MERS


Middle East respiratory syndrome is a viral respiratory infection caused by Middle East respiratory syndrome–related coronavirus. Symptoms may range from none, to mild, to severe depending on age and risk level. Typical symptoms include fever, cough, diarrhea, and shortness of breath. The disease is typically more severe in those with other health problems.
The first case was identified in June 2012 by Egyptian physician Ali Mohamed Zaki at the Dr. Soliman Fakeeh Hospital in Jeddah, Saudi Arabia, and most cases have occurred in the Arabian Peninsula. Over 2,600 cases have been reported as of January 2021, including 45 cases in the year 2020. About 35% of those who are diagnosed with the disease die from it. Larger outbreaks have occurred in South Korea in 2015 and in Saudi Arabia in 2018.
MERS-CoV is a virus in the coronavirus family believed to be originally from bats. However, humans are typically infected from camels, either during direct contact or indirectly through respiratory droplets. Spread between humans typically requires close contact with an infected person. Its spread is uncommon outside of hospitals. Thus, its risk to the global population is currently deemed to be significantly low. Diagnosis is by rRT-PCR testing of blood and respiratory samples.
There is no specific vaccine or treatment for the disease, but a number are being developed. The World Health Organization recommends that those who come in contact with camels wash their hands and not touch sick camels. They also recommend that camel-based food products be appropriately cooked. Treatments that help with the symptoms and support body functioning may be used.
Previous infection with MERS can confer cross-reactive immunity to SARS-CoV-2 and provide partial protection against COVID-19. However, co-infection with SARS-CoV-2 and MERS is possible and could lead to a recombination event.

Signs and symptoms

Early reports compared the viruses to severe acute respiratory syndrome, and it has been referred to as Saudi Arabia's SARS-like virus. The first person, in June 2012, had a fever, cough, expectoration, and shortness of breath. One review of 47 laboratory confirmed cases in Saudi Arabia gave the most common presenting symptoms as fever in 98%, cough in 83%, shortness of breath in 72% and myalgia in 32% of people. There were also frequent gastrointestinal symptoms with diarrhea in 26%, vomiting in 21%, abdominal pain in 17% of people. 72% of people required mechanical ventilation. There were also 3.3 males for every female. One study of a hospital-based outbreak of MERS had an estimated incubation period of 5.5 days. MERS can range from asymptomatic disease to severe pneumonia leading to acute respiratory distress syndrome. Kidney failure, disseminated intravascular coagulation, and pericarditis have also been reported.

Cause

Virology

Middle East respiratory syndrome is caused by the MERS coronavirus, a species with single-stranded RNA belonging to the genus betacoronavirus which is distinct from SARS coronavirus and the common-cold coronavirus. Its genomes are phylogenetically classified into two clades, Clades A and B. Early cases of MERS were of Clade A clusters, while new cases are genetically different in general. The virus grows readily on Vero cells and LLC-MK2 cells. In November 2012, Egyptian virologist Dr. Ali Zaki sent a virus sample from the first confirmed case in Saudi Arabia to virologist Ron Fouchier, a leading coronavirus researcher at the Erasmus Medical Center in Rotterdam, the Netherlands. The second laboratory-proven case was in London, confirmed by the UK Health Protection Agency. The HPA named the virus the London1_novel CoV 2012.

Transmission

Camels

A study performed between 2010 and 2013, in which the incidence of MERS was evaluated in 310 dromedary camels, revealed high titers of neutralizing antibodies to MERS-CoV in the blood serum of these animals. A further study sequenced MERS-CoV from nasal swabs of dromedary camels in Saudi Arabia and found they had sequences identical to previously sequenced human isolates. Some individual camels were also found to have more than one genomic variant in their nasopharynx. There is also a 2014 report of a Saudi Arabian man who became ill seven days after applying topical medicine to the noses of several sick camels and later he and one of the camels were found to have identical strains of MERS-CoV. It is still unclear how the virus is transmitted from camels to humans. In 2014, the Saudi Ministry of Agriculture advised people to avoid contact with camels or wear breathing masks when around them. In response "some people have refused to listen to the government's advice" and kiss their camels in defiance of their government's advice. In 2020, the World Health Organization advised avoiding contact with camels and to eat only fully cooked camel meat, pasteurized camel milk, and to avoid drinking camel urine.

