP-1α were significantly increased, which means that immune cells accumulate at the site of inflammation and the immune response is strengthened. The inflammatory reaction in the lungs, together with the spread of the virus to other organs, lead to an excessive immune reaction in the sense of the cytokine storm , which in turn leads to further cell damage locally and subsequently reduces the number of lymphocytes - especially CD4 ⁺ and CD8 ⁺ T cells (Lymphopenia). No significant decrease in effector T cells was observed with mild courses. In severe cases, their increase correlates with the healing of the disease. A small study also found that surviving patients mainly develop IgG antibodies against the spike protein and those who died from the disease mainly develop IgG antibodies against the nucleocapsid.

Another mechanism is the direct release of the specific transcription factor NF-κB , which in turn upregulates IL-6. In addition, an increase in serum AngII can be observed due to the infection -related reduction in ACE2 , which in turn also activates NF-κB, disintegrin and the secretase ADAM17 ( English ADAM metallopeptidase domain 17 ), which activates the mature form of the ligands via the AngII- AT1R axis of the epidermal growth factor receptor ( EGFR ) and TNFα, as well as two NF-κB stimulators. ADAM17 induction also processes the membrane form of IL-6Rα to soluble form (sIL-6Rα), followed by gp130 -mediated activation of STAT3 via the IL-6 / sIL-6Rα complex in IL-6Rα negative cells, such as Fibroblasts, endothelial and epithelial cells . Thus, a SARS-CoV-2 infection in the respiratory tract of both NF-kB and STAT3 activated, which in turn (IL-6 amplifier English IL-6 amplifier , shortly IL-6 Amp) sets in motion a mechanism for further overactivation of NF-κB by STAT3, which leads to various inflammatory and autoimmune diseases . In doing so, the IL-6 enhancer is amplified in a positive feedback loop by inducing various pro-inflammatory cytokines and chemokines, including interleukin-6, and the recruitment of lymphoid and myeloid cells, such as activated T cells and macrophages. This process is known as a cytokine storm and is the cause of acute lung failure in SARS-CoV-2 infection. Since IL-6 is considered to be an important marker for senescence , the IL-6 enhancer could also be considered for the higher mortality among the elderly.

Comparative studies with other forms of acute lung failure and inflammatory syndromes come to the conclusion, however, that the amount of inflammatory mediators released in severe COVID-19 disease is significantly lower than in other diseases associated with a cytokine storm. This is taken as an indication that other mechanisms of disease development such as vascular inflammation, direct viral damage or immunodeficiency induced by the virus also contribute significantly to the severity of the disease.

Interferon-1 is a central regulator of the cellular immune response against viruses. In contrast to other respiratory viruses, COVID is characterized by a decrease in interferon-1 and interferon-3. A reduction in the production of interferon -1 by the virus protein Orf9b was also demonstrated in the cell model. In a study, congenital defects in interferon-1 formation were found in 3.5% percent of the severely examined COVID patients.

Researchers from Wuhan also reported heart muscle damage in a study in March 2020. Around a fifth of the 416 hospitalized patients examined showed damage to the heart muscle as well as damage to the lungs. The cause of the heart damage is not yet clear. They suspected a negative effect of the inflammatory reaction triggered in the context of pneumonia as well as a direct infection and increased stress on the heart due to the lack of oxygen supply and the higher circulatory stress. Autopsies revealed inflammatory infiltrates that correlated with regions of cell death . The picture of myocardial damage in these cases was consistent with myocarditis . Their development without known coronary pre-existing disease was also observed without the involvement of the usual pneumonitis. With age, the expression of ACE2 and TMPRSS2 increases in myocardial cells, through which cell access occurs. The damage to the cardiomyocytes is correlated with the increase in troponin , a typical marker for myocardial infarction. If the pumping weakness of the left ventricle results, this could explain the reduced chances of survival for the elderly. These relationships, as well as a higher expression of an IL-6 receptor on cardiomyocytes in old age, which is responsible for the cytokine storm, was found in postmortem examinations of the heart of patients who did not die from cardiac diseases, but also not from SARS-CoV-2 . In the case of two relatively young and not previously ill patients who had suffered a flu-like infection due to the symptoms described, 4 weeks later there was difficulty in breathing, which suggested a heart muscle dysfunction. PCR tests of the biopsies taken to clarify suspicions were positive, so that the heart disease is suspected to be a result of a SARS-CoV-2 infection. In another case series, the virus genome of SARS-CoV-2 was detected in tissue samples from 104 patients who were examined for suspected myocarditis or other inflammatory heart diseases. In all - between 36 and 62 years old - there was a significant pump weakness and troponin increased in 4 of the 5 patients. The study suggests that heart involvement can be expected after a COVID-19 illness, although direct evidence that the virus attacks the heart muscle has not yet been provided.

Virus replication in the tubule (kidney tubules) with acute damage to the tubule as a result of the subsequent inflammatory reaction could also be demonstrated in individual autopsy cases.

In rare individual cases, the Kawasaki syndrome occurs more frequently in small children . B. Rashes occur. A direct connection with a SARS-CoV-2 infection is suspected. The WHO named this disease multisystem inflammatory syndrome in children (MIS-C). As of July 1st, more than 1000 children worldwide had this rather rare syndrome. One study diagnosed 186 cases with an average age of 8.3 years. The incidence is 2 in 100,000. The first signs about 2 to 4 weeks after infection are high fever, tachycardia , gastrointestinal symptoms, rash, and conjunctival injections. CRP was increased in all, as well as D-dimer levels and troponin in most. About half showed signs of myocarditis, 80% required intensive treatment. Two children died.

Clinical symptoms and laboratory signs

category	Symptoms of COVID-19
Asymptomatic	without symptoms
Common symptoms	Fever cough tiredness
More symptoms	Loss of smell    & taste. Diarrhea. Headache. Sore throat. Body ache. Conjunctivitis. Skin rash
Also reported for the Omikron variant	Runny nose sneeze
Medium gradients	Difficulty breathing slight pneumonia
Heavy gradients	Severe pneumonia, organ failure, death
Source: WHO, autumn 2021

After an incubation period (see above) of an average of 5 to 6 days (in rare cases up to 14 days), the most common symptoms are cough , fever , runny nose and loss of smell and taste . The sick often also suffer from fever, fatigue and neck , muscle , back , head and body aches . In general, the disease often manifests itself in a severe feeling of illness . Other symptoms can include nausea , loss of appetite , vomiting , abdominal pain and diarrhea, as well as conjunctivitis , skin rashes and swelling of the lymph nodes . But there are also cases of asymptomatic courses , especially in those who have been vaccinated. However, their share has not been conclusively clarified.

Heavy gradients

In the further course, usually from the second week of the disease, around 14 percent of patients develop severe shortness of breath due to an infection of the lower respiratory tract and even pneumonia . This can be accompanied by chest pain in the sense of pleurisy and " progress to failure of respiratory and circulatory function " ( ARDS ), which may require intensive medical artificial ventilation and external oxygen saturation of the blood (approx. 5% of all cases). “Some seriously ill people develop a worsening of their condition eight to 15 days after the onset of the disease as a result of severe inflammatory reactions (hyperinflammation syndrome ). As a result, several organs can fail . Many of those affected die. "

The report by the Chinese Center for Disease Control and Prevention ( English Chinese Center for Disease Control and Prevention , in short: CCDC ) over 44,415 cases from Wuhan, the classification is as easier disease when only a slight pneumonia is present or no, are for a severe course Pneumonia (pneumonia), dyspnea (shortness of breath), a respiratory rate of ≥ 30 breaths per minute, blood oxygen saturation ≤ 93% and other clinical signs are typical; if the disease progresses critically, respiratory failure , septic shock and / or multiple organ failure can be expected. The case report found 81% mild disease courses , 14% severe disease courses and 5% a critical disease course. According to the RKI, if the disease progresses slightly, there are often no symptoms or, according to the WHO, they subside within two weeks. People with severe disease take between three and six weeks to recover from the disease.

The majority of hospital admissions of the first patients took place after about a week of symptomatic illness due to deterioration of the condition. In those cases in which intensive medical treatment was necessary, it became necessary about ten days after the onset of symptoms. In an epidemiological study of 99 hospitalized cases in 13 patients found a non-invasive ventilation , in four patients an invasive ventilation , in nine patients a dialysis due to renal failure and in three patients an extracorporeal lung assist (ECLA) application. Clinical observations often describe minor complaints despite respiratory insufficiency that can be measured using an apparatus . Patients who actually required ventilation due to a low oxygen saturation often showed themselves to be relatively symptom-free before their condition rapidly deteriorated due to the oxygen in the organism .

About 85% of seriously ill COVID-19 patients develop lymphopenia , which is a lack of lymphocytes in the blood. Fatal diseases resulted in persistent lymphopenia. The seriously ill patients also often develop hypercytokinemia ( cytokine storm ). A cytokine storm is caused by an overreaction of the immune system. This overreaction is characterized by a significant increase in inflammation-relevant cytokines such as interleukin-6 , interleukin-8 , interleukin-1β and TNF-α . The increased release of these cytokines leads to an overproduction of immune cells, especially in the lung tissue. There further cytokines are released by the immune cells ( coupling ). This uncontrolled immune response leads to serious inflammatory diseases such as pneumonia, shortness of breath and inflammation of the airways. Cytokine storm and lymphopenia are summarized as "lymphopenic community acquired pneumonia " ( L-CAP). L-CAP is associated with severe disease progression, increased mortality, and misdirected immune responses. It is assumed that early detection of this immunological phenotype could be useful in order to be able to identify patients with severe courses in good time. Laboratory tests have shown very high ferritin values ​​as well as greatly increased interleukin-6 or increased values ​​of LDH, D-dimer and a permanent decrease in lymphocytes as factors for an unfavorable prognosis. The majority of patients showed the typical case of severe viral infections combination of a reduction in the number of total white blood cells , a decrease in lymphocytes -Number and an increase in laboratory tests of inflammation (such as CRP and ESR ).

Other manifestations and complications

SARS-CoV-2 also regularly affects the neurological system. In addition to the frequent symptoms of loss of smell and taste, this can also lead to dizziness , confusion , somnolence and other neuropsychiatric symptoms such as SARS-CoV-2 associated ( meningo ) encephalopathies . Also " strokes , cases of Guillain-Barre - and Miller Fisher syndrome are described." At Johns Hopkins University , tissue samples from 23 COVID-19-free patients were found to have the highest expression of the ACE2 enzyme in the area of ​​the nose that is responsible for smelling, which explains the loss of smell in the event of infection.

The cardiovascular system is often affected. Elevated cardiac enzymes and troponin could also be detected in children and “patients with a mild or moderate course” . "Especially with severe respiratory infections suffered by a number of patients of cardiovascular disease , including heart muscle damage, myocarditis , heart attack , heart failure , heart rhythm disorders and venous thromboembolic events . The pathologically increased blood coagulation is associated with severe COVID-19 courses with an increased risk of thromboembolism , including in the lower extremities, as well as pulmonary artery and cerebrovascular embolism and possible consequential damage. "

Cases of liver dysfunction and (especially in patients requiring ventilation) acute kidney failure , some of which require dialysis , are also reported . There are also numerous dermatological manifestations, such as itchy, morbilliform rashes , papules , redness , hives and chilblains- like skin lesions . "In rare cases severe circulatory disorders in the acra up to gangrene have been described."

"Rare cases of Pediatric Inflammatory Multisystemic Syndrome (PIMS) have been observed in children and adolescents ."

See also : Long COVID

Phases and duration of the course of the disease

On the basis of clinical observations and laboratory tests, a three-phase clinical picture is postulated: an early infection phase is followed by a phase in which the lung disease predominates after around five days . In mild courses (approx. 81% of the cases) the symptoms usually subside after around two weeks. If the disease progresses further, however, a phase can occur around the tenth day after the onset of symptoms, which is characterized by an excessive immune response with further increasing damage to the lungs and the heart muscle. In the last phase there can also be an increase in troponin and BNP as an expression of the cardiac muscle damage and the loss of function of the organ. Diagnostic-therapeutic guidelines from German pulmonologists provide an almost identical assessment of this three-phase course, the early infection, the pulmonary manifestation and the severe hyperinflammatory phase with differentiated therapy recommendations for mechanical ventilation during the individual stages. Severe cases often last for several months, and sometimes the so-called long COVID symptom also occurs.

Known risk groups

According to the Robert Koch Institute, risk groups for severe courses are in particular older people , men, smokers , overweight people, people with trisomy 21 and "people with certain previous illnesses:

• Diseases of the cardiovascular system, e.g. B. coronary artery disease and high blood pressure
• chronic lung diseases, e.g. B. COPD
• chronic kidney and liver disease
• neurological-psychiatric diseases, e.g. B. Dementia
• Diabetes mellitus (diabetes)
• Cancers
• Weakening of the immune system, e.g. B. due to illness or taking medication that weakens the immune system, such as cortisone . "

An evaluation of the English-language and Chinese specialist articles published in mid-February 2020 came to the conclusion that all population groups could be infected. Of those infected, 72% were over 40 years old, 64% were male. 40% of the patients had chronic diseases such as diabetes mellitus and high blood pressure . This is confirmed by the report of the WHO -China joint mission carried out by the WHO in China , which also mentions cardiovascular diseases , chronic respiratory diseases and cancer . According to the RKI's epidemiological bulletin 19/2021, after evaluating around 94,000 cases, the risk of a severe course of COVID-19 disease increases in the presence of certain risk factors: According to this, the five largest risk factors are haemato-oncological diseases (31.5%), metastatic solid tumors with therapy (28.2%), dementia (24.3%), metastatic solid tumors without therapy (23.3%) and heart failure (21.7%).

In addition, the results of the Global Burden of Disease (GBD) study 2019 suggest a statistically significant relationship between the health profile of the world population that existed before the COVID-19 pandemic and the severity of health complications in its further course. In addition, malnutrition and malnutrition and air pollution with regard to higher mortality rates in India are discussed. Air pollution from z. B. Nitrogen oxides or fine particles PM2.5 (fine dust) correlate as risk factors not only with lung diseases, heart attacks, strokes, but also very clearly with severe courses of COVID-19.

However, severe disease courses also occur in younger people and in patients without a previous illness. A report by the Centers for Disease Control and Prevention (CDC) on the age distribution in the United States concluded that severe disease requiring hospitalization or intensive care can occur in adults of all ages. It is true that the elderly are particularly affected, but 20% of those hospitalized and 12% of those receiving intensive care in the collective examined were 20–44 years old. People under 20, on the other hand, showed almost no severe courses.

Social factors

The CDC reported that people of color in the United States are more affected than average. In an analysis of the data up to the beginning of August 2020, the group of "Black or African American People" had a 4.7-fold hospitalization rate and a 2.1-fold death rate. According to an observational cohort study published in The Lancet on April 30, 2021, COVID-19 has disproportionately affected ethnic minorities in the UK . According to Public Health England , an ethnic minority death rate two to four times higher than that of the white population. Possible reasons were a higher prevalence of comorbidities related to poor COVID-19 results (e.g. type 2 diabetes in British South Asians), greater social disadvantage, large multi-generational households and cramped living conditions, differences in occupational exposure risk as well as delayed access to health care.

