MERS-CoV

from Wikipedia, the free encyclopedia
Middle East respiratory syndrome coronavirus (MERS-CoV)
MERS-CoV (8717564410) .jpg

MERS-CoV virus particles (colored yellow) under the transmission electron microscope

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Pisuviricota
Class : Pisoniviricetes
Order : Nidovirals
Subordination : Cornidovirineae
Family : Coronaviridae
Subfamily : Coronavirinae
Genre : Beta coronavirus
Subgenus : Merbecovirus
Type : Middle East respiratory syndrome-related coronavirus
Taxonomic characteristics
Genome : (+) ssRNA linear
Baltimore : Group 4
Symmetry : helical
Cover : available
Scientific name
Middle East respiratory syndrome-related coronavirus
Short name
MERS-CoV
Left
NCBI  Taxonomy: 1335626
ICTV Taxon History: 201851864

MERS-CoV ( scientifically Middle East respiratory syndrome-related coronavirus ) is a virus from the coronavirus family that was first identified in 2012 , which can cause severe respiratory infections , pneumonia and kidney failure in humans. So far, all infections had their origin in the Arabian Peninsula, with a focus on Saudi Arabia . The diseases that became known to the health authorities were mostly severe and often fatal; however, it is not known what proportion of infected people will develop the disease. Based on the previous epidemiological pattern of the spread, it can be assumed that the MERS-CoV is only transmitted with difficulty from person to person and that the primary host organisms are probably bats , from which it is sporadically transmitted to people via dromedaries as intermediate hosts .

So far there is no proven and safe antiviral therapy . Treatment of the sick is therefore limited to alleviating the symptoms. Travel warnings or trade restrictions have not yet been expressly endorsed by the WHO (as of January 2016).

An official Germanized name has not yet existed for either the virus or the clinical picture; Literally translated, the abbreviation MERS-CoV stands for "Middle East Respiratory Syndrome Coronavirus". The acronym MERS-CoV was modeled on the name of the related virus SARS-CoV - the causative agent of severe acute respiratory syndrome (SARS).

discovery

In June 2012, a patient in London died of an acute, severe respiratory disease who had been moved from his hometown of Jeddah in Saudi Arabia to the UK for intensive care with these respiratory symptoms . In addition, he developed acute kidney failure at a very early stage of the disease . An uncharacteristic form of pneumonia ( atypical pneumonia ) suggested, among other things, a virus infection. After all the usual virological detection methods for known respiratory viruses remained unsuccessful, the search with non- species- specific methods (Pan-Corona-PCR), which had already been developed when the SARS coronavirus was identified in 2002, found a gene segment from a previously unknown Coronavirus can be detected.

At the beginning of September 2012, another patient in Qatar fell ill with a severe respiratory infection and an additional acute kidney failure. This patient was also transferred to London for further treatment. He was in Saudi Arabia shortly before the first symptoms appeared. The virus, which was first found in June 2012, could also be identified in this patient. The sequenced gene fragments of the viruses isolated from these two patients at an interval of three months almost matched, so that it was assumed that the coronavirus had newly emerged in the human population. Due to the sequence similarity , the newly emerged virus was provisionally assigned to the genus Betacoronavirus (now HCoV-EMC, EMC: Erasmus Medical Center ).

By the end of November 2012, nine cases of illness with the new virus were known, all of which had their origins in the Arabian Peninsula (five cases in Saudi Arabia, two in Qatar) or in the Middle East ( also two in Jordan ); of the nine sufferers, five had died by then. The two cases recognized from Jordan come from a group of pneumonia from April 2012, which were subsequently identified on the basis of stored samples in the consultative laboratory of the World Health Organization (WHO) in Cairo . Both patients fell ill in spring 2012 and died shortly afterwards of pneumonia.

At the beginning of July 2013, the World Health Organization (WHO) convened the Emergency Committee, made up of scientists from various disciplines, "as a result of the growing international concern about MERS-CoV" , which will provide advice to the WHO Directorate-General. A health emergency of international scope was not established.

Systematics

MERS-CoV was provisionally assigned to the genus Betacoronavirus as an unclassified species on the basis of sequence comparisons of the viral genomes . Within the genus it shows a close relationship to two species of coronaviruses in bats, the BatCoV-HKU5 and BatCoV-HKU4. These belong to the so-called cluster 2c within the genus. It differs significantly from the human pathogenic beta coronaviruses SARS-CoV , HCoV-OC43 and HCoV-HKU1 at the level of the genome sequence. So far, the isolate "Betacoronavirus England 1" has been described within the species MERS-CoV.

