In a recent study published in Science, researchers showed that the zoonotic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans involved two transmission events between different species and the viruses of the lineages A and B.
Study: Molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Image credit: Crystal Eye Studio/Shutterstock
background
Understanding the circumstances that lead to a pandemic is crucial to preventing future pandemics. In the case of the coronavirus disease 2019 (COVID-19) pandemic, which began in late 2019 in Huanan Market in Wuhan, China, the diversity of SARS-CoV-2 increased rapidly, leading to the appearance of multiple variants of concern (VOC). However, its initial phase was marked by only two main lineages, ‘A’ and ‘B’.
The reference genome, Wuhan/Hu-1/2019, and the earliest genome, Wuhan/IPBCAMS-WH-01/2019, sampled on 24 and 26 December 2019, respectively, belonged to lineage B, which was remain the most common throughout the pandemic. . Later, two samples collected on December 30, 2019 and January 5, 2020 in Wuhan showed the presence of A lineage viruses.
While SARS-CoV-2 lineage B has a “C/T” pattern at nucleotide positions, C8782, T28144, lineage A viruses have a “T/C” pattern at nucleotide positions, C8782T, T28144C. Studies have not answered several questions about the evolution of these two SARS-CoV-2 lineages. For example, why did lineage B predominate in the early pandemic phase despite being distantly related to sarbecoviruses from Rhinolophus bats, the presumed host reservoir of SARS-CoV-2?
About the study
In the present study, researchers gathered genomic and epidemiological data from the early phase of the COVID-19 pandemic to determine the ancestral haplotype and genomic characteristics of the most recent common ancestor (MRCA) of SARS-CoV-2 by help understand evolution. of lineages A and B.
They deployed phylodynamic rooting methods combined with epidemic simulations to study the genomic diversity of SARS-CoV-2 before February 2020. The researchers reconstructed the genome of a hypothetical progenitor of SARS-CoV-2 to study the its mutational pattern. In addition, they used a random-effects substitution model to infer the ancestral SARS-CoV-2 haplotype. Finally, the researchers inferred the time of the primary B-lineage and A-lineage cases, taking into account the date of onset of symptoms and the earliest documented date of hospitalization for COVID-19.
Results of the study
On February 14, 2020, researchers identified 787 near-full-length genomes from SARS-CoV-2 lineages A and B. Because of convergent evolution, the authors continuously observed C/C and T/T genomes throughout the pandemic. The genome of the recombinant common ancestor (“recCA”) differed from Hu-1 by only 381 substitutions, including C8782T and T28144C. This finding indicated that genetic similarity to related viruses was a poor proxy for the ancestral haplotype. The authors observed 23 unique reversions and 631 unique substitutions across the SARS-CoV-2 phylogeny as of February 2020.
The authors also successfully inferred the ancestral haplotype of the 787 A and B lineage genomes sampled on February 14, 2020. Phylodynamic rooting favored an ancestral B or C/C lineage haplotype, although the B lineage showed more divergence from the root of the SARS-CoV-2 phylogeny tree than expected. Furthermore, it showed that an ancestral haplotype of lineage A was inconsistent with the molecular clock, with Bayes factor (BF) = 48.1. Due to the CaT transition bias, the ancestral T/T haplotype, with BF>10, was also disfavored. Epidemic simulations did not support the idea that a single introduction of SARS-CoV-2 gave rise to the observed phylogeny.
Researchers could only infer three possible ancestral haplotypes: lineage A, lineage B, and C/C. They further inferred the time of the most recent common ancestor (tMRCA) of SARS-CoV-2 to be 11 December 2019, which remained consistent across studies of rooted and fixed ancestral haplotypes in recCA. Genomes sequenced early in the pandemic had 35.2% and 64.8% of the A and B lineages, respectively. In addition, they had high polytomy, which refers to the descent of multiple lineages from a single node of the phylogenetic tree. The dates of infection for the primary cases of lineage B and lineage A were November 18 and 25, 2019, respectively. In 64.6% of subsequent samples, lineage B cases preceded lineage A cases by an average of seven days.
Conclusions
The study results defined a narrow window during which SARS-CoV-2 first spilled into humans to cause the first cases of COVID-19. Interestingly, it involved two independent zoonotic events, with lineage A and B progenitor viruses co-circulating in non-human mammals before their spillover into humans. The first event occurred around November 18, 2019 and involved lineage B viruses, while the second occurred a few weeks after the first event and involved lineage A viruses. Additional and critical introductions also accompany these two zoonotic events, and the authors also raised the possibility of failed introductions of intermediate SARS-CoV-2 haplotypes.
Several studies have shown that SARS-CoV-2 has the potential to reverse zoonosis in Syrian hamsters and white-tailed deer. Overall, these findings suggest that SARS-CoV-2 did not have to adapt to humans to spread.