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Commentary
Media Myth On
Beta Coronavirus Source
Recombinomics
Commentary 18:00
February 12, 2013
The above comments reiterate the position that the recent human beta cornavirus infections are linked to animal exposure, either directly or through an environmental source such as contaminated water or fruit. However, there is limited support for a recent transmission linked to an animal reservoir such as bats, the most frequently cited reservoir for coronavirus.
The linkage with bats stems from extensive surveys that were initially linked to to SARS-CoV outbreak that began in late 2002 and spread internationally in early 2003. At the time, cornaviruses had been isolated from human and poultry, and the known examples fell into three distinct groups. Group 1, also designated as alpha coronavirus was represent by a human cold virus,229E. Group 2 (beta coronaviruses) was represented by another human cold virus, OC43. Group 3 (gamma coronaviruses) was represented by a poulty virus, infectious bronchitis virus (IBV).
Although the SARS CoV was a Group 2 virus, it was easily distinguished from OC43, and therefore classified as novel. Closely related sequences were found in multiple species sold in live markets in Hong Kong (most notably the Himalaya palm civet), but all of the animal sequences were closed related to each other, as well as the human isolates, raising the possibility that the animal isolates were due to recent infections in the live markets due to animal to animal transmission or human to animal transmission. This possibility was supported by the failure to find the SARS CoV in the animal species in the wild.
An extensive survey of wild animals led to the identification of multiple versions of coronaviruses in bats, including a SARS CoV that had 98% identity with the human cases. Thus, bats were considered the natural reservoir for SARS CoV. The extensive survey of bats led to the identification of additional coronavirus, including subgroups among the beta coronavirus. OC43 was designated as group 2a and SARS CoV was group 2b, while additional isolates from bats were designated as group 2c and 2d.
When a novel coronavirus was isolated from a fatal case (60M) in Saudi Arabia, it was also novel and most closely related to the bat group 2c viruses from Guangdong province (HKU-4 and HKU-5), such as Bat coronavirus HKU4-1 and Bat coronavirus HKU5-2. Full sequences were public and the relatedness with the human sequences (Human betacoronavirus 2c EMC/2012 or Betacoronavirus England 1) was approximately 70%. A segment from a 2c bat sequence from the Netherlands, Bat coronavirus BtCoV/UKR-G17/Pip_nat/UKR/2011, had 91% identity, but the sequence was from a highly conserved region. A recent bat survey for additional group 2c sequences led to the identification of 3 sets from Africa (Ghana) and 3 sets from Europe (Romania and Ukraine). The three sequences from Ghana were Betacoronavirus BtCoV/KW2E-F53/Nyc_spec/GHA/2011, Betacoronavirus BtCoV/KW2E-F93/Nyc_spec/GHA/2010, and Betacoronavirus BtCoV/KW2E-F82/Nyc_spec/GHA/2011 The most closely related sequences were from Ukraine (Bat coronavirus BtCoV/UKR-G17/Pip_nat/UKR/2011) and Romania (Bat coronavirus BtCoV/8-691/Pip_nat/ROU/2009 and Bat coronavirus BtCoV/8-724/Pip_pyg/ROU/2009) with 88% identity to the novel human sequences, which was greater than the 70% in sequences from Guangdong province, but well shy of the 98% seen when human SARS CoV was compared to bat SARS CoV.
In contrast, all of the human sequences have been at least 99.5% identical which each other, including full sequences from the first two confirmed cases (from Saudi Arabia and Qatar) or partial sequences from subsequent sequences from cases in Saudi Arabia and Qatar. Moreover, it is likely that the two sets of sequences from the cases in Jordan, as well as the cluster in Saudi Arabia and the most recent cases, who was a UK resident who traveled to Pakistan and Saudi Arabia, where he (60M) developed symptoms, are also 99.5% identical to the public sequences based on detection by probes made from the two sets of full sequences.
Thus, the sequence data does not support a recent jump from bats to humans, which is also true for camels.
Moreover, the failure to detect the virus in symptomatic contacts, raises serious concerns regarding the sensitivity of the assay. WHO has classified these contacts as probable cases, signaling the lack in confidence in the assay. In addition, WHO has suggested that the viral level may be higher in the lower respiratory tract, again raising serious questions about the ability to detect the coronavirus using protocols involving nasopharyngeal swabs from the upper respiratory tract.
In spite of these limitations, ECDC suggests that they failure to identify mild cases suggest the virus transmission is linked to an animal or environment source.
The discovery of H1N1psm09 in the most recent case raises additional concerns that co-infected cases will be diagnosed as H1N1pdm09 cases, since the symptoms linked to each virus are similar.
The H1N1pdm09 may also facilitate transmission, raising further concerns that the novel coronavirus is far more common in humans than indicated by the limited number of lab confirmed cases.
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