Initially, the virus was referred to as human beta coronavirus 2c EMC / 2012 ( HCoV-EMC ), human coronavirus EMC and also as "new coronavirus" (NCoV). The Coronavirus Study Group of the International Committee on Taxonomy of Viruses finally announced on May 15, 2013 that the official name of the virus is Middle East respiratory syndrome coronavirus (MERS-CoV) .

Disease emergence

The beta coronavirus has on its surface a protein with the English name spike ( sting ), thus it to the on human lung cells contained protein dipeptidyl peptidase 4 docks (DPP4). How tightly the virus binds to this receptor determines whether the virus can then penetrate the cell in question and infect it with it.

Researchers at the National Institute of Health in Hamilton, Montana, found through studies on rhesus monkeys that the virus appears to only multiply in certain cells deep in the lungs. This could be an explanation for the severity of the illnesses as well as for the low transferability of the virus from person to person.

In analogy to other coronaviruses and respiratory viruses, after the discovery of the first diseases it was considered very likely that MERS-CoV is also transmitted by droplet infection and smear infection . Respiratory secretions from the nose and the upper respiratory tract of infected people are important, which are passed on through speaking , sneezing , coughing and contaminated hands. In a patient from Abu Dhabi who was treated in Germany , these assumptions were finally confirmed: The greatest viral load was found in the patient's lower respiratory tract, the doctors found lower amounts of pathogen in the urine and stool ; The patient died in Munich in March 2013 after pneumonia and kidney failure of blood poisoning and multiple organ failure .

Fragments of viral genetic material were also found in the air of a stable in which infected dromedaries were staying. The fragments were identical to both virus samples from the infected dromedaries and virus samples from the stable owner infected with MERS-CoV.

The incubation period is usually less than a week, but individual cases of nine to twelve days have also been observed.

The World Health Organization recommends that people with significant pre-existing conditions such as diabetes mellitus or chronic obstructive pulmonary disease , with immunodeficiency or previous kidney failure , stay away from camels, do not drink camel raw milk and avoid other food that may be contaminated by camels.

Coronaviruses are already inactivated by soap and other detergents when washing hands or washing clothes.

Animal reservoir

MERS-CoV particles (stained green) on camel epithelial cells
MERS-CoV particles (colored yellow) on kidney epithelial cells of a green monkey

From the cases observed in 2012, which occurred with a large time lag between the illnesses and which usually did not result in any cases of illness in direct contact persons of the sick, it could be concluded that the MERS-CoV is not transmitted very efficiently from person to person and that there is very likely an animal pathogen reservoir located on the Arabian Peninsula , from which the sporadic cases originate. Animal reservoirs such as bats are very typical for coronaviruses, but it is considered unlikely that the virus will be transmitted directly from bats to humans. The most likely reservoir hosts and vectors were dromedaries named. When examining dromedary serum samples from Saudi Arabia, which had been archived from 1983 onwards, specific MERS-CoV antibodies could be detected, while they were not detectable in the populations of domesticated goats and sheep. When examining current dromedary populations in 2013, specific antibodies were detected in up to 74% of the animals, depending on the herds examined. In camels the infection is mild with symptoms such as high temperature and runny nose .

Finally, the virus was also detected directly using the polymerase chain reaction (PCR). A particularly high virus concentration was detected in swabs of the nasal mucosa : The dromedaries examined in Oman and Qatar carried distinguishable virus variants, and these local variants were each largely identical to the variants circulating in the same area in infected people. The viruses were also detected in camel populations in Kuwait by PCR, and in Iran from the nasal swab of camels that had been illegally exported from Pakistan to Iran.

Young dromedaries in particular, who are only contagious for a few days, are acutely ill. It was concluded from this that camels under two years of age pose a particularly high risk of infection.

A comparison of RNA - nucleotide sequence of MERS virus with the nucleotide sequence of MERS-like virus HKU4 of bats - that can not pass to humans - showed that only two mutations are needed to the MERS-like bat virus infectious to Make people. Until 2019, however, MERS-CoV was only detected in camels and not in any other animal hosts.

distribution

Veterinary examination

March 2013 to March 2014

At the end of March 2013, the World Health Organization was aware of 17 diseases, including 11 deaths and two documented human-to-human transmission; After close contact with an infected person, the virus had been transmitted to contact persons who also had an immunodeficiency due to another non-infectious disease - and thus a reduced resistance to infection. At the end of May 2013, the WHO received reports on 50 patients, 30 of whom had died; The infected were mainly in Saudi Arabia , but also in Jordan , Qatar and the United Arab Emirates , and there were other human-to-human transmissions in France , Italy , Tunisia and the United Kingdom . These transfers from the first infected person ( index patient ) to contact persons (first passages) took place with family members, work colleagues or in the hospital, but the pathogens were not passed on from the infected contact persons to other people in their social environment (second passages).

