Bats Invented COVID

COVID's two original strains, A and B migrated from a particular species of bats to humans in China, in at least two separate incidents, no earlier than November of 2019. Samples from humans near the Hunan market were found by December of that year.

Understanding the circumstances that lead to pandemics is critical to their prevention. Here, we analyze the pattern and origin of genomic diversity of SARS-CoV-2 early in the COVID-19 pandemic. We show that the SARS-CoV-2 genomic diversity prior to February 2020 comprised only two distinct viral lineages—denoted A and B—with no transitional haplotypes. Novel phylodynamic rooting methods, coupled with epidemic simulations, indicate that these two lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses and occurred in late-November/early-December 2019 and no earlier than the beginning of November 2019, while the introduction of lineage A likely occurred within weeks of the first event. These findings define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. Hence, as with SARS-CoV-1 in 2002 and 2003, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

Pekar, et al., "SARS-CoV-2 emergence very likely resulted from at least two zoonotic events" (February 26, 2022).

The introduction to the paper explains:

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for the coronavirus disease 19 (COVID-19) pandemic that has caused more than 5 million confirmed deaths in the two years since its detection at the Huanan Seafood Wholesale Market (hereafter the ‘Huanan market’) in December 2019 in Wuhan, China. 

As the original outbreak spread to other countries, the diversity of SARS-CoV-2 quickly increased and led to the emergence and identification of multiple variants of concern, but the beginning of the pandemic was marked by two major lineages denoted ‘A’ and ‘B’. 

Lineage B has been the most common throughout the pandemic and includes all sequenced genomes from humans directly associated with the Huanan market, including the earliest sampled genome, Wuhan/IPBCAMS-WH-01/2019, and the reference genome, Wuhan/Hu-1/2019 (hereafter ‘Hu-1’), sampled on 24 and 26 December 2019, respectively. All published sequences from environmental samples taken at Huanan Market also fall in lineage B. 

The earliest lineage A viruses, Wuhan/IME-WH01/2019 and Wuhan/WH04/2020, were sampled on 30 December 2019 and 5 January 2020, respectively, and they differ from lineage B by two nucleotide substitutions: C8782T and T28144C. Notably, the nucleotides at these two positions in lineage A are identical to related viruses of Rhinolophus bats, which are presumed to represent the ultimate host reservoir. . . . 

The earliest lineage A genomes lack a direct epidemiological connection to the Huanan market, but, importantly, were sampled from individuals who lived or had recently stayed close to the market. 

Despite the availability of these data, three central questions remain: if lineage B viruses are more distantly related to sarbecoviruses from Rhinolophus bats, (i) why were they detected earlier than lineage A viruses, (ii) why were only lineage B viruses found in humans at the Huanan market, and (iii) why did lineage B predominate early in the pandemic? 

Paramount to answering these questions is determining the ancestral haplotype: the genomic sequence characteristics of the most recent common ancestor (MRCA) at the root of the SARS-CoV-2 phylogeny. Although the root has often been inferred with Bayesian and maximum likelihood methods to fall on the branch leading to IPBCAMS-WH-01 (Lineage B) or other early genomes, reanalysis of sequence data from the earliest sampled viruses found that three previously reported mutations in IPBCAMS-WH-01 were spurious, and the genome was, in fact, identical to the Hu-1 reference genome. Other early genomes were also found to have spurious mutations, thereby decreasing the overall genetic diversity of early SARS-CoV-2 sequence data. This decreased diversity suggests that prior studies, including our own, may have incorrectly rooted the SARS-CoV-2 phylogeny. 

Alternatively, it has been suggested that multiple SARS-CoV-2 introductions from an intermediate host led to separate origins of lineages A and B and that the MRCA of SARS-CoV-2 existed in an animal reservoir, rather than in humans. 

In this study, we analyze the evolutionary and epidemiological dynamics at the start of the COVID-19 pandemic. By combining genomic and epidemiological data, novel phylodynamic models, and epidemic simulations, we eliminate many of the haplotypes previously suggested as the MRCA of SARS-CoV-2 and show that the pandemic most likely began with at least two separate zoonotic transmissions starting no earlier than November 2019, with a lineage A virus jumping into humans after the introduction of a lineage B virus.