Children and adolescents

“In children, the disease is usually mild or without symptoms.” A study on children from Wuhan found a confirmed infection in 171 of the 1,391 children examined. Only a minority of the children had a fever or other symptoms. Of the infected children, a 10-month-old infant who also suffered from intussusception died . The study authors rated the results as an indication of a milder course in children and pointed out the possibility of the disease being transmitted through children with few symptoms. Children were also clearly underrepresented in a study in Iceland in which a total of 19,996 people were tested for active infection. An analysis of 2,135 childhood patients in China who were classified as COVID-19 based on a positive test or clinical complaints showed a rate of severe and critical courses of around six percent. These occurred more frequently in infants and children of preschool age.

A South Korean study that the contact tracing of around 60,000 contacts nachvollzog, came to the conclusion that the risk of being infected by a household member aged 10 to 19 years old, was high. The lower rate of infections in households with small and elementary school children was attributed to the school closings during the study period. As a result, the large-scale study showed that the transmission pattern of SARS-CoV-2 is similar to that of other respiratory viruses.

Gender and genetics

According to a meta study from December 2020, men and women contracted COVID-19 about equally often; in men, however, a severe course of the disease was three times more common than in women.

In September 2020, researchers at the Max Planck Institute in Leipzig published a study which, in addition to age and previous illnesses, postulated a genetic factor as a determinant for a severe course of the disease. According to the authors Zeberg and Pääbo, a certain group of genes on chromosome 3 creates a three times higher risk that artificial respiration will be necessary in the course of the disease. It is a gene variant inherited from the Neanderthals . Nothing is yet known about the reason for the correlation between these genes and the course of the disease. At the end of February 2021, a Russian study was published in this context, which makes the nature of the T lymphocytes on the cell surface responsible for the course of the disease in part. The individual genetic makeup of the HLA system plays a fundamental role in the immune response to the virus. Certain alleles of HLA-I seem to be able to detect the virus better and the immune system can react faster. A study of 323 COVID-19 patients found that an increased concentration of perfluorobutanoic acid in the body was correlated with an increased risk of a more severe course of COVID-19 infection.

Pregnant women

With the spread of new COVID variants , the proportion of pregnant women with severe Covid courses has increased significantly. Most pregnant women with severe COVID courses were overweight . The German Society for Perinatal Medicine has registered 2021 2686 pregnant until July 29, which were included in a German hospital with Covid-19th 106 of them had to be treated in an intensive care unit or died. In Great Britain, the corona vaccination has therefore been recommended for all pregnant women since mid-April 2021. On August 11, 2021, the US CDC recommended that pregnant women get vaccinated. The National Vaccination Committee (NIG) of the Republic of Austria recommended COVID vaccination for pregnant women (with MRNA vaccines) on April 27, 2021.

Diagnosis

Case definition and diagnostic procedure

This article or paragraph describes the situation in Germany . Help me to describe the situation in other countries.

The case definitions of the Robert Koch Institute were changed on March 24, 2020, on the website of the Robert Koch Institute you can find a flow diagram on how to deal with suspected COVID-19 cases in the medical field: A flow diagram for citizens has also been made available there , with instructions on how to behave in the event of symptoms of the disease.

Well-founded suspected cases

persons

• with acute respiratory symptoms (symptoms that affect the respiratory tract ; e.g. cough) of any severity and contact with a confirmed COVID-19 case up to a maximum of 14 days before the onset of the disease,
• where clinical or radiological evidence of viruses caused by pneumonia (pneumonia) are present and an epidemic context (several cases of pneumonia) in a nursing home or a hospital is likely to be or suspected

are classified as justified suspected cases by the Robert Koch Institute and reported to the responsible health authorities.

Cases under differential diagnostic work-up

persons

• with acute respiratory symptoms each severity without contact to a confirmed COVID-19 case to a maximum of 14 days prior to onset of the disease, for work in nursing, doctor's office or hospital, or belonging to risk group, or with no known risk factors,
• who have clinical or radiological evidence of viral pneumonia (without an alternative diagnosis ) without contact to a confirmed COVID-19 case,

are classified by the Robert Koch Institute as a case under differential diagnostic clarification and should not be reported initially.

In both cases, a decision is made based on the severity of the disease , risk factors and the environment as to whether outpatient or inpatient care is necessary. In the case of inpatient admission, a laboratory diagnosis is always carried out; in the case of outpatient care, it is part of the differential diagnosis, for people without known risk factors, however, only if the test capacities allow it.

Without technical laboratory procedures (i.e. only on the basis of the symptoms), a differentiation from other viral diseases such as influenza is "difficult to impossible". Other pathogens and diagnoses can also influence the clinical picture (see syndromes , comorbidity and multimorbidity ), for example cold viruses such as rhino , entero and mastadenoviruses , Paramyxoviridae or other coronaviruses . They can be included or excluded through a differential diagnosis with microbiological findings .

Definition: "COVID-19 case"

According to the definition of the World Health Organization (WHO), a COVID-19 case exists if laboratory tests have shown a person to be infected with the SARS-CoV-2 coronavirus - regardless of clinical signs and symptoms - and therefore also if a corona infection is asymptomatic (with no noticeable symptoms). In addition, the WHO also defines the suspected case and the probable case . She points out that these definitions can change in the light of new knowledge and that the member states can adapt the definitions to their particular epidemic situation.

In Germany, COVID-19 cases are transmitted by the health authorities to the Robert Koch Institute (RKI) according to the following case definitions :

1. now no longer applicable : (Clinically-epidemiologically confirmed disease: shows the specific or unspecific clinical picture of a COVID-19 disease without laboratory diagnostic evidence),
2. Disease confirmed by clinical laboratory diagnostics: shows the specific or unspecific clinical picture of a COVID-19 disease and has been proven by laboratory diagnostics,
3. Infection confirmed by laboratory diagnostics and the clinical picture not met: has been confirmed by laboratory diagnostics and the clinical picture is known, but does not correspond to the specific or unspecific clinical picture of a COVID-19 disease, e.g. B. asymptomatic infections,
4. Infection confirmed by laboratory diagnostics if the clinical picture is unknown or not fulfilled: was detected by laboratory diagnostics, but the clinical picture was not recorded, could not be determined or there were no symptoms.

Cases in category 1 are well- founded suspected cases , cases in categories 2 to 4 are laboratory-confirmed COVID-19 cases and are published jointly by the Robert Koch Institute as case numbers; for information on the obligation to notify, see the section on mandatory reporting, ICD-10 classification, occupational disease . This RKI reference definition corresponds to the WHO case definition.

The COVID-19 deaths include people who died immediately of a COVID-19 disease, as well as those infected with corona with previous illnesses for whom the exact cause of death cannot be conclusively proven.

Laboratory diagnostic evidence

→ Main article : Corona test

PCR report from the Technical University of Munich (October 2020)

According to the RKI, the laboratory diagnostic, direct pathogen detection is carried out by nucleic acid detection (e.g. RT-PCR, real-time quantitative reverse transcriptase-polymerase chain reaction ). It is also possible to isolate the pathogen in a cell culture , but the WHO does not recommend it for routine diagnostics. ( See also: → Section: Virus and Antibody Detection )

The virus can be detected directly in the sputum , in the tracheal secretion , in the bronchoalveolar irrigation fluid and in the nasopharynx swab as well as in the stool . In Germany, the laboratory test was carried out for the first time by the consulting laboratory for coronaviruses at the Charité in Berlin, and numerous other laboratories in Germany are now able to do this.

If the result is positive, there is now a laboratory-confirmed COVID-19 case . If the result is negative, but there is a persistently high suspicion of infection with SARS-CoV-2, it is recommended to repeat the diagnosis. First experiences with COVID-19 from China showed that just at the beginning of the infection only about 70% of the patients were positive in the RT-PCR test, while it was a total of 94% after the second test.

The blood serum of affected persons should be kept for indirect evidence ( antibody detection ) . (As of April 13, 2020)

RT-PCR test

Play media file

How the PCR test works

→ Main article : SARS-CoV-2 section RT-PCR

The detection method is the real-time quantitative reverse transcriptase polymerase chain reaction , also known as qRT-PCR, RT-qPCR or just as a PCR test for short. It is based on the detection of two nucleotide sequences , referred to as the E gene and the RdRp gene. A positive PCR test is not synonymous with infectivity : With the recommended smear technique, the PCR test is always positive for longer than viruses capable of replication are detectable. A high Ct value (> 30) in this case, among other things, indicates a low viral load and thus low infectivity, which can be an argument for being released from quarantine. However, it must also be noted that at the beginning of the infection, the viral load is also low and the Ct value is high, so that the patient can become highly contagious in a few days.

Location of the nasopharynx (nasopharynx) and oropharynx (mouth pharynx)

The probability of correctly recognizing a patient as infected with the help of the RT-PCR test depends largely on the type of material taken (for the difference between “infected” and “infection”, see there ). In a small Chinese study in 205 patients , the nasal swab , which is mostly used because of its ease of execution, showed a sensitivity of 63%. Evidence from the bronchoalveolar lavage (bronchoalveolar lavage, BAL) recognized the virus in 93% of cases. In a few patients, evidence of a systemic infection was also found in the blood , an infection in which the pathogens spread through the bloodstream through an entire organ system or the entire organism.

A Chinese study of 1,014 patients with lung disease during the outbreak of the epidemic in Wuhan showed that positive computed tomograms (CTs) ( compatible with COVID-19) were detected in around 88% of patients and only 59% using the PCR test. Of the 413 people who tested negative with RT-PCR, 75% then had positive CT results. The result of the study was that CTs are suitable as a primary tool for the reliable detection of COVID-19 and have a higher diagnostic sensitivity than an RT-PCR test.

It is therefore important for samples of the upper respiratory tract a swab of the nasal pharynx ( nasopharynx ) or the oropharynx oropharynx (see figure) to take. If possible, this should be supplemented with a sample of the lower respiratory tract (bronchoalveolar lavage, sputum, tracheal secretion ). The PCR test performed with throat swabs is only reliable in the first week. The virus can then disappear in the throat, while it continues to multiply in the lungs (contrary to popular belief, the virus does not “migrate” into the lungs, but is transported with each breath with the inhaled droplets containing the pathogen into the entire respiratory tract, where they are can stick to any mucous membrane, the virus or fragments of it are only no longer detectable in the throat because the lymphatic pharynx ring, as part of the lymphatic system, has fulfilled its task as a defense barrier of the upper respiratory tract). In infected people who are tested in the second week of the disease, the PCR test based on the throat swab is not reliably positive or not reliably negative in relation to the overall status. Alternatively, sample material can then be taken from the deep airways using a suction catheter or coughed up material (sputum) can be used. In addition to errors in sampling, false negative results can occur due to insufficient viral load in the sample material, the test kit or its use. The sensitivity of the smear test depends on the time after exposure to the pathogen. Around 40% of patients test on the day the symptoms start . On the eighth day after exposure , the best sensitivity was found at around 80%.

Antibody test

Lateral flow test for antibody detection IgG and IgM ; left test kit: negative result; Right test kit: positive result

→ Main article : Corona test # Antibody tests

The virus can also be identified by genome analysis ( RNA sequencing of the genome ). The NAAT ( Nucleic Acid Amplification Technology ) method is also based on RT-PCR; however, the assembled assay is easier to handle and can be used by appropriately equipped routine laboratories. Such an assay (test kit) called Centers for Disease Control and Prevention (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT) -PCR Diagnostic Panel has been available since February 2020 .

The detection of antibodies as a serological survey was developed by specifying the WHO since mid-January 2020th In a study previously only published as a preprint in April 2020, three commercial ELISA tests and six commercial lateral flow tests were evaluated. For the three ELISA tests, the diagnostic sensitivity (true-positive rate) was between 67% and 93%, the specificity (true-negative rate) was between 93% and 100%. There were false positive results due to cross-reactivity with serum samples that contained antibodies against other coronaviruses (e.g. human coronavirus HKU1) and other viruses. For more details, see the Antibody Detection section in the virus article.

Rapid antigen tests

Rapid antigen tests that respond to SARS-CoV-2 proteins have been available since autumn 2020 . Like PCR tests, they are usually performed on material obtained in nasopharyngeal swabs. The sensitivity of these tests is lower than that of PCR tests, which are used as the reference method. The advantage is that the test takes less than 15 to 30 minutes, and some of the tests can be carried out on site. A study published in advance in November compared seven antigen tests with PCR tests and described that the sensitivity of the tests coincided with virus concentrations that would typically be observed in the first week with symptoms, which in most patients would correspond to the time of infectivity. According to the Robert Koch Institute , a positive test result must be retested using PCR to avoid false-positive results. A negative result in the antigen test does not rule out infection, especially if there is a low viral load, such as B. in the early incubation phase or from the second week after the onset of symptoms or in the late phase of the infection.

As an alternative, the PCR pool tests, which are considerably more sensitive than rapid antigen tests and also associated with a lower risk of exposure when taking samples, are being discussed. The sample swabs are sucked for 30 seconds (coll .: lollipop test). Then the swabs are z. B. all students in a school class are brought together in a single sample container (pool) and then collectively subjected to a PCR test (PCR pool test). In the event of a positive result, all students in the affected classes are then individually tested using PCR in order to identify the infected students.

Imaging procedures

HRCT of a 38-year-old with typical lung changes

HRCT of a 50-year-old woman with rapidly progressing disease

Imaging cannot tell whether a person is infected with the virus. However, in patients whose disease is so severe that it causes pneumonia, this can be detected by imaging. In the imaging, the CT shows frosted-glass-like thickenings, as they also occur in other viral pneumonia. These changes can also be shown sonographically because they are often close to the pleurus.

Some scientists are of the opinion that the diagnosis of COVID-19-typical lung damage by means of imaging is superior to diagnosis by RT-PCR, since the CT imaging can be done faster and the changes are detected more reliably than with the more error-prone swab test. Radiologists from Changsha reported from a case series of 167 patients on five patients in whom the RT-PCR for the virus was negative at the time of pneumonia confirmed by computed tomography and the virus was only detected after repeated tests during the course of the disease. In times of an epidemic, as a triage strategy in the case of a high number of patients, it can be useful to treat suspected cases with typical imaging even with negative RT-PCR such as COVID-19 cases in order not to delay the initiation of therapy.

Treatment options

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Treatment of people with COVID-19 in East Timor

In a preliminary published, randomized study, the nucleoside analogue remdesivir showed a reduction in the duration of illness in hospitalized patients. The drug is approved in the EU for COVID-19 patients who require oxygen.As the benefits of the drug could not be confirmed in further studies, remdesivir is not recommended according to the current guideline of the European Respiratory Society (ERS). The interdisciplinary guideline of the under the leadership of DIVI advises against the use in patients without oxygen requirement and invasively ventilated patients. In the case of patients receiving oxygen without invasive ventilation, no recommendation for or against the drug is given based on the available data.

