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The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 - PubMed

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Jonathan E Pekar et al. Science. .

Erratum in

Abstract

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

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Figures

Fig. 1.
Fig. 1.. Maximum likelihood phylogeny of the early SARS-CoV-2 pandemic, showing nucleotide reversions and putative candidates for the ancestral haplotype at the most common recent ancestor (MRCA).

Putative ancestral haplotypes are identified with colored shapes. Reversions from the Hu-1 reference genotype to the recCA are colored. Blue represents C-to-T reversions and black indicates all other reversions. The tree is rooted on Hu-1 to show reversion dynamics to the recCA.

Fig. 2.
Fig. 2.. Probability of phylogenetic structures arising from a single introduction of SARS-CoV-2 in epidemic simulations.

(A) A large polytomy of at least 20 descendent lineages, consistent with the base of both lineages A and B. (B) Topology matching a C/C ancestral haplotype: two clades each one mutation from the ancestor, both with polytomies of at least 20 descendent lineages. (C) Topology matching either a lineage A or lineage B ancestral haplotype: a basal polytomy with at least 20 descendent lineages including a large clade separated by two mutations, also possessing a polytomy of at least 20 descendent lineages. Basal taxa have short branch lengths for clarity. The probability of each phylogenetic structure after a single introduction is reported in the box.

Fig. 3.
Fig. 3.. Comparison of the tMRCA and primary case dates for lineage A and lineage B across rooting strategies.

Each row represents a different rooting constraint in phylodynamic analysis, with lineage B, C/C and lineage A representing a fixed ancestral haplotype. (A) The tMRCA for lineages A and B. (B) The number of weeks the tMRCA of lineage A occurs after the tMRCA of lineage B. (C) The timing of the primary case for lineages A and B. (D) The number of weeks the time of the primary case of lineage A occurs after the time of the primary case of lineage B. Long dashed lines indicate the median and shading represents the 95% HPD for each distribution. Short dashed lines indicate 0 weeks difference between lineages A and B. Posterior probability that lineage A originated after lineage B is reported in the grey box.

Fig. 4.
Fig. 4.. Dynamics of simulated SARS-CoV-2 epidemics resulting from separate introductions of lineages A and B.

Each row represents a different rooting constraint in phylodynamic analysis, with lineage B, C/C and lineage A representing a fixed ancestral haplotype. (A) Estimated number of infections. The header of each column indicates whether the number of infections are caused by lineage A, lineage B, or the two lineages combined. Darker and lighter shading represent the 50% and 95% HPD, respectively. (B) The log ratio of lineage B to lineage A infections on 15 December 2019. Posterior probability of having more lineage B infections than lineage A reported in the grey box.

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