The WHO’s Global Study on the Origins of SARS-CoV-2

By Isabelle Ferenczi

The World Health Organization (WHO) released a joint study, (WHO Headquarters, 2021), conducted between 4 January 2021 and 10 February 2021 in partnership with the World Organisation for Animal Health, the Food and Agriculture Organization of the United Nations, and a team of multidisciplinary Chinese experts. This study aimed to identify the source and introduction route of the SARS-CoV-2 virus into the human population. The study focussed on three main components: epidemiology, molecular epidemiology and bioinformatics, and animals and the environment.

Epidemiology

Based on sentinel surveillance data, there was an increase in Influenza-Like Illness (ILI) cases in Wuhan in December 2019, but without any evidence of SARS-Cov-2 transmission. Similarly, sentinel surveillance data for severe acute respiratory illness (SARI) suggested there was no increase in SARI cases in late 2019, although this could be due to “lack of sensitivity or data incompleteness” as well as limited information. Nucleic acid testing of samples from patients with ILI or SARI in late 2019 was found to be negative for SARS-CoV-2. However, by early January 2020, nucleic acid testing found that 9 out of 45 patients with ILI were positive for SARS-CoV-2.

Later in the third week of 2020, there was an increase in all-time mortality.  Virus transmission is likely to have been widespread in Wuhan by 1-7 January 2020, as the median time lag between disease onset and death is 17 days. This increase was mirrored in Hubei Province (the population outside Wuhan) after a 1–2-week delay, thus suggesting that transmission originally began in Wuhan. Though many disease cases were associated with the Huanan Seafood Market in Wuhan, earlier unassociated cases were identified too. Therefore, either Huanan Market was not the source, or unidentifiable asymptomatic cases link the early cases to the market. As of yet, no conclusion has been reached on the role of the market or the route of infection into the market.

Molecular epidemiology

Genomic data from Animal viruses found coronaviruses that are phylogenetically related to SARS-CoV-2 in bats and customs-seized trafficked Malayan pangolins, as shown in Figure 1. These coronaviruses are not similar enough to be the direct progenitors of SARS-CoV-2, however, they could be reservoirs of the virus.

Figure 1: A phylogenetic tree showing SARS-CoV-2 and other coronaviruses which are found in bats and pangolins.

Also, minks and cats have a high susceptibility to SARS-CoV-2 and thus these animals could be potential reservoirs. Based on molecular sequence data, it was concluded that the outbreak first began in the months before December 2019. Studies in other countries discovered that early samples of the virus were detected there prior to detection in Wuhan. For example, sewage samples in Barcelona, Spain, were found to be positive for SARS-CoV-2 RNA on 12 March 2019, however, this could be a false result. Similarly, Codogno, Italy, had positive sewage samples in mid-December 2019 and Brazil in November 2019. Similarly, serological studies in France (mid-December) and the USA (17December 2019 – 17 January 2020) also suggested that transmission was widespread earlier than previously thought.

Animal and environmental studies

Over 1000 bats from the Hubei area were sampled and yet none carried viruses similar to SARS-CoV-2. 80,000 wildlife, livestock, and poultry samples were collected from across China, however, no SARS-CoV-2 antibodies or nucleic acids were found before or after the outbreak. Frozen produce sold in Huanan Market was also tested, but all samples tested negative for the SARS-CoV-2 nucleic acid. Meanwhile, cold produce was not tested as its importance was not sufficiently appreciated at the time, although suppliers had come from countries where SARS-CoV-2 was found prior to the outbreak. Testing at other markets in Wuhan and upstream suppliers found no SARS-CoV-2 circulating in animals. Nonetheless, samples taken from surfaces of the Huanan Market found that there was widespread contamination of the virus.

Overall, the researchers concluded that there are four potential scenarios for introduction into the human population, as depicted in Figure 2, and determined the likelihood of each scenario.

Figure 2: Diagram representing the four possible pathways of SARS-CoV-2 emergence. It was determined to be “extremely unlikely” that the virus was introduced via a laboratory incident. On the other hand, introduction through the cold/food chain was considered “possible” and direct zoonotic spill-over was considered “likely”. Introduction through intermediate host followed by zoonotic transmission was considered to be “very likely”.

Conclusion

In conclusion, based on surveillance data, there was no clear indication of substantial SARS-CoV-2 circulation in late 2019 in Wuhan. Yet, molecular sequence data showed that the outbreak first began in the months before December 2019. Besides, studies in other countries (Spain, Italy, Brazil, France, USA) found that early samples of the virus were detected there prior to detection in Wuhan. Bats, pangolins, and highly susceptible animals could be reservoirs for SARS-CoV-2. The most likely SARS-CoV-2 introduction route was determined to be via an intermediate animal host followed by spill-over into humans as well as other routes of viral introduction.

This study is crucial to better understand zoonotic sources of infection, intermediate hosts, and routes of introduction. To reduce the risk of future zoonoses, further studies remain necessary to elucidate the route of SARS-CoV-2.

Bibliography

WHO Headquarters, 2021. WHO-convened global study of origins of SARS-CoV-2: China Part. [online] Available at: <https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part&gt; [Accessed 6 April 2021].

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