In mid-July 2020, the British study group RECOVERY published preliminary study data, according to which dexamethasone reduced the death rate in patients on ventilators from 41% to 29%, for patients with oxygen supply from 26% to 23%. Treatment with dexamethasone had no beneficial effects in patients who did not need oxygen. Dexamethasone slows the excessive reaction of the immune system, the cytokine storm . The RKI recommends the use of dexamethasone in all forms of oxygen dependency, regardless of whether there is an invasive or non-invasive ventilation therapy. Use in the early course of the disease is not recommended due to the possibility of a worsening prognosis.

Due to the increased risk of thrombosis and pulmonary embolism in COVID patients, anticoagulation (blood coagulation inhibition) using low-molecular or unfractionated heparin is recommended for all hospital-compulsory COVID patients over the entire course of the disease. This should be initiated as soon as possible after admission. Anticoagulant therapy at the full therapeutic dose is recommended in all hospitalized patients with risk factors for a thrombotic event. In the event of a deterioration in compulsory intensive care, however, once a thrombosis has been ruled out, this should be reduced to a prophylactic dose. There is no recommendation for routine anticoagulation for outpatients.

Chloroquine and hydroxychloroquine initially showed promising results in in vitro studies in cell culture . The further investigation of hydroxychloroquine was stopped in the SOLIDARITY study because there was no evidence of its effectiveness. The US Food and Drug Administration withdrew its emergency approval of the drug for COVID-19 in June 2020. In the animal model, the different times of treatment showed no influence on the viral load, the time until the virus was removed from the organism or a protective effect against the infection. No effect could be demonstrated on lung epithelial cells in culture. Even in Vero cells in which TMPRSS2 was genetically engineered, no prevention of the infection could be demonstrated. In two comparative studies with a total of more than 5000 hospitalized participants, a slightly higher mortality rate was observed in groups treated with hydroxychloroquine than in control groups. The RKI explicitly advises against the use of chloroquine and hydroxychloroquine outside of clinical studies.

Tocilizumab , a monoclonal antibody approved for the treatment of various forms of rheumatoid arthritis and cytokine release syndrome , among other things , was tested for its effectiveness against COVID-19. There was no influence on mortality or clinical condition. However, there were indications of a reduction in the risk of requiring ventilation. On the basis of the available data, the RKI recommends its use, if possible, only in the context of clinical studies. Off-label use in the hyperinflammatory phase of the disease is possible. The ERS recommends the use of tocilizumab and other drugs of this substance class in patients whose breathing has to be supported by oxygen or ventilation.

In November 2020, the monoclonal antibody Bamlanivimab ( Lilly ) received emergency approval in the USA for the treatment of mild to moderate disease if there is a high risk of severe disease due to previous illnesses or age. The DIVI guideline states that it can be used in early hospitalized patients without respiratory symptoms with at least one risk factor for a severe course. There is no evidence of benefit for patients with an advanced course.

Antibody-rich plasma from recovered patients seems suitable for treating acute cases, but can only prove success in the early phase of the disease. So far there is no approval for the use of convalescent plasma. However, there is evidence of a possible beneficial clinical effect and lower mortality in patients with severe disease. Earlier virus elimination is also achieved. The RKI recommends the use of convalescent plasma as part of controlled clinical studies or individual healing attempts in consultation with an experienced center. According to the DIVI guideline, convalescent plasma should not be used in hospital patients. Based on the data, it is unclear whether some patient groups could benefit from this.

In patients who develop acute lung failure due to viral pneumonia , the usual principles of ventilation therapy for viral pneumonia apply. The gas exchange can be ensured by non-invasive ventilation or by invasive ventilation after intubation . Conservative volume therapy is recommended to avoid overhydration of the patient and the risk of additional pulmonary edema . As part of the extended hemodynamic monitoring, the blood flow should be continuously monitored and, if possible, the extravascular lung water determined. Non-invasive ventilation using high-volume oxygen carries the risk of aerosolization of the virus and thus an increased risk of infection for the staff working on the patient.

The DIVI guideline gives a weak recommendation for the early use of the anti-virus antibody drug casirivimab / imdevimab in hospitalized patients who have not yet developed measurable IgG antibodies against the virus. The RKI guideline also sees potential in the use of outpatients with risk factors for a severe course.

Whether vitamin D is suitable for the treatment of acute COVID-19 disease is still being researched (as of February 2021). According to health authorities z. B. in the USA, England and Germany as well as a Cochrane meta-analysis there is currently insufficient evidence for this .

The early inhalation of powdered budesonide in high doses was able to prove in a study a reduction in the duration of the illness and a lowering of the likelihood of hospital admission. However, this has not yet been reproduced. Due to the available data, the COVRIIN specialist group at the RKI advises against using the drug in COVID-19. The guideline of the US-American NIH assesses the data situation as insufficient to give a recommendation for or against the use of the drug.

Prospect of healing

Percentage of infected and deceased persons per age (blue curve) - meta-study at the end of 2020
based on 27 individual studies, with 95% prediction interval (gray)

Assessment of the risk of death

There are three different metrics to describe the risk of death from the disease:

• The infected-deceased percentage (IFR) describes the percentage of those who died of the disease in relation to the total number of all infected. This proportion can be approached through estimates. Depending on the country or region, the estimates of the proportion of infected and deceased people vary depending on various country-specific parameters, such as: B. the performance of the health system, the age structure of the population or differing sampling methods.

The proportion of infected and deceased increases exponentially with age , from 0.002% at 10 years of age, 0.01% at 25 years of age, 0.4% at 55 years of age, 1.4% at 65 years of age, 4.6% at 75 years of age , 15% at 85 years of age, and more than 25% at 90 years of age or older, according to a meta-analysis based on 27 individual studies from December 2020 (see figure). According to this, COVID-19 is still more dangerous than the risk of a car accident, even for middle-aged people. Targeted measures to contain infections in the elderly could significantly reduce the number of deaths.

In July 2021, the RKI estimated the number of infected and deceased people in Germany to be around 0.4-0.6% based on the registration data and the number of unreported cases determined by studies .

Mortality also depends on the availability of beds in hospitals and intensive care units.

A systematic review and meta-analysis from September 2020, including 111 studies from industrialized countries ( OECD members) , estimated the proportion of infected and deceased across different populations to be 0.68% (95% confidence interval [0.53-0.82%) ]). This could vary significantly in the population according to age and underlying pre-existing diseases; Likewise, the risk of death due to failure to report deaths could be underestimated.

• The proportion of cases deceased (CFR) refers to the number of deceased reported cases divided by the total number of reported cases. As a result, this number is heavily dependent on the efficiency of the diagnostic and reporting system and can both overestimate and underestimate the actual lethality.

An estimate by the ECDC at the end of April 2020 assumed a case-deceased share of 10.5% for the whole of Europe . The RKI stated the proportion of deceased cases based on the German registration data up to the beginning of June 2021 as 2.4%; the RKI stated the proportion of deceased among the symptomatically ill persons recorded in the reporting system as 6.2%.

• The symptomatic case-deceased percentage (sCFR) is the percentage of infected people who show symptoms and who die in the course of their infection. This proportion is clinically relevant for assessing the prognosis of the requirements for the health care system. According to the Robert Koch Institute, no reliable statement can be made about the actual number of sick people. There are various ways of estimating this proportion.

Risk of hospital admission vs. 40-44 year olds (dark blue),
adjusted for previous illnesses (light blue), with 95% confidence levels (gray)

Estimation of the risk of hospitalization

The risk of being admitted to hospital due to COVID-19 increases, especially with older age, five-fold compared to 40-44 year olds (see figure). In addition to age, pre-existing conditions such as Down's syndrome , intellectual disability, kidney transplantation, lung transplantation, kidney failure with dialysis and lung cancer increase the risk three to seven times, according to a study from September 2021 based on the 66 million inhabitants of France.

State of research on long-term effects

→ Main article : Long COVID

From the radiological findings of a case report, Taiwanese doctors have concluded that, as with SARS, long-term effects on the lungs in the form of fibrotic changes are possible. Due to a case of viral encephalitis caused by SARS-CoV-2 and the experience with other coronaviruses, researchers from Beijing are raising the possibility of long-term persistence of the virus in nerve cells, which could lead to neurological sequelae. A review of COVID-19 and its involvement in the heart by US doctors considers the possibility of cardiac-related long-term effects, drawing on experience with SARS and an Italian case report of fatal myocardial inflammation after the disease has healed. In a study on 100 patients, a majority of the patients showed a measurable inflammation of the heart muscle in the magnetic resonance tomography even after symptomatic healing of COVID-19. Because of the small study group and the type of selection of those examined, it is unclear to what extent these patients are representative of the total number of diseases.

A study of 384 people discharged from the hospital found a high rate of patients who continued to have symptoms around two months after discharge. More than half complained of tiredness, around half of shortness of breath and around a third of persistent coughing. In around a third, a blood test found increased D-dimer values, a consequence of blood clotting and subsequent fibrinolysis (clot dissolution). In 38% there were abnormal X-ray findings, in 9% they were worse than at the time of discharge.

As with other infectious diseases with pneumonia , recovery can take a long time. After an acute illness, symptoms may persist or appear weeks or months later. In addition to organ-specific long-term consequences that result from the treatment of a serious illness, long-term symptoms of fatigue, memory and word-finding disorders , dizziness and nausea are also observed with milder courses. Data from England indicate that around 40% of hospital patients need long-term medical help and around 10% of those not treated in hospital have symptoms for more than four weeks. According to a study by researchers at University College London , symptoms lasted longer than 12 weeks in around 2% of those suffering from Covid-19.

immunity

A previous infection with SARS-CoV-2 induces an immune response against the virus. Antibodies of various classes can be detected on average around two weeks after the onset of the complaint. These include antibodies against the spike protein and also the nucleocapsid of the virus. Around a tenth of those infected do not form any measurable antibodies. The level of the antibody correlates with the severity of the disease. T cells and B cells that are reactive against the spike protein can also be detected. These parameters can still be detected around six to eight months after the disease, with the amount of antibodies falling rapidly. It is still unclear to what extent these parameters provide protection against infection or serious illness. Antibodies that neutralize the virus in laboratory tests have been linked to protection against a serious illness. A threshold value above which they protect against serious illness or infection has not yet been established. Re-infection after infection is possible. This is to be differentiated from people in whom genetic material of the virus can be detected for longer after the illness. The CDC states that the duration of the immunity is still unclear, but does not recommend a new test for the genetic material of the virus three months after a confirmed infection. The ECDC classifies the data in such a way that an infection protection effect of 81-100% over a period of five to seven months has been proven.

On the basis of the data from the German reporting system, the RKI reports that reported re-infections are rare events. However, based on experience with other coronaviruses, it is conceivable that undiagnosed re-infections might not be unusual.

An early formation of virus-reactive T cells seems to correlate with a mild course of the disease. In contrast, disturbances in B-cell maturation were observed in severe courses. In laboratory tests, cross-reactivities between other coronaviruses occurring in humans could be demonstrated both at the antibody level and the cellular immune response. The study situation as to the extent to which this influences the likelihood of infection or the course of the disease is contradicting itself.

prevention

Individual hygiene measures

Measure during the COVID-19 pandemic

Right and wrong sneezing and coughing

The Robert Koch Institute (RKI) published on 28 January 2020 recommendations how individuals and others from infection can protect with SARS-CoV-2:

• Everyone should take care of thorough hand hygiene. First and foremost, this requires regular hand washing , at least 20 seconds, and with soap. Hands should be washed at least when coming home, before and after eating, before and after contact with other people, after using the toilet and after sneezing or coughing.
• Wearing a face mask or an everyday mask in public.
• Hands should be disinfected with a suitable disinfectant after contact with surfaces that may be virally contaminated, such as handle elements in public transport or shopping trolleys in supermarkets .
• Other people should be kept at least 1.5 to 2 meters away. In principle, direct body contact, such as shaking hands , kissing or similarly intensive body contact, as well as large crowds should be avoided.
• Since a distance of only two meters is usually not sufficient during sport and when moving in public in order to prevent infection by droplet infection , care should be taken to ensure that the distance to others is greater; this is especially true when you are in the slipstream of someone else.
• When singing or making music with wind instruments, a minimum distance of three meters should be maintained.
• Coughing or sneezing should be done in the crook of your arm, never in your hand.
• If several people are present, closed rooms must be ventilated every 20 minutes by means of five-minute burst ventilation . Ventilation units with a HEPA filter H14 (degree of separation> 99.995 percent) are recommended.

The indoor air quality can also be monitored with the help of carbon dioxide measurements. The mean content of carbon dioxide enriched by the exhaled air should on average not be higher than 1000 parts per million and can be determined and displayed, for example, with the aid of CO ₂ lights .

The World Health Organization (WHO) also recommends:

• Do not touch your eyes, nose, or mouth with unwashed hands;
• staying at home if you or a roommate feel sick - even if you have mild symptoms (such as a runny nose or headache );
• If you have symptoms of illness, never go to a practice or hospital in person , but rather call them beforehand to follow further instructions.

If you have symptoms or complaints that could indicate an infection with the coronavirus, you should first call your doctor ; Outside the opening times of the family doctor's practice, the on- call medical service can be called in Germany : »Telephone number: 116 117 «. You should also isolate yourself at home so as not to infect other people. In acute emergencies, the emergency number : »Number: 112 « should be called. The German Federal Ministry of Health warns that nobody should forego medical treatment for fear of being infected with SARS-CoV-2 (“Coronavirus”) in the event of severe symptoms: B. imagine having an acute heart attack. Especially with a heart attack, every minute counts. The chances of dying of a heart attack are high if you don't report in time. The likelihood of contracting the coronavirus [at the doctor's or in the hospital] is low. "

The Federal Center for Health Education recommends turning away from other people immediately when coughing, sneezing or blowing your nose and, if possible , sneezing / coughing into a handkerchief , which must then be disposed of immediately, and then wash your hands thoroughly.

In the course of 2020, several Corona apps were developed that serve to understand chains of infection. In Germany, this is the Corona warning app , the use of which is strongly recommended by the RKI.

Christian Drosten recommended reducing social contacts to a large extent, especially in the days before a family get-together with older people, by avoiding meetings or working in the home office (“pre-quarantine”), for example.

In view of the impending third wave in Germany, the RKI issued updated recommendations for everyday life on March 31, 2021. The following were emphasized in the form of eight "tips":

• the Social Distancing also observe when visiting friends;
• meet better outdoors rather than indoors;
• in the event of an indoor meeting, keep your distance, wear a mask and ventilate regularly: open the windows wide for 5 minutes every 20 minutes;
• refrain from leisure travel;
• stay at home if symptoms occur and seek medical advice;
• if the PCR, rapid or self-test is positive, inform all recently met people; also have a positive rapid test or self-test checked with a PCR test;
• Adhere to the AHA + L rules (distance, hygiene, wearing a mask in everyday life, ventilation) even if the quick test or self-test is negative;
• accept an offered vaccination.

