The virus MERS-CoV is a member of the beta group of coronavirus,
Betacoronavirus, lineage C. MERS-CoV genomes are phylogenetically classified into two
clades, clade A and B. The earliest cases were of clade A clusters, while the majority of more recent cases are of the genetically distinct clade B. MERS-CoV is one of seven known coronaviruses to infect humans, including
HCoV-229E,
HCoV-NL63,
HCoV-OC43,
HCoV-HKU1, the original
SARS-CoV (or SARS-CoV-1), and
SARS-CoV-2. By November, 2019, 2,494 cases of MERS had been reported with 858 deaths, implying a
case fatality rate of greater than 30%.
Early cases and spillover event The first confirmed case was reported in Jeddah, Saudi Arabia in June 2012.
Egyptian virologist Ali Mohamed Zaki isolated and identified a previously unknown coronavirus from the man's
lungs. Zaki then posted his findings on 24 September 2012 on
ProMED-mail. Cells inoculated with the isolated virus showed
cytopathic effects (CPE), in the form of rounding and
syncytia formation.
Tropism In humans, the virus has a strong
tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize
interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells. Due to the clinical similarity between MERS-CoV and
SARS-CoV-1, it was proposed that they may use the same cellular receptor; the exopeptidase, angiotensin converting enzyme 2 (
ACE2). However, it was later discovered that neutralization of ACE2 by recombinant antibodies does not prevent MERS-CoV infection. Further research identified dipeptidyl peptidase 4 (
DPP4; also known as
CD26) as a functional cellular receptor for MERS-CoV. Bat DPP4 genes appear to have been subject to a high degree of adaptive evolution as a response to coronavirus infections, so the lineage leading to MERS-CoV may have circulated in bat populations for a long period of time before being transmitted to people.
Transmission On 13 February 2013, the
World Health Organization stated that "the risk of sustained person-to-person transmission appears to be very low." The cells MERS-CoV infects in the lungs only account for 20% of respiratory epithelial cells, so a large number of virions are likely needed to be inhaled to cause infection. However, the infection of healthcare workers has led to concerns of human to human transmission. The
Centers for Disease Control and Prevention (CDC) list MERS as transmissible from human to human. They state that "MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed. Clusters of cases in several countries are being investigated." However, on the 28th of May, the CDC revealed that the Illinois man who was originally thought to have been the first incidence of person-to-person spread (from the Indiana man at a business meeting), had in fact tested negative for MERS-CoV. After completing additional and more definitive tests using a neutralising antibody assay, experts at the CDC concluded that the Indiana patient did not spread the virus to the Illinois patient. Tests concluded that the Illinois man had not been previously infected. It is possible for MERS to be symptomless, and early research has shown that up to 20% of cases show no signs of active infection but have MERS-CoV antibodies in their blood.
Evolution The virus appears to have originated in bats. The virus itself has been isolated from a bat. This virus is closely related to the
Tylonycteris bat coronavirus HKU4 and
Pipistrellus bat coronavirus HKU5. Serological evidence shows that these viruses have infected camels for at least 20 years. The most recent common ancestor of several human strains has been dated to March 2012 (95% confidence interval December 2011 to June 2012). It is thought that the viruses have been present in bats for some time and had spread to camels by the mid-1990s. The viruses appear to have spread from camels to humans in the early 2010s. The original bat host species and the time of initial infection in this species has yet to be determined. Examination of the sequences of 238 isolates suggested that this virus has evolved into three clades differing in
codon usage, host, and geographic distribution. In early 2022, a new MERS-related Coronavirus, NeoCoV, was identified in
Neoromicia bats in
South Africa. While MERS-CoV and a handful of other related bat Coronaviruses use
DPP4 to enter host cells, NeoCoV and another close relative, PDF-2180-CoV, were found to be able to use some forms of bat and human
ACE2 receptors for entry, the same receptor used for entry by
SARS-related viruses. Researchers uncovered a molecular determinant near the virus's binding interface, around the Asp338 residue, which keeps the virus from being able to use Human ACE2 for infection; however, NeoCoV viruses with a T501F mutation in their
receptor binding domain (RBD) motif were able to effectively infect human ACE2-expressing cells. Researchers were concerned by the virus's properties and identified NeoCoV as a potential pandemic risk, with one study stating that if NeoCoV triggered a pandemic, it could have a lethality rate of 30%, a level similar to that of MERS. Work by epidemiologist Ian Lipkin of
Columbia University in New York showed that the virus isolated from a bat looked to be a match to the virus found in humans. 2c betacoronaviruses were detected in
Nycteris bats in Ghana and
Pipistrellus bats in Europe that are phylogenetically related to the MERS-CoV virus. However the major natural reservoir where humans get the virus infection remained unknown until on 9 August 2013, a report in the journal
The Lancet Infectious Diseases showed that 50 out of 50 (100%)
blood serum from
Omani camels and (14%) from Spanish camels had protein-specific antibodies against the MERS-CoV spike protein. Blood serum from European sheep, goats, cattle, and other camelids had no such antibodies. Soon afterward, on 5 September 2013, a seroepidemiological study published in the journal of
Eurosurveillance by R.A Perera
et al. where they investigated 1343 human and 625 animal sera indicated, the abundant presence of MERS-CoV specific antibody in 108 out of 110 Egyptian dromedary camels but not in other animals such as goats, cows or sheep in this region. At least one person who has fallen sick with MERS was known to have come into contact with camels or recently drank
camel milk. Countries like
Saudi Arabia and the
United Arab Emirates produce and consume large amounts of
camel meat. The possibility exists that African or Australian
bats harbor the virus and transmit it to camels. Imported camels from these regions might have carried the virus to the Middle East. In 2013, MERS-CoV was identified in three members of a dromedary camel herd held in a Qatar barn, which was linked to two confirmed human cases who have since recovered. The presence of MERS-CoV in the camels was confirmed by the
National Institute of Public Health and Environment (RIVM) of the Ministry of Health and the
Erasmus Medical Center (WHO Collaborating Center), the Netherlands. None of the camels showed any sign of disease when the samples were collected. The Qatar Supreme Council of Health advised in November 2013 that people with underlying health conditions, such as heart disease, diabetes, kidney disease, respiratory disease, the immunosuppressed, and the elderly, avoid any close animal contacts when visiting farms and markets, and to practice good hygiene, such as washing hands. A further study on dromedary camels from Saudi Arabia published in December 2013 revealed the presence of MERS-CoV in 90% of the evaluated dromedary camels (310), suggesting that dromedary camels not only could be the main reservoir of MERS-CoV, but also the animal source of MERS. According to the 27 March 2014 MERS-CoV summary update, recent studies support that camels serve as the primary source of the MERS-CoV infecting humans, while bats may be the ultimate reservoir of the virus. Evidence includes the frequency with which the virus has been found in camels to which human cases have been exposed, seriological data which shows widespread transmission in camels, and the similarity of the camel CoV to the human CoV. On 6 June 2014, the
Arab News newspaper highlighted the latest research findings in the New England Journal of Medicine in which a 44-year-old Saudi man who kept a herd of nine camels died of MERS in November 2013. His friends said they witnessed him applying a topical medicine to the nose of one of his ill camels—four of them reportedly sick with nasal discharge—seven days before he himself became stricken with MERS. Researchers sequenced the virus found in one of the sick camels and the virus that killed the man, and found that their genomes were identical. In that same article, the
Arab News reported that as of 6 June 2014, there have been 689 cases of MERS reported within the Kingdom of Saudi Arabia with 283 deaths. ==Taxonomy==