Between people

There has been evidence of limited, but not sustained spread of MERS-CoV from person to person, both in households as well as in health care settings like hospitals. Most transmission has occurred "in the circumstances of close contact with severely ill persons in healthcare or household settings" and there is no evidence of transmission from asymptomatic cases. Cluster sizes have ranged from 1 to 26 people, with an average of 2.7.

Diagnosis

According to World Health Organization, the interim case definition is that a confirmed case is identified in a person with a positive lab test by "molecular diagnostics including either a positive polymerase chain reaction on at least two specific genomic targets or a single positive target with sequencing on a second".

World Health Organization

According to the WHO, a probable case is:
  • A person with a fever, respiratory infection, and evidence of pneumonia or acute respiratory distress syndrome, where testing for MERS-CoV is unavailable or negative on a single inadequate specimen, and the person has a direct link with a confirmed case
  • A person with an acute febrile respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease, an inconclusive MERS-CoV laboratory test, and a resident of or traveler to Middle Eastern countries where MERS-CoV virus is believed to be circulating in the 14 days before onset of illness
  • A person with an acute febrile respiratory illness of any severity, an inconclusive MERS-CoV laboratory test, and a direct epidemiologic link with a confirmed MERS-CoV case

    Centers for Disease Control

In the United States, the Centers for Disease Control and Prevention recommend investigating any person with:
  • Fever and pneumonia or acute respiratory distress syndrome and either:
  • * a history of travel from countries in or near the Arabian Peninsula within 14 days before symptom onset, or
  • * close contact with a symptomatic traveler who developed fever and acute respiratory illness within 14 days after traveling from countries in or near the Arabian Peninsula or
  • * a member of a cluster of people with severe acute respiratory illness of unknown cause in which MERS-CoV is being evaluated, in consultation with state and local health departments.
  • Fever and symptoms of respiratory illness and being in a healthcare facility within 14 days before symptom onset in a country or territory in or near the Arabian Peninsula in which recent healthcare-associated cases of MERS have been identified.
  • Fever or symptoms of respiratory illness and close contact with a confirmed MERS case while the case was ill.

    Medical imaging

findings tend to show bilateral patchy infiltrates consistent with viral pneumonitis and acute respiratory distress syndrome. Lower lobes tend to be more involved. CT scans show interstitial infiltrates.

Laboratory testing

MERS cases have been reported to have low white blood cell count, and in particular low lymphocytes. For PCR testing, the World Health Organization recommends obtaining samples from the lower respiratory tract via bronchoalveolar lavage, sputum sample or tracheal aspirate as these have the highest viral loads. There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.
Several highly sensitive, confirmatory real-time RT-PCR assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE, open reading frame 1B and open reading frame 1A. The WHO recommends the upE target for screening assays as it is highly sensitive. In addition, hemi-nested sequencing amplicons targeting RdRp and nucleocapsid gene fragments can be generated for confirmation via sequencing. Reports of potential polymorphisms in the N gene between isolates highlight the necessity for sequence-based characterization.
The WHO recommended testing algorithm is to start with an upE RT-PCR and if positive confirm with ORF 1A assay or RdRp or N gene sequence assay for confirmation. If both an upE and secondary assay are positive it is considered a confirmed case.
Protocols for biologically safe immunofluorescence assays have also been developed; however, antibodies against betacoronaviruses are known to cross-react within the genus. This effectively limits their use to confirmatory applications. A more specific protein-microarray based assay has also been developed that did not show any cross-reactivity against population samples and serum known to be positive for other betacoronaviruses. Due to the limited validation done so far with serological assays, WHO guidance is that "cases where the testing laboratory has reported positive serological test results in the absence of PCR testing or sequencing, are considered probable cases of MERS-CoV infection, if they meet the other conditions of that case definition."