WHO study, June 2020

A study commissioned by the WHO systematically examined the optimal use of the protective measures mentioned. An international team of researchers has investigated for the first time how physical distance, face masks and eye protection affect the spread of COVID-19. The search resulted in 172 observational studies in 16 countries and six continents without randomized controlled trials and 44 relevant comparative studies in health care and outside of the health care system (n = 25,697 patients). Virus transmission was less at a physical distance of 1 meter or more than at a distance of less than 1 meter, and protection increased as the distance increased. The use of face masks can lead to a strong reduction in the risk of infection with stronger associations with N95 or similar respiratory protection masks (FFP2) compared to surgical disposable masks or similar, e.g. reusable masks. The results of this systematic review and meta-analysis support physical distancing of 1 meter or more and provide quantitative estimates for models and contact traces to inform policy makers.

For example, the risk of infection for people standing more than a meter away from the infected person was 3 percent compared to 13 percent at a distance of one meter. With every additional meter (up to 3 meters) the risk was halved again. A physical distance of more than 1 meter in both healthcare and society reduces the risk of infection by 82 percent. With eye protection, the risk of infection or transmission was 6 percent compared to 16 percent without eye protection. For eye protection, the researchers determined an overall protective effect of 78 percent. According to the study, mouth and nose protection reduces the risk of infection by 85 percent. Particle-filtering masks such as N95 (for example “gauze masks” or reusable masks with 12 to 16 layers of cotton) could possibly offer workers in health care facilities better protection than surgical masks. Cotton masks are also suitable for the population. In a sub-analysis, these achieved a protective effect of 96 percent. However, none of these interventions, even when properly used and combined, offer complete protection against infection.

Surface cleaning and disinfection

Disinfection on a street in East Timor

Since the surfactants usually contained in soap and cleaning agents destroy the fatty layer of coronaviruses, these surfactants are sufficient in everyday life to largely rid hands and other surfaces of pathogens. Routine surface disinfection in domestic and public areas is not recommended by the RKI; Any disinfection required in individual cases should be carried out as a wipe and not as a spray disinfection, as the latter is less effective and the disinfectant can be inhaled. For reasons of fire protection, alcohol-based products should only be used on small areas.

Protective mask as a means of prevention

→ Main articles : Everyday mask  and mouth and nose protection

An experimental study from 2008 concluded that any type of everyday mask may reduce virus exposure, even if it is improperly fitted or improvised . The authors conclude that the general wearing of masks by the population could reduce the transmission of respiratory diseases.

In East Asia, the use of masks for the general population is considered a key element of prevention. In March 2020, Hong Kong doctors recommended that other countries introduce this practice as well. The US CDC , referring to the current study situation, recommended that all citizens cover their mouth and nose in public. The Lancet magazine has compiled an overview of the use and assessment of face masks in various countries .

Although the effectiveness of a mouth and nose covering as a general hygiene measure is hardly questioned, the scientific data situation with randomized comparative studies that statistically unequivocally prove this for SARS-CoV-2 has so far been rather poor.

A meta-analysis provisionally published in April 2020 by an international research group came to the conclusion that wearing face-to-face masks could significantly reduce the transmission of respiratory diseases and the spread of respiratory infections by health workers, but also among the general public. The authors of the study explicitly advocated protection with masks in order to prevent or at least hinder the transmission of respiratory viruses and thus the spread of respiratory diseases.

For optimal effectiveness it is important that the mouth and nose cover fits correctly, i.e. H. It is worn close-fitting, is changed when it is wet and that no (unconscious) manipulations are carried out on it while it is being worn. According to the WHO, however, wearing a mask in situations in which this is not recommended can create a false sense of security, as a result of which central hygiene measures such as good hand hygiene can be neglected.

A distinction must be made between the protection of the wearer (self-protection) and the protection of the environment (external protection). Masks with an exhalation valve protect the wearer, but not the environment. (For this difference, depending on the mask type, see the table here and the graphic here .)

The Federal Institute for Drugs and Medical Devices points out that everyday masks (in contrast to medical face mask and respiratory protection masks ) are not standardized and therefore an adequate protective effect against the transmission of SARS-CoV-2 cannot be guaranteed. Accordingly, wearers cannot rely on the fact that they or others are protected from transmission of the pathogen by wearing such masks, and must continue to observe the rules of distance.

In November 2020, the Society for Virology and the German Society for Hygiene and Microbiology published summarized recommendations for action as S1 guidelines on the topic of infection prevention through the wearing of masks in connection with COVID-19.

Virucidal gargle and virucidal nasal spray

The German Society for Hospital Hygiene recommends a virucidal gargle and virucidal nasal spray in order to "reduce the viral load at the entry points, since the likelihood of infection increases with exposure and the initial viral load influences the severity of the infection". Studies that prove an influence on the frequency of the disease or its course are not yet available.

Infrastructural minimization of the droplet and aerosol transfer ("source control")

Transmission and spread of virus-infected aerosols through aerosol and droplet infection can be suspected, especially in closed rooms . In addition, air currents caused by air conditioning can contribute to the spread of pathogens. By means of a spatial analysis of the droplet and aerosol transport, suitable infrastructural measures can be planned and implemented in order to minimize the exposure of non-infected people indoors.

Waste disposal

Although no cases are known so far in which people were infected with the SARS-CoV-2 virus through contact with contaminated surfaces, this path of infection cannot be ruled out. In order to protect caretakers, residents of apartment buildings and waste disposal employees, the Federal Environment Ministry has therefore named precautionary measures: In households with infected people or with justified suspicions, there is no obligation to separate waste. In addition to residual waste, these households also have to dispose of packaging waste, waste paper and organic waste in the residual waste intended for incineration. The waste must not be thrown loose in the bin, but securely packed in sturdy, tear-resistant rubbish bags. Only after recovery and the end of the quarantine should the separate disposal of glass waste, deposit packaging, electrical and electronic waste, batteries and pollutants be addressed.

The guidelines on waste disposal in the coronavirus crisis published by the EU Commission on April 14, 2020 contain further principles in the case of the treatment of sick people in private households: handkerchiefs and breathing masks should be collected in a separate waste container in the patient's room, gloves and face masks from supervisors in a second container near the door. The rubbish bags must be closed before they are transported out of the patient's room, but can then be collected together and disposed of with the residual waste.

Prophylactic increase in vitamin D levels

A connection between a low vitamin D level and the severity of COVID-19 disease is discussed in the literature. According to health authorities from the USA, England or Germany, there is currently (February 2021) no evidence of vitamin D administration to prevent COVID-19. According to the Federal Institute for Risk Assessment , based on the current study situation, there is no reason to recommend the general intake of dietary supplements with vitamin D to the healthy general population, but for residents of nursing homes a general vitamin D intake of up to 20 µg (800 IU) per Day to be considered.

Medical staff

Particle filtering FFP2 half masks. Due to the exhalation valve, there is only self-protection, but no third-party protection.

The Robert Koch Institute announced on January 24, 2020 the first evidence that hygiene measures are necessary to prevent transmission of the virus through droplets on medical staff: was the consistent compliance with the recommendation as basic hygiene , especially hand hygiene, called. With the change in the case definitions on February 14, 2020, the hygiene measures were specified and subsequently adapted to new findings (as of April 8, 2020): For reasons of patient protection during the pandemic, “the general wearing of oral and Nose protection (MNS) recommended by all personnel in direct contact with particularly endangered groups of people. When treating and caring for patients with possible or confirmed SARS-CoV-2 infection, personal protective equipment (PPE) should be worn in the form of a protective gown, protective gloves , protective goggles and at least a tight-fitting MNS or a respirator . A mask of the FFP2 standard , which offers protection against aerosols and droplets, should preferably be used . If FFP2 masks are not available, at least one MNS should be worn as protection against droplets. For all activities that involve aerosol production (e.g. intubation or bronchoscopy), FFP2 masks or additional respiratory protection are recommended. This information also applies to inpatient care.

If there are no CE-marked masks available, according to the Federal Institute for Occupational Safety and Health (BAuA), masks that at least comply with the NIOSH standard N95 (as of April 6, 2020) can be used "until further notice" .

In the event of symptoms of a respiratory disease, the patient must wear mouth and nose protection and, if possible, is taken to a separate room in the doctor's practice, where further examinations take place.

For the chemical disinfection of hands and surfaces, disinfectants are suitable that cover the areas of activity "limited virucidal", "limited virucidal PLUS" or "virucidal". An evaluation of 22 studies that deal with the persistence and inactivation of medically relevant coronaviruses (such as SARS-CoV and MERS-CoV) in health facilities, among others, shows that ethanol- based agents (at least 65%) are used for surface disinfection. , Hydrogen peroxide or sodium hypochlorite are effective in appropriate concentrations.

In addition to the hygiene measures carried out by the medical staff, the preventive measures also include the accommodation of the patient in an isolation room with an anteroom or lock and the shutting down of any ventilation systems that may be present so that air can be exchanged with other rooms.

Dental treatment

For dental treatment, drilling instruments with water cooling are usually used. This forms an aerosol . A possible transmission through this form of aerosol has not yet been scientifically proven, since in dental practices, unlike in laboratory tests, extensive suction is used. Previous studies on the amount of virus in aerosol did not use the saliva of a symptom-free infected person as a test substrate (real scenario), but highly contaminated, artificial reagents that were similar to a 1 ml throat swab of a patient with a severe course. Information from the dental clinic of the University of Wuhan refutes an increased risk of transmission for dental staff if the previous hygiene measures are observed (mouth and nose protection, protective goggles, examination gloves).

In March 2020, the necessary protective equipment for the treatment of patients proven to be infected with COVID-19 (respiratory mask FFP2, protective goggles with side protection or visor, examination gloves, long-sleeved protective gown, hood) was not available or only to a limited extent in many dental practices - also due to delivery problems . Patients should therefore only see a dentist in emergencies and urgent treatments. In May, the German Dental Association stated that the situation in the field of protective equipment had improved and that the hygiene standards had been adapted to the pandemic situation. So all dental treatments could be done again. The German Dental Association provides extensive up-to-date information on its website.

Wastes from medical treatment

The RKI recommendations on waste disposal as part of the treatment and care of patients with an infection by SARS-CoV-2 are based on Communication 18 of the Federal / State Working Group on Waste (LAGA). They are regularly adapted to new findings. As far as we know today (as of April 24, 2020), the treatment of COVID-19 patients generally does not generate any hazardous waste . If the usual occupational safety measures are observed and suitable personal protective equipment is worn, non-liquid waste from the treatment of sick patients does not pose a particular risk of infection. The waste must be collected in tear-proof, moisture-proof and leak-proof containers immediately at the point of origin and transported in securely closed containers without being refilled or sorted. Pointed and sharp objects should be placed in break-proof and puncture-proof disposable containers. Waste that is generated during the microbiological and virological diagnosis of COVID-19 and that cannot be disinfected using a recognized process, on the other hand, is usually considered to be infectious under waste code 180103 *. From an infection prevention point of view, special requirements apply to their collection and disposal.

Social prevention

See also : pandemic prevention

See also : spatial distancing

Strategy to ensure the medical care of patients with severe disease by slowing down the spread of the Sars-CoV-2 epidemic with the help of protective measures . If the capacity is exceeded, triage must be introduced.

Like all measures to combat pandemics, social prevention has the following goals:

1. Reducing the morbidity and mortality population
2. Ensuring the care of sick people
3. Maintaining essential public services

These overarching goals are achieved through different strategies depending on the epidemiological phase. As long as most cases emerge in isolation or in local clusters, the focus will be on containment. For this purpose, sick people must be isolated and contact persons identified as completely as possible and placed in (domestic) quarantine. This is intended to interrupt chains of infection as quickly as possible. If human-to-human transmission continues, the European Center for Disease Prevention and Control recommends a number of other non-pharmaceutical measures to contain COVID-19:

1. Individual hygiene measures such as hand and respiratory hygiene and the use of face masks wherever sufficient spatial distance cannot be maintained;
2. environmental measures such as cleaning of surfaces and ventilation of enclosed spaces;
3. population- related measures such as spatial distancing , restrictions on travel and mobility and restriction of the meeting of different people.

The ECDC closes after evaluation of scientific studies have shown that non-pharmaceutical measures proved a critical role in mitigating the COVID-19 pandemic have played in Europe. They remain necessary as long as no vaccine is available. Because of the serious negative social consequences of the measures, they should only be used where the local epidemic situation makes it necessary. Three systematic reviews in the context of the Cochrane Library on travel restrictions, mass testing and quarantine of contact persons determine that none of these measures alone has a large demonstrable effect on the spread of COVID-19. After all, there is evidence of the effectiveness of travel restrictions, and recognizable evidence of the effectiveness of quarantines. The authors conclude that the measures examined should be used in combination with other non-pharmaceutical measures. Measures such as face masks and social distancing therefore remain important to control the COVID-19 pandemic.

A meta-study published in June 2021 in the Journal of Infection came to the overall result based on 34 studies that early implementation of measures is crucial, not rigor. Closing schools, workplaces, shops and venues and banning public events are most effective. The wearing of masks and public information campaigns are also effective, and the latter also have the advantage of requiring less interference in people's lives. On the other hand, there is no evidence of the effectiveness of the closure of public transport, of test and contact tracing strategies and quarantine measures. Long indoor gatherings with poor ventilation should be avoided, as this could lead to super spreaders - a common feature of coronaviruses. A lifting of measures should be carried out carefully, adapted to the environment, also with adapted containment measures, gradual opening and respective monitoring of their effects on the population.

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  The sidewalks in Farnham , Surrey have been widened with the loss of a lane to allow social distancing.

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  No visits sign in the Munich Clinic Bogenhausen

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  Distance control in a theater in Kavala / Greece

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  Urinals that were blocked to keep your distance during the pandemic

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  Admission requirements at the entrance to an Irish pub in Hamburg-Harburg , July 2021

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  Transparent curtains as "room dividers" in gastronomy

Contact person management by public authorities

Three methods to check in for contact tracing

The follow-up of contact persons takes place within the scope of infection protection in accordance with the assessment of the situation by the locally responsible health department . The Robert Koch Institute differentiates between contact persons with a higher risk of infection (category I), contact persons with a lower risk of infection (category II) and contact persons of category III, which are medical personnel with a low risk of exposure. A higher risk of infection according to Category I can arise through close contact, contact with the secretions of the infected person or a contact situation with a high risk of transmission through aerosols.

In Germany, people in Category I, after weighing up the possibilities and following a risk assessment by the health department, are recommended to isolate themselves at home with regular health monitoring (up to the 14th day after the last contact with the confirmed case of infection) .The contact persons should keep a diary in which the Body temperature, symptoms and possible other contact persons are noted. The health department reports daily to be informed about the state of health. The contact persons will be informed about the COVID-19 clinical picture and should be registered by name. If symptoms occur during the quarantine at home that indicate a SARS-CoV-2 infection, the contact person will be viewed as a suspected case and a diagnostic clarification will be initiated after consulting the health department.

Category II persons are advised to isolate themselves at home on a voluntary basis; registration by name is optional. Here too, the health department must be informed immediately if symptoms occur. In the case of domestic segregation, inter alia to separate the contact person temporally and spatially from other household members and to pay attention to hygiene (hand washing, coughing labels). The management of people in Category III serves to avoid nosocomial transmission of the virus. It is important that medical personnel are protected from infections by using personal protective equipment (PPE), but that training and organizational measures should also prevent viruses from being transmitted in the work area. If possible, the medical staff who care for COVID-19 patients should not be tasked with caring for other patients. The medical staff should be sensitized and monitor themselves for symptoms, the results as well as the PPE used should be noted in a diary.