At the end of March 2014, the WHO had reports on 206 sick people, of whom 86 had died.

April 2014 to March 2015

Further diseases spread from the Arabian Peninsula to other countries were in April 2014 from Greece , Malaysia , Egypt and the USA , in May 2014 from the Netherlands , in September 2014 from Austria , in October 2014 from Turkey , in June 2015 from Thailand and known from the Philippines in July 2015 . Furthermore, an infection had become known from Yemen for the first time , and previous illnesses from Kuwait and Oman were confirmed, so that by May 2014 at the latest, all states on the peninsula had reported primary infections to the WHO. In April 2014, there was also massive transfer of the virus from patients to nursing staff and doctors in several hospitals in Saudi Arabia. One of the consequences of this was that the Saudi health minister was dismissed; he was accused of playing down the infection. The accumulation of infections in Jeddah and Riyadh was later attributed to inadequate hygiene measures in the hospitals.

In Osnabrück , the disease was detected in a 65-year-old man who returned from a vacation trip to Abu Dhabi in early February 2015 . The man died in early June 2015 of a coronavirus-related illness.

At the end of March 2015, the WHO had reports on 1,102 sick people, of whom 416 had died.

April 2015 to March 2016

Number of registered MERS cases between May and July 2015 in South Korea .
yellow: sick people in treatment
red: deceased persons
blue: healed infected people

According to the WHO of July 21, 2015, at least 186 people (36 of whom died) fell ill in South Korea between mid-May and mid-July 2015 after the index patient of this outbreak returned to his home country from the Arabian Peninsula and had visited several hospitals there; one of the sick people, who had been in close contact with the index patient in Korea and had left the country against medical advice, developed the symptoms of the infection in the People's Republic of China . Among the people infected in Korea were at least two who had no contact with the index patient; these were the first observed human-to-human-to-human transmissions (second passages) of the viruses. The infection incidence in Korea was limited to hospitals, i.e. to transmissions from patients to close relatives, to bed neighbors and medical staff, since the doctors - according to the WHO - recognized the first viral diseases too late, whereupon the viruses spread, especially due to hygienic deficiencies the two hospitals could spread.

As of March 23, 2016, the WHO reported 1698 patients, of which at least 609 had died. The evaluation of blood samples from asymptomatic residents of Saudi Arabia, however, revealed indications that tens of thousands of people in this country alone were infected with the MERS virus without this infection being followed by a noticeable disease.

Experts assume that part of the observed changes in the infection rate can be attributed to the fact that the number of virus tests in Saudi Arabia has increased significantly since April 2014.

Infection incidence since April 2016

In contrast to the previous year, the number of infections in 2016 was somewhat more moderate. As of September 21, 2016, the WHO reported 1806 patients, of whom at least 643 had died; By December 2, 2016, the number of sick people increased to 1,841 and the number of deceased to at least 652 people. After that, too, there were repeated local outbreaks - especially in Saudi Arabia - that indicated continued inadequate hygiene measures in a hospital in Riyadh , so that by June 19, 2017, a total of 2029 infections and at least 704 deaths were reported to the WHO. On October 9, 2017, the WHO was aware of 2,090 people, 730 of whom did not survive the infection; Among these new cases were again several dozen employees of the Saudi health service.

On January 26, 2018, the WHO reported 2143 patients, 750 of whom had died, and in the following months it may also occur. a. again to two outbreaks in Saudi Arabian hospitals, so that by August 31, 2018 a total of 2241 infections had been reported to the WHO (1865 of them from Saudi Arabia) and a total of 795 deaths caused by MERS-CoV. On October 30, 2018, the WHO was aware of 2,266 diseases, of which 804 led to death, at the end of February 2020 the WHO was known to 2,519 diseases, of which 866 led to death.

illness

The disease (MERS, Middle East respiratory syndrome ) often starts with fever , cough , sputum and shortness of breath . The Robert Koch Institute describes the typical course of the disease as follows: “Clinically proven cases present themselves at the beginning with an acute, flu-like illness. The incubation period is usually one to two weeks. If the course is severe, pneumonia can develop, which can turn into acute respiratory distress syndrome . A common accompanying symptom is diarrhea ; if the course is severe, kidney failure can also occur. Severe courses predominantly occur in people with chronic previous illnesses, such as Such as diabetes , cancer or immunosuppression . ”Pneumonia can make the patient's condition so worse that treatment in the intensive care unit becomes necessary. There are also people who have had a previous infection but did not develop a disease.