In the case of contact persons I, domestic isolation is refrained from if they themselves have been through the infection in the last three months as a laboratory-confirmed case.

Play media file

New types of vaccines are used against the coronavirus. This video shows how vaccination with an mRNA vaccine works.

Play media file

New types of vaccines are used against the coronavirus. This video shows how vaccination with a vector vaccine works.

Vaccinations

The Standing Vaccination Commission ( STIKO ) of the Robert Koch Institute recommends vaccination against COVID-19 for people aged 18 and over in their vaccination calendar . The goals of vaccination against COVID-19 are diverse: protecting every individual from the disease, protecting those particularly at risk, stopping a pandemic wave, maintaining individual freedom, protecting the economy, protecting the least endangered from vaccine side effects, global justice. These partly divergent goals imply different possible strategies regarding vaccine distribution, vaccination prioritization, interval between first and second vaccination, number of booster vaccinations and dose selection.

Vaccines and vaccine candidates

Future vaccination center in the RuhrCongress Bochum

The SARS-CoV-2 vaccine article lists the previously → approved COVID-19 vaccines , the → vaccine candidates in clinical trials and the → vaccine candidates in preclinical trials in tabular form . Information on vaccine development , drug safety , vaccine effectiveness and drug approval can also be found in the article .

According to the World Health Organization (as of June 1, 2021), 102 vaccines are in clinical trials worldwide . Another 185 are in preclinical development. The approved vaccines are now used worldwide (see progress in vaccination campaigns ).

The scientifically published data on the vaccines tozinameran , AZD1222 , mRNA-1273 and Ad26.COV2.S show that the number of serious diseases is significantly reduced regardless of the vaccine. Since the introduction of the virus variant Delta, however , the vaccines no longer protect against virus transmission as well as before. According to the WHO , vaccinated people are as contagious as those who are not vaccinated.

Booster vaccination and additional vaccine doses for those with a primary vaccination

A worldwide corona wave, caused by the highly transmissible Delta variant , led to discussions in mid-September 2021 about the need and the optimal time to administer another dose of a COVID-19 vaccine to people who are already completely resistant to severe courses of COVID- 19 disease are basic immunized. A collective of authors pointed out in the medical journal The Lancet in mid-September 2021 that any decision in this regard should be evidence-based and take into account the benefits and risks for individuals and society.

It is to distinguish between a dose for booster vaccination ( English booster dose ) for those sufficient to primary immunization against COVID-19 have raised, and an additional dose of vaccine ( English extra-dose ) of a SARS-CoV-2 vaccine for people with weakened Immune system that did not respond adequately to the basic series of vaccinations.

Booster dose to restore vaccination protection

A booster dose should be given to people who have been fully vaccinated against COVID-19 to restore protection against the disease after the protection achieved by the series of basic vaccinations has waned. The benefits and risks of a possible booster dose need to be clearly defined and compared beforehand.

Comirnaty (BioNTech / Pfizer)

The Scientific Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has concluded that the COVID-19 vaccine Comirnaty (BioNTech / Pfizer) can be used for booster vaccinations for people aged 18 and over at least 6 months after the second dose of the series of basic courses has been given can be considered. Analysis of the data available to date has shown that in people aged 18 to 55 years, an increase in antibody levels occurs when a booster dose is given approximately six months after the second dose of the vaccine has been administered. National health authorities can now make official recommendations for booster vaccinations with Comirnaty . New data on the efficacy and limited safety of the mRNA vaccine must be taken into account. The information about the booster vaccination with Comirnaty are (in the updated product information of the product characteristics Summary and package insert included).

Spikevax (Moderna)

The European Medicines Agency (EMA) Voices is on 25 October 2021 an already booster reason immunized with the COVID-19 vaccine Spikevax (Moderna) from. In the opinion of the EMA's Committee for Medicinal Products for Human Use (CHMP), a third dose of vaccine can now be considered for people aged 18 and over who have already received a second dose of this mRNA vaccine . The basis for this recommendation form data showing that a third dose Spikevax administered six to eight months after the primary immunization in adults whose antibody - titer can increase significantly. For a booster vaccination with Spikevax , half of the dose used for the first vaccination should be used in accordance with the EMA. Current data suggest that the pattern of expected side effects after the booster vaccinations is similar to that after the second dose. The possible occurrence of inflammatory heart disease or other very rare side effects after booster vaccinations will be carefully monitored. As with all medicines, the EMA will continue to review all data on the safety and effectiveness of Spikevax . At the national level, the responsible health authorities can now officially make recommendations for booster vaccinations with Spikevax . The local epidemiological situation as well as new data on the effectiveness of the vaccine and the limited safety-related data for the booster vaccinations must be taken into account. Refer to the updated product information sheet for information on booster vaccinations with Spikevax .

Ad26.COV2.S (Janssen / Johnson & Johnson)

As of October 15, 2021, no approval has been applied for the administration of booster vaccinations against COVID-19. Approval for the administration of booster vaccinations against COVID-19 has not yet been applied for for the COVID-19 vaccine Ad26.COV2.S (Janssen / Johnson & Johnson). Independently of this, the Standing Vaccination Commission  (STIKO) in Germany has  recommended that a booster dose be given to people who have had a basic vaccination with Ad26.COV2.S (Janssen / Johnson & Johnson). According to the STIKO, people who have already been vaccinated with this vector vaccine should receive a booster dose of an mRNA vaccine ( Spikevax from Moderna or Comirnaty  from Biontech / Pfizer) at the earliest four weeks after the primary vaccination to maintain their immune protection against COVID-19. The recommendation of STIKO based on the fact that relative to the number of administered doses of vaccine in Germany, most vaccine breakthrough disease were observed after COVID-19 vaccines in individuals with the Ad26.COV2.S had been vaccinated (Janssen / Johnson & Johnson). In addition, the effectiveness of this vector vaccine against the Delta variant is lower than that of the other COVID-19 vaccines.

Ad26.COV2.S (Janssen / Johnson & Johnson): The EMA's Human Medicines Committee ( CHMP ) has concluded that a booster dose of Ad26.COV2.S should be considered in people aged 18 and over at least two months after the first dose can be. The recommendation follows data showing that after a booster dose of the COVID-19 vaccine Ad26.COV2.S given at least two months after the first dose in adults, an increase in antibodies to SARS-CoV-2 ( the virus that causes COVID-19). Very rare side effects after a booster vaccination with Ad26.COV2.S are not known. Possible risks of thrombosis in combination with thrombocytopenia (TTS) or other rare side effects after a booster treatment is monitored ( monitoring ). The CHMP also concluded that a booster dose of Ad26.COV2.S could be given after two doses of any of the EU-approved mRNA vaccines, Comirnaty (BioNTech / Pfizer) or Spikevax (Moderna). All data on the safety and effectiveness of Ad26.COV2.S will continue to be checked by the EMA. National health authorities may make official recommendations for the use of booster doses either after a dose of Ad26.COV2 , taking into account the local epidemic , vaccine availability, emerging vaccine efficacy and limited drug safety data for the primer vaccination against COVID-19 . Speak S or after two doses of an mRNA vaccine . Data to support the COVID-19 vaccine refreshment advice from Janssen will be available in the updated product information sheet. However, the US Food and Drug Administration and the US  CDC do not recommend vaccinating adults with the COVID-19 vaccine Ad26.COV2.S (Janssen / Johnson & Johnson). Instead, the mRNA- based COVID-19 vaccines Comirnaty (BioNTech / Pfizer) or Spikevax (Moderna) should be administered. These recommendations are based on the occurrence of thrombosis-with-thrombocytopenia syndrome (TTS) in the USA. After inoculation of Ad26.COV2.S , 54 cases of TTS occurred according to the CDC. All 54 patients were hospitalized, 36 of them were treated in the intensive care unit, nine died. Of 54 patients, 37 were female; the mean age of those with TTS was 44 years. However, the CDC pointed out that vaccination with Ad26.COV2.S is better than no vaccination against COVID-19 at all, especially for people who do not want or cannot have vaccination with mRNA vaccines. The vaccination with Ad26.COV2.S had already been suspended once in the USA in the spring of 2021 after the occurrence of the first cases of TTS after vaccination of this vector vaccine.

Vaxzevria (AstraZeneca / Oxford)

For the COVID-19 vaccine Vaxzevria (AstraZeneca / Oxford), approval for the administration of booster vaccinations against COVID-19 has not yet been applied for in Europe as of October 15, 2021.

Vaccine doses to supplement the primary series

An additional dose of vaccine should be considered for people with a severely weakened immune system as a supplement to the primary series, as these individuals may not achieve adequate protection from the primary series.

Organ transplant recipients are among those with severely compromised immune systems . Studies have shown that an additional dose of the COVID-19 vaccines Comirnaty (BioNTech / Pfizer) or Spikevax (Moderna) increases the ability of these patients to produce antibodies against the SARS-CoV-2 coronavirus . While the ability to produce antibodies has not yet been shown to protect these patients from COVID-19 disease, an extra dose of vaccine is expected to increase protection in at least some. Any data on vaccine efficacy will continue to be monitored by the EMA and the product information (i.e. summary of product characteristics and package insert ) for both vaccines will be updated as recommended on October 4, 2021.

Comirnaty (BioNTech / Pfizer): People who have been vaccinated with a dose of 'Comirnaty' should also receive 'Comirnaty' as the second dose of the primary vaccination series. Giving a third dose of Comirnaty to people with severe immunosuppression can be considered at least 28 days after the second dose of the vaccine. The interchangeability of 'Comirnaty' with other COVID-19 vaccines to complete the primary vaccination series (third dose) has not been established. The EMA's recommendation to consider a third dose of the mRNA vaccine Comirnaty in severely immunocompromised individuals is based on limited serological evidence from a case series in the literature on the clinical treatment of patients with iatrogenic immunosuppression after solid organ transplantation, such as B. kidneys, heart, lungs or liver. The effectiveness and safety of the vaccine has not been evaluated in immunocompromised subjects, including those receiving immunosuppressants.

Spikevax (Moderna): In severely immunocompromised people (12 years and older), a third dose of 'Spikevax' (0.5 ml) can be considered 28 days after the second dose at the earliest as part of the primary vaccination course. The efficacy and safety of the vaccine have not been studied in people who are immunocompromised, including those on immunosuppressant therapy . The EMA's recommendation to consider a third dose in severely immunocompromised individuals is based on limited serological evidence from patients immunocompromised after a single organ transplant.

See also:

• in the article "vaccination" → section: " refreshment "
• in the article "SARS-CoV-2 vaccine" → section: " Booster vaccinations and additional vaccine doses for those with a primary vaccination "
• in the article "COVID-19 vaccination in Germany" → Section: "Booster vaccination "

General vaccination prophylaxis

The Berlin Senate Health Administration recommended the end of February 2020 all people over 60 and the chronically ill, their vaccination status to check and possibly vaccination against pneumococcal and whooping cough perform (pertussis) or to brush up. Since people over 60 years of age and the chronically ill are particularly at risk from multiple infections, they should be protected as a precaution.

Due to the protective measures against a SARS-CoV-2 infection, the flu wave 2020/21 failed worldwide; The spread of influenza viruses was also successfully contained as a side effect. In the coming winter of 2021/22, however, our immune system could be less well prepared for the influenza viruses that will then be circulating. People with an increased health risk, including people over the age of 60, pregnant women and the chronically ill of all age groups, but also medical and nursing staff who are at risk of occupational infection, should therefore get a preventive flu vaccination in October, November or the first half of December.

The effectiveness of a flu vaccination may be less in the elderly. In order to better protect this group of people from flu and related complications, the Standing Vaccination Commission (STIKO) at the RKI recommends a high-dose flu vaccine specially developed for this age group for people aged 60 and over . High-dose influenza vaccines have slightly but significantly better efficacy in seniors than inactivated, quadrivalent standard influenza vaccines . In addition, vaccination against flu and protection against COVID-19 is possible at the same time.

Actions in the event of death

According to the recommendations of the RKI, any physical contact or the release of liquids and aerosols must be avoided when handling people who have died of COVID-19. A necessary inquest must be carried out under protection level 3 regulations . COVID-19 must be specified by name on the death certificate and coffins must be marked.

Notification requirement, ICD-10 classification, occupational disease

In Germany, suspected disease, the disease and death in relation to the coronavirus disease-2019 are notifiable since May 23, 2020 in accordance with Section 6 (1) No. 1 lit. t of the Infection Protection Act (IfSG) . The obligation to notify was introduced by ordinance on February 1, 2020 . Since the legal regulation by the " Second Act for the Protection of the Population in an Epidemic Situation of National Scope ", the state of treatment for the disease (including recovery) and the serostatus must also be specified by doctors and health authorities ( Section 9 Paragraph 1 No. 1 lit . n, § 11 Paragraph 1 No. 1 lit.d and j IfSG). The clinical-epidemiological criteria for the suspicion are determined and published by the Robert Koch Institute as in the previous ordinance (as case definitions according to Section 11 (2) IfSG).

In addition, laboratories in Germany are obliged to report the SARS-CoV-2 virus in relation to humans. Since July 2, 2020, there has been an obligation to report if pets have tested positive.

In Austria, there is also an obligation to notify under the Epidemic Act of 1950 together with an ordinance. The duty to report exists for suspected illnesses and deaths due to this virus. In addition, the segregation ordinance was expanded to include the new corona virus.

There is also a reporting requirement in Switzerland . This follows from the Swiss Epidemics Act in conjunction with the Epidemics Ordinance and the Ordinance of the Federal Department of Home Affairs (FDHA) on the reporting of observations of communicable diseases in humans. According to Annex 1 of the EDI Ordinance, doctors must report a clinical suspicion and the initiation of a pathogen-specific laboratory diagnosis and the necessary epidemiological connection. According to Annex 3 of the EDI Ordinance, laboratories must report positive and negative findings (i.e. evidence). The Federal Office of Public Health has published criteria for suspicion, sampling and reporting.

Classification according to ICD-10-GM
U08.9	Personal history of COVID-19, unspecified
U09.9!	Post-COVID-19 condition, unspecified
U10.9	Multisystemic inflammatory syndrome in connection with COVID-19, unspecified
U99.0!	Special procedures for testing for SARS-CoV-2
ICD-10 online (GM version 2021)

On February 17, 2020, the World Health Organization (WHO) included the disease in the International Classification of Diseases (ICD) in the current, internationally valid edition ICD-10-WHO (Version 2019) under code number »U07.1«. For the ICD-10-GM (German Modification) applicable in Germany, the exclamation mark key number »U07.1!« Was assigned as a secondary code and the disease was designated as COVID-19 (Coronavirus-Disease-2019) . A corresponding addition was made for the cause of death coding in the ICD-10-GM. On March 23, 2020, the WHO made an adjustment aimed at being able to code suspected cases as well. Correspondingly, the key number »U07.1« is used to encode COVID-19 diseases confirmed by laboratory diagnostics , while the »key number U07.2« is intended for cases that have been confirmed clinically and epidemiologically, but not by laboratory diagnostics. For the ICD-10-GM , the coding is analogous in the form of the two secondary codes »U07.1!« With the designation: COVID-19, virus detected and »U07.2!« With the designation: COVID-19, virus not proven . The second only applies if there was previously a suspicion of COVID-19. If there was no suspicion of an illness, a test for SARS-CoV-2 was carried out and this test turns out negative, then “U99.0!” For special procedures for testing for SARS-CoV-2 must be coded together with “Z11 «For special methods of testing for infectious and parasitic diseases .

Classification according to ICD-10-GM
U11.9	Need for vaccination against COVID-19, unspecified
U12.9!	Unwanted side effects when using COVID-19 vaccines, unspecified
ICD-10 online (GM version 2021)

In November 2020, the BfArM (formerly DIMDI) published new codes in its newsletter, which the WHO added to the ICD-10 on November 11, 2020. These codes can also be used in Switzerland from 2021.

In March 2021, the BfArM will publish new codes related to the Covid-19 vaccination. In Germany, these codes are to be used from March 10, 2021.

According to German law , COVID-19 can be recognized as an occupational disease if the sick person worked in the health service, welfare work or in a laboratory or was particularly exposed to the risk of infection to a similar extent through another activity.

COVID-19, animals and pets

→ Main article : Section “Pets as possible hosts” in the article SARS-CoV-2

While individual viruses within the coronavirus family Coronaviridae , such as CCoV and FCoV , also cause diseases in pets, in the first few months of the coronavirus pandemic, no case was initially known in which a pet fell ill with SARS-CoV-2. Although the virus was found in smears taken from the nose and snout in dogs, it did not cause any disease. After initially only a single case of a cat with symptoms of the disease in Belgium became known, a more extensive serological study showed that antibodies and thus a previous infection were detectable in almost 15% of the animals examined.

According to the WHO, there is still no evidence that pets can spread the virus as a carrier. Experiments with ferrets in South Korea showed, however, that non-infected animals can be infected through prolonged direct contact with infected animals (keeping them in the same cage). Sick ferrets develop a course of several days with symptoms such as a slight fever, cough and reduced physical activity. Another study at the beginning of April also demonstrated this susceptibility in cats. According to the authors, aerosol transmission is an option. The viral load in the nasopharynx was highest in both animal species. The lungs of ferrets and other organs were not affected, but cats were. Dogs showed a low risk of infection; in pigs, chickens and ducks, both the PCR smear and the ELISA antibody test were negative after 14 days.

In January 2021, gorillas tested positive for SARS-CoV-2 at the San Diego Zoo; the first great apes to be found to have COVID-19.

Several thousand American mink died in the US state of Utah , probably infected by animal keepers.

There are numerous mink farms in the Netherlands. Dutch authorities reported at the end of May 2020 that two workers were “very likely” to have been infected with COVID-19 through contact with mink. The WHO announced that it could be the "first known cases" of the virus being transmitted from animals to humans (details and evidence → COVID-19 pandemic in the Kingdom of the Netherlands # economy and business ).

In Denmark , the Fødevarestyrelsen (Food Authority ) is investigating 120 mink farms. In the municipality of Hjørring , she independently found three farms with SARS-CoV-2-infected mink; all of the minks on these farms were killed.

In June, the same mutation of a SARS-CoV-2 virus was found in mink, mink breeders, the dog of a mink breeder and 41 residents of a nursing home. Three of the residents died. SARS-CoV-2 was also found in students at three different schools.

In November, the Danish government decided a precautionary culling of the entire national Nerzbestands. On November 5, 2020, the Danish government imposed a “hard regional lockdown” on parts of northern Denmark in the general public due to the increasing spread of SARS-CoV-2 viruses mutated in mink (especially the more antibody-resistant “ Cluster 5 ” variant).

An experimental vaccine against COVID-19 is being tested on the endangered ( Endangered , IUCN 3.1) black-footed tissues. Finland is developing a vaccine for raccoon dogs and American mink to avoid mass culls on fur farms. Russia is also developing a vaccine for mink, cats and rodents . According to planning, this should be available at the end of January 2021.

See also

Portal: COVID-19  - Overview of Wikipedia content on the topic of COVID-19

• List of deaths from the COVID-19 pandemic

literature

German speaking

• Kristin Tolksdorf, Silke Buda, Ekkehard Schuler, Lothar H. Wieler , Walter Haas : A higher mortality rate and long ventilation times differentiate COVID-19 from severe respiratory infections in flu waves . In: Epidemiological Bulletin . No. 41, 2020, pp. 3–10, online August 28, 2020, doi: 10.25646 / 7111 .
• Julia Schilling, Michaela Diercke, Doris Altmann, Walter Haas, Silke Buda: Preliminary assessment of the disease severity of COVID-19 in Germany based on reported cases in accordance with the Infection Protection Act . In: Epidemiological Bulletin . No. 17, 2020, pp. 3–9, online April 15, 2020, doi: 10.25646 / 6670.2 .
• Ralf Stahlmann , Hartmut Lode : Therapy of COVID-19 - first clinical studies with various active ingredients . In: Deutsches Ärzteblatt . Volume 117, No. 13, March 27, 2020, pp. 213-219, doi: 10.3238 / arztebl.2020.0213 ( aerzteblatt.de ).
• Kristin Tolksdorf, Silke Buda, Ekkehard Schuler, Lothar H. Wieler, Walter Haas: Severity assessment of COVID-19 with comparative data on pneumonia from hospital sentinel for severe acute respiratory diseases at the RKI (ICOSARI) . In: Epidemiological Bulletin . No. 14, 2020, pp. 3–9, online March 27, 2020, doi: 10.25646 / 6601 .

English speaking

• Christian Drosten / Thijs Kuiken et al .: Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome, The Lancet, Volume 362, 2003, pp. 263-270.
• Tingbo Liang (Ed.): Handbook of COVID-19 Prevention and Treatment. First Affiliated Hospital, Zhejiang University School of Medicine, 2020 online publication, available as a PDF from the Alibaba.com cloud service , accessed April 8, 2020.
• Kai Kupferschmidt : Evolving threat - New variants have changed the face of the pandemic. What will the virus do next? In: science.org (ed.): Science . tape 373 , no. 6557 , August 19, 2021, p. 844-849 , PMID 34413220 (English, science.org [accessed August 30, 2021]).

Web links

Commons : COVID-19  - Collection of Pictures, Videos and Audio Files

Wiktionary: Directory of words related to COVID-19 / Corona  - explanations of meanings, word origins , synonyms, translations

Profile, FAQs, news

• Profile on COVID-19 Robert Koch Institute (Germany)
• Novel coronavirus (COVID-19) Federal Ministry of Social Affairs, Health, Care and Consumer Protection (Austria) (with link to the official dashboard on COVID-19 )
• Coronavirus: illness, symptoms, treatment Federal Office of Public Health (Switzerland)
• Questions and answers on COVID-19 European Center for Disease Prevention and Control (English)
• Q&A: Coronavirus disease (COVID-19) World Health Organization (English)
• CORD-19 - COVID-19 Open Research Dataset thousands of scientific publications online
• Articles on the topic of Corona Website of the WDR program Quarks
• S1 guideline for preventing infection by wearing masks from the Society for Virology (GfV). In: AWMF online (as of 11/2020)
• COSMO - COVID-19 Snapshot Monitoring Results from the repeated cross-sectional monitoring of knowledge, risk perception, protective behavior and trust during the current COVID-19 outbreak; a joint project of the University of Erfurt , Robert Koch Institute , Federal Center for Health Education , Leibniz Institute for Psychology , Science Media Center , Bernhard Nocht Institute for Tropical Medicine and Yale Institute for Global Health.

Documentation

• Corona - end in sight? "What science knows about SARS-CoV-2". In: ZDF - planet e. , Video documentation, 28 minutes. Published by ZDF , January 17, 2021, accessed on February 15, 2021 (in the ZDF media library → available until January 13, 2023). 
• How Corona settled in Europe (interactive) Time Online , April 8, 2021

Effects on the human body

• Covid-19: Effects on the whole body NDR video (2:48 min.), June 4, 2020
• Sars-CoV-2: How the virus devastates the body Spektrum.de , June 26, 2020
• Coronavirus - How the body works against it - Antibodies are not the only weapon against Corona AFP / t-online , December 23, 2021

COVID-19 therapy

• Recommendations for inpatient treatment of patients with COVID-19 S3 guideline , AWMF register no. 113/001, as of October 5, 2021
• Treatments and vaccines for COVID-19 Overview of the European Medicines Agency (English)
• IDSA Guidelines on the Treatment and Management of Patients with COVID-19 Guidelines of the Infectious Diseases Society of America (English), as of December 24, 2021
• COVID-19 Treatment and Vaccine Tracker Overview of ongoing projects on the Milken Institute websitein California