It is currently unclear whether the virus can develop into a more effective transmission due to frequent host passages in humans and thus adapt to humans as a new host. So far, no mutations indicating an adaptation have been found. However, on April 23, 2014, the WHO expressed "concern" about the steadily increasing number of infections, since 75 percent of the transmission had been from person to person in the previous weeks.

Virus detection and therapy in humans

Test procedures for the direct detection of a coronavirus infection in humans, some of which have so far been used in virological laboratories for routine respiratory infections, do not cover the MERS-CoV. Based on the previously known genome sequences, MERS-CoV-specific, direct pathogen detection using a polymerase chain reaction from throat swabs, but preferably from BAL fluid, is possible in specialized laboratories of the virological institutes . The target sequences of the MERS-CoV-specific RNA detection are gene segments in front of the gene for the envelope protein E ( upstream E ) and the ORF-1b gene.

In acute illness, the virus can be detected in high concentrations in respiratory samples, and in low concentrations it is also found in blood serum . Cultivation in cell cultures is possible, but has no diagnostic significance. Serological methods for the detection of antibodies are only available to a limited extent and, as with all acute respiratory virus infections, have no informative value with regard to the specific detection of infection. At MERS-CoV, experimental antibody detection is available as Western blot or immunofluorescence tests with cell cultures for scientific questions and for assessing the immune response.

So far there is no proven and safe antiviral therapy, the treatment of the sick is therefore limited to the alleviation of the symptoms. However, initial experiments with rhesus monkeys , which are currently the only model organisms for MERS infections, indicated that a combination of interferon-α2b and ribavirin could lower the viral load; Both active ingredients have been used routinely for the treatment of hepatitis C for some time . Other active ingredients that have already been approved as medicinal products are also being tested for possible additional benefits for MERS patients.

Various research institutions have been working on the development of vaccines for use on humans for some time. A mouse model for testing a potential antiviral therapy was also published in 2014. In 2014, an in vitro inhibition of double vesicle formation by coronaviruses and thus of RNA synthesis by the benzamide compound K22 was demonstrated. In the mouse model, passive immunization through the transfer of antibodies from infected dromedaries was shown to be effective. The results of the first two Phase I studies on vaccinated test persons were published in April 2020; in the Deutsches Ärzteblatt it said: “Both vaccines have passed the safety test. Both got an immune response. It is still unclear whether it is sufficient to protect people from infection. "

A vaccine tested on four camels, the effectiveness of which was published in Science at the end of 2015 , reduced the excretion of viruses from the nasopharynx without, however, completely preventing their excretion.

Reporting requirement

In Germany, direct or indirect evidence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) must be reported by name in accordance with Section 7 of the Infection Protection Act (IfSG), provided the evidence indicates an acute infection. This reporting obligation for the pathogen primarily affects laboratories and their lines (cf. § 8 IfSG).

In Austria suspicion, illness and deaths are on MERS-CoV in accordance with § 1 1 para. 1 number Epidemics Act 1950 subject to notification . Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Switzerland, doctors, hospitals, etc. are obliged to report in the event of clinical suspicion, the initiation of pathogen-specific laboratory diagnostics and an epidemiological connection due to the MERS coronavirus . This results from the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Appendix 1 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans . In addition, the positive and negative laboratory analytical findings for a MERS coronavirus must be reported according to the EpG i. V. m. the Epidemics Ordinance and ( Annex 3 ) of the above-mentioned EDI Ordinance; this reporting requirement is aimed at laboratories.

See also

literature

  • AM Zaki et al .: Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. In: The New England Journal of Medicine . Vol. 367, No. 19, 2012, pp. 1814-1820 (Epub October 17, 2012), PMID 23075143 , doi: 10.1056 / NEJMoa1211721 (full text, PDF; 556 kB - first description).
  • S. Perlman, J. Zhao: Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus. In: MBio. January 15, 2013, Vol. 4, No. 1, PMID 23322635 .
  • MA Müller et al .: Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. In: MBio. December 11, 2012, Vol. 3, No. 6, PMID 23232719 .
  • KV Holmes, SR Dominguez: The new age of virus discovery: genomic analysis of a novel human betacoronavirus isolated from a fatal case of pneumonia. In: MBio. January 8, 2013, Vol. 4, No. 1, PMID 23300251 .
  • S. van Boheemen S et al .: Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. In: MBio. November 20, 2012, Vol. 3, No. 6, PMID 23170002 .
  • E. Kindler et al .: Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential. In: MBio. 2013, Vol. 4, No. 1, pp. E611 – e612. doi: 10.1128 / mBio.00611-12 .

Web links

Commons : MERS  - collection of images, videos and audio files

Individual evidence

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    South Korean MERS cluster grows; Saudi Arabia reports case. On: cidrap.umn.edu from May 28, 2015
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