Individual evidence

1. ↑ § 6 Paragraph 1 No. 1 lit. t of the Infection Protection Act (Germany).
2. ↑ ^{a b} ICD-10 (WHO and GM): U07.2 codes suspicion of COVID-19. In: dimdi.de. German Institute for Medical Documentation and Information, March 23, 2020, accessed on August 14, 2020 . 
3. ↑ terminology collection INFEC20 - Terminology of communicable diseases, keyword COVID-19 , ed. from Switzerland. Federal Chancellery.
4. ↑ Switzerland: Alternative terms: Covid-19 disease , Covid-19 disease . French: maladie à coronavirus 2019 ; Italian: malattia da coronavirus 2019 ; Romansh: malsogna da coronavirus 2019 .
5. ↑ RKI press office : Epidemiological profile on SARS-CoV-2 and COVID-19. (Section 7: Diagnostics). In: RKI website on SARS-CoV-2. Robert Koch Institute (RKI), January 25, 2021, accessed on January 27, 2021 (as of January 25, 2021). 
6. ↑ WHO : WHO Coronavirus Disease (COVID-19) Dashboard. On: covid19.who.int , as of December 28, 2021.
7. ↑ SARS-CoV-2 profile on Coronavirus-Disease-2019 (COVID-19) On: rki.de , as of September 18, 2020.
8. ↑ ^{a b} Sars-CoV-2 virus: Air humidity plays an important role in aerosols. In: Spiegel Online. August 18, 2020, accessed on August 18, 2020 . 
9. ↑ Christian Honey: Coronavirus: What to do against aerosol transmission? In: Spektrum.de. July 10, 2020, accessed on August 14, 2020 . 
10. ↑ Why do some COVID-19 patients infect many others, whereas most don't spread the virus at all? Science , May 19, 2020, accessed August 14, 2020 . 
11. ↑ ^{a b c d e f g h i j} Epidemiological profile on SARS-CoV-2 and COVID-19. Robert Koch Institute , February 9, 2021, accessed on February 21, 2021 .  
12. ↑ D. Baud, X. Qi, K. Nielsen-Saines et al .: Real estimates of mortality following COVID-19 infection . In: The Lancet . tape 20 , March 12, 2020, p. 773 , doi : 10.1016 / S1473-3099 (20) 30234-6 (English, thelancet.com [PDF; 360 kB ; accessed on August 14, 2020]).
13. ^ "Q&A on coronaviruses (COVID-19)". Symptoms of COVID-19. World Health Organization (WHO), April 17, 2020, accessed on August 14, 2020 . 
14. ↑ ^{a b} Zunyou Wu, Jennifer M. McGoogan, CCDC: Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China . In: Journal of the American Medical Association . February 24, 2020, doi : 10.1001 / jama.2020.2648 (English).
15. ↑ Fu-Sheng Wang: Liver injury in COVID-19: management and challenges . In: Lancet Gastroenterology & Hepatology . March 4, 2020, doi : 10.1016 / S2468-1253 (20) 30057-1 .
16. ↑ Yeshun Wu et al .: Nervous system involvement after infection with COVID-19 and other coronaviruses . In: Brain, Behavior and Immunity . Elsevier , March 30, 2020, doi : 10.1016 / j.bbi.2020.03.031 .
17. ↑ ^{a b} Bo Diao et al .: Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection . Open access. In: Nature Communications . tape 12 , May 4, 2021, 2506, doi : 10.1038 / s41467-021-22781-1 (English, nature.com [PDF; 16.2 MB ; accessed on September 12, 2021]): “can directly infect human kidney, thus leading to acute kidney injury (AKI). [...] retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. " , preprint was doi : 10.1101 / 2020.03.04.20031120
18. ↑ Frank Ruschitzka et al .: Endothelial cell infection and endotheliitis in COVID-19 . In: The Lancet . April 17, 2020, doi : 10.1016 / S0140-6736 (20) 30937-5 .
19. ↑ RM Inciardi, L. Lupi, G. Zaccone, et al .: Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19) . In: JAMA Cardiol . March 27, 2020, doi : 10.1001 / jamacardio.2020.1096 .
20. ↑ Valentina O. Puntmann, M. Ludovica Carerj, Imke Wieters, Masia Fahim, Christophe Arendt: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) . In: JAMA Cardiology . July 27, 2020, doi : 10.1001 / jamacardio.2020.3557 ( online [accessed on August 14, 2020]).
21. ↑ How long does COVID-19 last? Retrieved December 24, 2020 . 
22. ↑ Gareth Iacobucci: Long covid: Damage to multiple organs presents in young, low-risk patients . In: BMJ . tape 371 , November 17, 2020, ISSN  1756-1833 , doi : 10.1136 / bmj.m4470 ( bmj.com [accessed December 24, 2020]).
23. ↑ Elisabeth Mahase: Long covid could be four different syndromes, review suggests . In: BMJ . tape 371 , October 14, 2020, ISSN  1756-1833 , doi : 10.1136 / bmj.m3981 , PMID 33055076 ( bmj.com [accessed December 24, 2020]).
24. ↑ Fernando P. Polack et al .: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine . In: New England Journal of Medicine . December 10, 2020, doi : 10.1056 / NEJMoa2034577 , PMID 33301246 , PMC 7745181 (free full text) - ( nejm.org [accessed December 24, 2020]).
25. ↑ Evan J. et al .: Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults . In: The New England Journal of Medicine . September 29, 2020, ISSN  0028-4793 , doi : 10.1056 / NEJMoa2028436 , PMID 32991794 , PMC 7556339 (free full text).
26. ↑ Evan J. et al .: Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults . In: New England Journal of Medicine . September 29, 2020, doi : 10.1056 / NEJMoa2028436 , PMID 32991794 , PMC 7556339 (free full text) - ( nejm.org [accessed December 24, 2020]).
27. ↑ ^{a b c d} Akbarshakh Akhmerov, Eduardo Marban: COVID-19 and the Heart. Circulation Research, April 7, 2020, doi: 10.1161 / CIRCRESAHA.120.317055
28. ↑ ^{a b} P. Zhang, J. Li, H. Liu et al .: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study . In: Bone Research - Nature . tape 8 , no. 8 , 2020, doi : 10.1038 / s41413-020-0084-5 .
29. ↑ ^{a b} Chia-Husn Huang, Yuan Nian Hsu: First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan . In: Journal of the Formosan Medical Association . 3rd Edition. tape 119 , March 2020, p. 747-751 , doi : 10.1016 / j.jfma.2020.02.007 .
30. ↑ ^{a b} Jing Gao et al .: Sars-Cov-2: Underestimated damage to nervous system . In: Travel Medicine and Infectious Disease . March 24, 2020, doi : 10.1016 / j.tmaid.2020.101642 .
31. ↑ Michael A. Johansson, Daniela Saderi: Open peer-review platform for COVID-19 preprints . In: Nature . March 3, 2020, doi : 10.1038 / d41586-020-00613-4 .
32. ↑ Jon Cohen: Science's Breakthrough of the Year 2020: shots of hope in a pandemic-ravaged world. In: sciencemag.org. Science, December 17, 2020, accessed December 18, 2020 . 
33. ↑ Na Zhu, Dingyu Zhang, Wenling Wang et al .: A Novel Coronavirus from Patients with Pneumonia in China . In: The New England Journal of Medicine . 2019, doi : 10.1056 / NEJMoa2001017 (English).
34. ↑ ^{a b} Jasper Fuk-Woo Chan, Shuofeng Yuan, Kin-Hang Kok et al .: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster . In: The Lancet . January 24, 2020, doi : 10.1016 / S0140-6736 (20) 30154-9 (English).
35. ↑ Michelle L. Holshue, Chas DeBolt et al. for the Washington State 2019-nCoV Case Investigation Team: First Case of 2019 Novel Coronavirus in the United States . In: The New England Journal of Medicine . January 31, 2020, doi : 10.1056 / NEJMoa2001191 (English).
36. ↑ Dongyu Guo: Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection . In: Journal of Medical Virology . February 18, 2020, doi : 10.1002 / jmv.25725 .
37. ↑ Nicky Phillips, Smriti Mallapaty, David Cyranoski: How quickly does the Wuhan virus spread? In: Nature . January 21, 2020, doi : 10.1038 / d41586-020-00146-w (English).
38. ↑ ^{a b} Zhangkai J. Cheng, Jing Shan: 2019 Novel coronavirus: where we are and what we know . In: Infection . February 18, 2020, doi : 10.1007 / s15010-020-01401-y (English).
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280. ↑ BZgA - Infektionsschutz.de: Suspected infection and test .
281. ↑ Federal Ministry of Health (Germany) (Ed.): What should you do if you suspect that you have been infected with the novel coronavirus? , May 5, 2020, accessed October 15, 2020.
282. ↑ Ippen Digital GmbH & Co. KG (Ed.): Do not see a doctor if you suspect Corona: How to behave properly. Website of the Westfälischer Anzeiger , November 30, 2020, accessed on April 26, 2021.
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284. ↑ Federal Ministry of Health (Germany) (Ed.): Your questions - our answers. "If you are sick, go to the doctor or to the hospital". May 25, 2020 ( Memento of October 23, 2020 in the Internet Archive )
285. ↑ Hygiene when coughing and sneezing. (No longer available online.) Federal Center for Health Education , archived from the original on March 13, 2020 ; accessed on March 15, 2020 . 
286. ^ Christian Drosten. Interview: Florian Schumann and Jakob Simmank: It's in our own hands. In: zeit.de. October 6, 2020, accessed October 7, 2020 . 
287. ↑ 8 simple tips for everyday life in the corona pandemic. (PDF) In: rki.de. RKI, March 31, 2020, accessed on March 31, 2021 . 
288. ↑ Derek K. Chu, Elie A. Akl et al .: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. In: The Lancet. June 1, 2020, doi: 10.1016 / S0140-6736 (20) 31142-9 .
289. ↑ ^{a b} Notes on cleaning and disinfecting surfaces outside of healthcare facilities in connection with the COVID-19 pandemic. Robert Koch Institute , July 3, 2020, accessed on August 15, 2020 . 
290. ↑ BfR Bund: Can the new type of coronavirus be transmitted via food and objects? BfR , questions and answers , as of June 29, 2020, (also as PDF), accessed on August 6, 2020.
291. ^ Marianne van der Sande, Peter Teunis, Rob Sabel: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population. In: PLOS ONE , July 9, 2008, doi: 10.1371 / journal.pone.0002618 .
292. ↑ Chi Chiu Leung: Mass masking in the COVID-19 epidemic: people need guidance. In: Lancet ,. March 3, 2020, doi: 10.1016 / S0140-6736 (20) 30520-1 .
293. ↑ JT Brooks, JC Butler, RR Redfield: Universal Masking to Prevent SARS-CoV-2 Transmission — The Time Is Now. In: Journal of the American Medical Association . July 14, 2020. doi: 10.1001 / jama.2020.13107 .
294. ↑ CDC: CDC calls on Americans to wear masks to prevent COVID-19 spread CDC, as of July 14, 2020, accessed on August 6, 2020.
295. ↑ CDC: Coronavirus Disease 2019 (COVID-19) - Prevention & Treatment. April 3, 2020, Retrieved April 3, 2020 (American English). 
296. ↑ Shuo Feng, Chen Shen, Nan Xia, Wei Song, Mengzhen Fan: Rational use of face masks in the COVID-19 pandemic. In: The Lancet . Volume 8, No. 5, May 1, 2020, pp. 434-436, doi: 10.1016 / S2213-2600 (20) 30134-X , PMID 32203710 .
297. ↑ Yafang Cheng et al .: Face masks effectively limit the probability of SARS-CoV-2 transmission. In: Science. Volume 372, No. 6549, 2021, pp. 1439-1443, doi: 10.1126 / science.abg6296 .
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298. ↑ Mingming Liang, Liang Gao, Ce Cheng, Qin Zhou, John Patrick Uy, Kurt Heiner, Chenyu Sun: Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis. In: medRxiv , doi: 10.1101 / 2020.04.03.20051649 .
299. ↑ German Statutory Accident Insurance e. V. (DGUV): FAQ Coronavirus Disease 2019 (COVID-19). Retrieved April 26, 2020 . 
300. ↑ Frankfurter Rundschau: Protection against the corona virus: What face masks and respiratory masks really do. Retrieved April 28, 2020 . 
301. ↑ Federal Institute for Drugs and Medical Devices (BfArM): Information from the BfArM on the use of self-made masks (so-called "community masks"), medical face masks and filtering half masks (FFP1, FFP2 and FFP3) in connection with the coronavirus (SARS- CoV-2 / Covid-19) ( Memento from April 16, 2020 in the Internet Archive ). On: bfarm.de ; As of June 26, 2020, accessed on August 6, 2020.
302. ↑ Prevention of infection by wearing masks. German Society for Hygiene and Microbiology and Society for Virology, November 4, 2020, accessed on May 7, 2021 . 
303. ↑ German Society for Hospital Hygiene (PDF; 308 kB).
304. ↑ Patrick Hunziker: Minimizing exposure to respiratory droplets, 'jet riders' and aerosols in air-conditioned hospital rooms by a 'Shield-and-Sink' strategy . In: BMJ Open . tape 11 , no. 10 , October 1, 2021, ISSN  2044-6055 , p. e047772 , doi : 10.1136 / bmjopen-2020-047772 ( bmj.com [accessed October 13, 2021]).
305. ↑ Patrick Hunziker: Minimizing exposure to respiratory droplets, 'jet riders' and aerosols in air-conditioned hospital rooms by a 'Shield-and-Sink' strategy . In: medRxiv . December 16, 2020, doi : 10.1101 / 2020.12.08.20233056 ( medrxiv.org [accessed December 24, 2020]).
306. ↑ Waste separation more important than ever in times of the coronavirus pandemic - BMU press release. Retrieved April 30, 2020 . 
307. ^ Waste management in the context of the coronavirus crisis. (PDF) European Commission, April 14, 2020, accessed April 30, 2020 . 
308. ↑ George Griffin et al. Vitamin D and COVID-19: evidence and recommendations for supplementation. In: Royal Society Open Science. December 2020, Volume 7, No. 1, Article: 201912, doi: 10.1098 / rsos.201912 .
309. ↑ Marcos Pereira et al. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. In: Critical Reviews in Food Science and Nutrition. November 2020, Volume 4, pp. 1-9, doi: 10.1080 / 10408398.2020.1841090 .
310. ^ B. William B. Grant et al .: Evidence Regarding itamin D and Risk of COVID-19 and Its Severity. In: Nutrients. 2020, Volume 12, No. 11, P. 3361, doi: 10.3390 / nu12113361 .
311. ↑ Debate about vitamin D: But no U-turn by the BfR. In: tagesschau.de. May 17, 2020, accessed May 19, 2021 . 
312. ↑ ^{a b c d e} Hygiene measures in the treatment and care of COVID-19 patients. In: Website of the Robert Koch Institute . March 27, 2020, accessed March 28, 2020 .  
313. ↑ Can FFP masks without CE marking also be used and placed on the market? On: baua.de , as of April 6, 2020 ( Memento from April 11, 2020 in the Internet Archive ) accessed on April 13, 2020.
314. ↑ List of the disinfectants and methods tested and recognized by the Robert Koch Institute. In: Website of the Robert Koch Institute . March 12, 2020, accessed March 28, 2020 .  
315. ↑ Emmie de Wit, Vincent J. Munster et al .: Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. In: NEJM , April 16, 2020, doi: 10.1056 / NEJMc2004973 .
316. ↑ Classification of the incidents in China by Prof. Christoph Benz . Retrieved March 29, 2020.
317. ↑ Do I have to be treated by the dentist in times of corona? br.de, April 1, 2020, accessed on August 6, 2020 . 
318. ↑ All dental treatments are possible again. In: dentalmagazin.de. May 15, 2020, accessed August 6, 2020 . 
319. ↑ Sars-CoV-2 / COVID 19th German Dental Association , July 27, 2020, accessed on August 6, 2020 . 
320. ↑ RKI - Coronavirus SARS-CoV-2 - Recommendations of the RKI on hygiene measures in the context of the treatment and care of patients with an infection by SARS-CoV-2. Retrieved April 30, 2020 . 
321. ↑ Dispose of waste infected with Corona. In: Waste Manager Medicine. Retrieved April 30, 2020 . 
322. ↑ ^{a b} RKI (Ed.): National Pandemic Plan Part I - Structures and Measures . 2017 ( rki.de ).
323. ↑ RKI (Ed.): Supplement to the National Pandemic Plan - COVID-19 - novel coronavirus disease . March 4, 2020 ( rki.de [PDF]).
324. ↑ ^{a b c} ECDC (Ed.): Guidelines for the implementation of non-pharmaceutical interventions against COVID-19 . September 25, 2020 ( europa.eu ).
325. ↑ Jacob Burns et al .: Travel-Related Control Measures to Contain the COVID-19 Pandemic: A Rapid Review . In: Cochrane Database of Systematic Reviews . September 16, 2020, doi : 10.1002 / 14651858.CD013717 .
326. ↑ Meera Viswanathan et al .: Universal screening for SARS-CoV-2 infection: a rapid review . In: Cochrane Database of Systematic Reviews . September 15, 2020, doi : 10.1002 / 14651858.CD013718 .
327. ↑ Barbara Nussbaumer-Streit et al .: Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review . In: Cochrane Database of Systematic Reviews . September 14, 2020, doi : 10.1002 / 14651858.CD013574.pub2 .
328. ^ ^{A b} Alba Mendez-Brito, Charbel El Bcheraoui, Francisco Pozo-Martin: Systematic review of empirical studies comparing the effectiveness of non-pharmaceutical interventions against COVID-19 . In: Journal of Infection . tape 83 (2021) . Elsevier , June 20, 2021, p. 281, 287–290 , doi : 10.1016 / j.jinf.2021.06.018 (English, journalofinfection.com [PDF; 1.7 MB ; accessed on August 31, 2021]): “Early implementation was associated with a higher effectiveness in reducing COVID-19 cases and deaths, while general stringency of the NPIs was not. Conclusions: In this systematic review, we found that school closing, followed by workplace closing, business and venue closing and public event bans were the most effective NPIs in controlling the spread of COVID-19. […] Two health system measures found to be effective in reducing COVID-19 cases are public information campaigns and mask wearing requirements. [...] In contrast, public transport closure, testing strategies, contact tracing strategies and isolation or quarantine strategies showed no evidence of being effective in the studies assessed. [...] In conclusion, a cautious approach for reopening should be adapted to each context, with specific mitigation measures, stepwise opening and monitoring the effects of reopening for in-school and community transmission. [...] The existence of super spreaders is considered to be a common characteristic of coronaviruses, and it is related with several factors, like prolonged indoor gatherings with poor ventilation. [...] Regarding vaccine rollout, they considered that vaccination was increasingly contributing to the pandemic control, despite its effect having a significantly lower impact than the NPIs by the time of the study. "
329. ↑ ^{a b c d} Follow-up of contact persons for SARS-CoV-2 infections. RKI, as of February 5, 2021, accessed on February 7, 2021.
330. ↑ Follow-up of contact persons in the event of respiratory illnesses caused by the SARS-CoV-2 coronavirus. In: Website of the Robert Koch Institute . October 19, 2020, accessed November 14, 2020 .  
331. ^ Forum on Genetic Research of the Swiss Academy of Sciences: mRNA vaccines against the coronavirus. Accessed August 2021 . 
332. ^ Forum on Genetic Research of the Swiss Academy of Sciences: Vector vaccines against the coronavirus. Accessed August 2021 . 
333. ↑ STIKO recommendation for COVID-19 vaccination. In: Epidemiological Bulletin . Volume 25, 2021, June 24, 2021.
334. ↑ Rapid Rollout of COVID Vaccines for 'Everyone, Everywhere' Critical to Blocking Further Resistant Strains, Secretary-General Tells International Forum - World. Accessed August 17, 2021 . 
335. ↑ WHO SAGE Working Group: WHO SAGE ROADMAP FOR PRIORITIZING USES OF COVID-19 VACCINES IN THE CONTEXT OF LIMITED SUPPLY . Ed .: WHO. November 13, 2020 ( who.int [PDF]).
336. ↑ Siri R. Kadire, Robert M. Wachter, Nicole Lurie: Delayed Second Dose versus Standard Regimen for Covid-19 Vaccination . In: New England Journal of Medicine . tape 384 , no. 9 , March 4, 2021, ISSN  0028-4793 , p. e28 , doi : 10.1056 / NEJMclde2101987 ( nejm.org [accessed August 17, 2021]).
337. ↑ Dooling Kathleen: An Additional Dose of mRNA COVID-19 Vaccine Following a Primary Series in Immunocompromised People. Ed .: CDC Advisory Board for Immunization Practices. August 13, 2021 ( cdc.gov [PDF]).
338. ↑ Patrick Hunziker: Personalized-dose Covid-19 vaccination in a wave of virus Variants of Concern: Trading individual efficacy for societal benefit . In: Precision Nanomedicine . tape 4 , no. 3 , July 24, 2021, p. 805-820 , doi : 10.33218 / 001c.26101 ( precisionnanomedicine.com [accessed August 17, 2021]).
339. ↑ Draft landscape of COVID-19 candidate vaccines. (XLS) In: who.int. World Health Organization, June 1, 2021, accessed on June 3, 2021 (English, Excel file 20210106-Novel Coronavirus_Landscape_COVID.xlsx in linked ZIP archive). 
340. ↑ Harder T, Koch J, Vygen-Bonnet S, Scholz S, Pilic A, Reda S, Wichmann O: How well does the COVID-19 vaccination protect against SARS-CoV-2 infections and SARS-CoV-2 transmission? - Systematic review and evidence synthesis Epid Bull 2021; 19: 13-23 | doi: 10.25646 / 8442
341. ↑ WHO : Weekly epidemiological update on COVID-19 - 24 August 2021 (Edition 54). In: Publications / Overview. who.int, August 24, 2021, p. 6 , accessed August 29, 2021 (English). “Table 2: Summary of phenotypic impacts of Variants of Concern, Delta: […] Transmissibility: Increased transmissibility and secondary attack rate, Similar transmissibility between vaccinated and unvaccinated individuals” ( F. Campbell et al., 2021 ; DOI: 10.1101 / 2021.07 .31.21261387 ; DOI: 10.1101 / 2021.07.07.21260122 ; DOI: 10.15585 / mmwr.mm7031e2 ) 
342. ↑ In Europe, from May to the beginning of October 2021, the upper variant B.1.617.2 with the sub-variants AY.4 and AY.9 determined the spread of delta (see: SARS-CoV-2 variant Delta → Other sub-variants AY. * )
343. ↑ R. Krause et al. : Considerations in boosting COVID-19 vaccine immune responses. In: The Lancet . September 13, 2021, accessed on October 26, 2021 (German-language editing supported by  DEEPL translators). 
344. ↑ ^{a b c d} Comirnaty and Spikevax: EMA Recommendations for Additional Doses and Booster Vaccinations. In: EMA website. European Medicines Agency (EMA), October 4, 2021, accessed on October 13, 2021 (translation supported by  DEEPL translators). 
345. ↑ ^{a b c} ECDC and EMA highlight considerations for additional and booster doses of COVID-19 vaccines. In: EMA website. EMA , February 9, 2021, accessed September 24, 2021 (English, translation supported by Google Chrome). 
346. ↑ ^{a b c} Interim Public Health Considerations for Providing Additional COVID-19 Vaccine Doses. In: ECDC website. ECDC , September 2, 2021, accessed on September 24, 2021 (English, editing supported by Google Chrome). 
347. ↑ Comirnaty,, Summary of Product Characteristics , as of October 15, 2021. Retrieved October 28, 2021.
348. ↑ Spikevax : EMA recommendation for booster vaccination. In: European Medicines Agency . October 25, 2010, accessed on October 27, 2021 (German-language editing supported by  DEEPL translators). 
349. ↑ Christina Hohmann-Jeddi: Covid-19 vaccination : EMA advocates refreshment with Spikevax. In: Pharmazeutische Zeitung (PZ). October 26, 2021, accessed on October 27, 2021 ("The European Medicines Agency is in favor of a booster vaccination with the Spikevax® corona vaccine from Moderna. A booster dose could be considered for adults, the authority announced on Monday [October 25, 2021] . “→ Source: ibid). 
350. ↑ Spikevax, Summary of Product Characteristics , as of October 25, 2021. Retrieved October 28, 2021.
351. ^ ^{A b} Theo Dingermann: FDA complains about the Janssen vaccine. (Section: The STIKO has already positioned itself ). In: Pharmaceutical Newspaper . October 15, 2021, accessed on November 11, 2021 ( doi: 10.1101 / 10.10.21264827 2021 ). 
352. ↑ COVID-19 Vaccine Janssen: EMA recommendation on booster dose. In: EMA website. European Medicines Agency (EMA), December 15, 2021, accessed on December 19, 2021 (German-language editing supported by DEEPL translator ). 
353. ↑ Corona vaccination US authorities FDA and CDC advise against Johnson & Johnson vaccines. In: aerztezeitung.de . December 17, 2021, accessed on December 19, 2021 : "The US FDA and CDC advise better vaccinating adults with the Comirnaty® or Spikevax® vaccines instead of the COVID-19 vaccine from Johnson & Johnson." 
354. ↑ Comirnaty and Spikevax: EMA Recommendations for Additional Doses and Booster Vaccinations. In: EMA website. European Medicines Agency (EMA), October 4, 2021, accessed on October 13, 2021 (processing supported by  DEEPL translator). 
355. ↑ Comirnaty - Summary of Product Characteristics. (PDF) In: Comirnaty: EPAR - Product information (updated). European Medicines Agency (EMA), p. 2 , accessed on October 17, 2021 (First published: 12/01/2021 / Last updated: 15/10/2021). 
356. ↑ Comirnaty - Summary of Product Characteristics. (PDF) In: Comirnaty: EPAR - Product information (updated). European Medicines Agency (EMA), p. 5 , accessed on October 17, 2021 (First published: 12/01/2021 / Last updated: 15/10/2021). 
357. ↑ Comirnaty - Summary of Product Characteristics. (PDF) In: Spikevax: EPAR - Product information (updated). European Medicines Agency (EMA), p. 2 , accessed on October 17, 2021 (First published: 20/01/2021 / Last updated: 12/10/2021). 
358. ↑ Comirnaty - Summary of the 8 characteristics of the drug. (PDF) In: Spikevax: EPAR - Product information (updated). European Medicines Agency (EMA), p. 4 , accessed on October 17, 2021 (First published: 20/01/2021 / Last updated: 12/10/2021). 
359. ↑ Health Senator welcomes expansion of the risk area through the Robert Koch Institute. In: berlin.de. February 26, 2020, accessed February 29, 2020 . 
360. ↑ Coronavirus: When does a disaster apply - and what follows? In: rbb24.de. February 26, 2020, accessed February 29, 2020 . 
361. ↑ ^{a b c} Prevent the flu now - with the flu vaccination! (As of October 10, 2021). In: PEU website. Paul Ehrlich Institute (PEI), October 6, 2021, accessed on October 11, 2021 ("In autumn 2021, the flu vaccination is particularly important against the background of the corona pandemic. The Federal Ministry of Health (BMG), the Federal Center for Health Enlightenment (BZgA), the Robert Koch Institute (RKI) and the Paul Ehrlich Institute (PEI) therefore particularly appeal to people with an increased risk of severe flu to get vaccinated now. ”→ Source: ibid ). 
362. ↑ Quadruple Vaccines
363. ↑ Answers to frequently asked questions about vaccination against influenza / high-dose vaccine. (As of September 7, 2021). In: RKI website. Robert Koch Institute (RKI), September 7, 2021, accessed on October 11, 2021 . 
364. ↑ Recommendations for dealing with SARS-CoV-2 infected deceased. In: Robert Koch Institute. April 7, 2020, accessed April 22, 2020 . 
365. ↑ Protection package for more corona tests and care premiums decided. German Bundestag, May 14, 2020, accessed on May 14, 2020 . 
366. ↑ ^{a b} Bill of the parliamentary groups of the CDU / CSU and SPD. (PDF) Draft of a second law for the protection of the population in the event of an epidemic situation of national concern. In: Bundestag printed matter 19/18967. May 5, 2020, pp. 2, 54 f. , Accessed on May 14, 2020 . 
367. ↑ Recommendations of the Robert Koch Institute for reporting suspected cases of COVID-19. Robert Koch Institute, May 29, 2020, accessed on May 31, 2020 . 
368. ↑ Obligation to report corona infections in pets. Press and Information Office of the Federal Government, July 2, 2020, accessed on November 1, 2020 . 
369. ↑ Epidemic Act 1950. Consolidated Federal Law, Entire Legal Regulation. In: RIS . June 14, 2018, accessed on March 6, 2020 : "Subject to the reporting requirement: [...] (2) The Federal Minister for Health and Women can, [...], make other communicable diseases subject to the reporting requirement or expand existing reporting requirements." 
370. ↑ 15. Ordinance of the Federal Minister for Labor, Social Affairs, Health and Consumer Protection regarding notifiable communicable diseases 2020. In: Federal Law Gazette for the Republic of Austria . January 26, 2020, accessed on March 4, 2020 : "The obligation to notify under the Epidemic Act 1950 is subject to suspected illnesses and deaths from 2019-nCoV ('2019 novel coronavirus')." 
371. ↑ Separation Ordinance. Consolidated federal law: Entire legal regulation for the segregation of sick people, suspected illnesses and contagion suspects and the designation of houses and apartments, version of March 6, 2020. In: RIS, Federal law consolidated. January 31, 2020, accessed on March 6, 2020 : "In the case of measles or infection with 2019-nCoV ('2019 novel coronavirus'), the sick and suspected diseases must be segregated or, depending on the circumstances of the case, only subjected to certain traffic restrictions." 
372. ↑ Ordinance of January 31, 2020. 21. Ordinance of the Federal Minister for Social Affairs, Health, Care and Consumer Protection, with which the ordinance of the Minister of the Interior in agreement with the Minister of Education and Culture of February 22, 1915, regarding the segregation of the sick, Disease suspect and contagion suspect and the names of houses and apartments will be changed. In: Federal Law Gazette for the Republic of Austria . January 31, 2020, accessed on March 6, 2020 : "In § 4 3rd sentence, the word sequence 'or infection with 2019-nCoV (' 2019 novel coronavirus ')' is inserted after the word 'measles'." 
373. ↑ New Coronavirus: Information for Health Professionals. Suspicion and reporting criteria as well as reporting form. Federal Office of Public Health , March 5, 2020, accessed on March 5, 2020 . 
374. ↑ Federal Act on Combating Communicable Diseases in Humans. Epidemics Act, EpG. Federal Chancellery, January 1, 2017, accessed on March 6, 2020 : “Art. 13 Regulation of reports " 
375. ^ Ordinance on combating communicable diseases in humans. (Epidemic Ordinance, EpV) of April 29, 2015 (as of March 1, 2019). Federal Chancellery, accessed on March 6, 2020 : “Art. 19 Further regulations by the EDI " 
376. ^ Ordinance of the EDI on the reporting of observations of communicable diseases in humans. dated December 1, 2015 (as of February 1, 2020). Federal Chancellery, accessed on March 6, 2020 : "32a Novel Coronavirus (2019-nCoV)" 
377. ↑ Registration forms. COVID-19 notification. Federal Office of Public Health, March 24, 2020, accessed on March 31, 2020 . 
378. ↑ ICD-10 (WHO and GM): U07.1 codes COVID-19, coronavirus disease-2019. German Institute for Medical Documentation and Information (DIMDI), February 17, 2020, accessed on May 14, 2020 . 
379. ↑ ICD-10-GM 2020: New U-code U99.0! and new coding question for testing for SARS-CoV-2. DIMDI, May 25, 2020, accessed on May 27, 2020 . 
380. ↑ Is U07.2! to be coded in people who are not suspected of being infected with SARS-CoV-2, but a test for SARS-CoV-2 has been carried out which turns out negative? (ICD-10-GM No. 1019). DIMDI, accessed on May 27, 2020 . 
381. ↑ ICD-10-GM 2020: Further new U-codes in connection with COVID-19 published. Retrieved January 18, 2021 . 
382. ↑ Federal Statistical Office: Official Communication 2021 No. 1 - Coding COVID-19 - To be used in cases with an exit date from January 1, 2021 | Publication. December 3, 2020, accessed January 18, 2021 . 
383. ↑ ICD-10-GM 2021: New U-codes in connection with vaccinations against COVID-19 published. Retrieved April 24, 2021 . 
384. ↑ Trade association raw materials and chemical industry: Information on the new coronavirus (SARS-CoV-2). bgrci.de, accessed on March 31, 2020 . Information on the new coronavirus (SARS-CoV-2) ( Memento from April 8, 2020 in the Internet Archive ) 
385. ↑ A veterinarian informs: Coronaviruses can be dangerous for dogs and cats. In: Frankfurter Neue Presse . March 6, 2020, accessed April 5, 2020 . 
386. ↑ ^{a b} Q&A on coronaviruses (COVID-19). World Health Organization , March 9, 2020, accessed April 5, 2020 . 
387. ↑ Juliane Gutmann: Covid-19: Can pets transmit the coronavirus? In: Münchner Merkur . March 6, 2020, accessed March 6, 2020 . 
388. ↑ ^{a b c} Coronavirus: No, dogs do not get Covid-19. In: The mirror. March 3, 2020, accessed March 6, 2020 . 
389. ↑ Information received on 01/03/2020 from Dr Thomas Sit, Chief Veterinary Officer. World Organization for Animal Health , March 1, 2020, accessed April 5, 2020 . Information received on 01/03/2020 from Dr Thomas Sit, Chief Veterinary Officer ( Memento from March 2, 2020 in the Internet Archive ) 
390. ↑ A cat is infected with the coronavirus. In: New Westphalian . March 29, 2020, accessed March 29, 2020 . 
391. ^ Qiang Zhang et al .: A serological survey of SARS-CoV-2 in cat in Wuhan . In: Emerging Microbes & Infections . tape 9 , no. 1 , January 2020, p. 2013-2019 , doi : 10.1080 / 22221751.2020.1817796 , PMID 32867625 , PMC 7534315 (free full text): "Cat is susceptible to SARS-CoV-2. [...] Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats "
392. ↑ Young-Il Kim et al. : Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. In: Cellpress-Preprint doi: 10.1016 / j.chom.2020.03.023 ( full text as PDF ).
393. ↑ Jianzhong Shi et al. : Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. In: Science. doi: 10.1126 / science.abb7015 ( full text as PDF ).
394. ↑ Nadja Podbregar: First gorillas infected with the coronavirus - great apes in the San Diego Zoo have contracted Covid-19. On: scinexx.de from January 12, 2021.
395. ↑ Outbreak in the mink farm - Thousands of minks perished due to corona infection. In: faz.net. October 9, 2020, accessed October 10, 2020 . 
396. ↑ foedevarestyrelsen.dk (English)
397. ↑ Danmarks Radio : Tredje Minkfarm i Nordjylland ramt af corona. On: dr.dk from July 1, 2020.
398. ↑ Udbrud i Hjørring: Collect virus mutation found at mink, minkavler and på plejehjem. (Translated outbreak in Hjørring: Same virus mutation in mink, mink breeders and a nursing home ) On: dr.dk from June 19, 2020.
399. ↑ Denmark is killing all mink out of concern about the corona virus: Millions of minks have to die because of corona. On: Stuttgarter Zeitung . November 5, 2020, accessed November 5, 2020.
400. ↑ Reuters Staff: Denmark to impose tight regional lockdown after spread of mink coronavirus mutation . In: Reuters . November 5, 2020 ( reuters.com [accessed November 5, 2020]).
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402. ↑ Stephanie Pappas: Endangered ferrets get experimental COVID-19 vaccine. On: livescience.com from January 1, 2021.
403. ↑ After mass killings in Denmark - Finland develops corona vaccination for mink. On: n-tv from January 12, 2021
404. ↑ Crucial test phase is running - Russia is developing corona vaccine for animals. On: n-tv from December 13, 2020.

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