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In a recent study published in Science, the researchers demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) zoonotic spillover to humans involved two separate cross-species transmission events, and lineages A and B viruses.

Background

It is crucial to understand the circumstances which lead to a pandemic to prevent future pandemics. In the case of the coronavirus disease 2019 (COVID-19) pandemic, which began in late 2019 in the Huanan market of Wuhan, China, the diversity of SARS-CoV-2 quickly increased, leading to the emergence of multiple variants of concern (VOCs). However, dr rama pediatric pulmonary medicine its initial phase was marked by only two major 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 remained the most common throughout the pandemic. Later, two samples collected on 30 December 2019 and 5 January 2020 from Wuhan showed the presence of lineage A 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 instance, 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 the genomic characteristics of the most recent common ancestor (MRCA) of SARS-CoV-2 to help understand the evolution of lineages A and B.

They deployed phylodynamic rooting methods combined with epidemic simulations to study SARS-CoV-2 genomic diversity before February 2020. The researchers reconstructed the genome of a hypothetical progenitor of SARS-CoV-2 to study its mutational pattern. Further, they used a random-effects substitution model to infer the ancestral SARS-CoV-2 haplotype. Finally, the researchers inferred the time of the lineage B and lineage A primary cases, accounting for the symptom onset date and earliest documented COVID-19 hospitalization date.

Study findings

By February 14, 2020, the researchers identified 787 near-full length genomes from SARS-CoV-2 lineages A and B. Due to convergent evolution, the authors continually observed C/C and T/T genomes throughout the pandemic. The genome of the recombinant common ancestor (“recCA”) differed from Hu-1 by just 381 substitutions, including C8782T and T28144C. This finding indicated that genetic similarity to related viruses was a poor substitute for the ancestral haplotype. The authors observed 23 unique reversions and 631 unique substitutions across the SARS-CoV-2 phylogeny by February 2020.

The authors also successfully inferred the ancestral haplotype of the 787 lineage A and B genomes sampled by 14 February 2020. Phylodynamic rooting favored a lineage B or C/C ancestral haplotype, although lineage B exhibited more divergence from the root of the SARS-CoV-2 phylogeny tree than expected. Further, it showed that a lineage A ancestral haplotype was inconsistent with the molecular clock, with Bayes factor (BF) = 48.1. Due to the C-to-T transition bias, the T/T ancestral haplotype, with BF>10 was also disfavored. Epidemic simulations did not support the notion that a single introduction of SARS-CoV-2 gave rise to the observed phylogeny.

The researchers could infer only three possible ancestral haplotypes -lineage A, lineage B, and C/C. Further, they inferred the time of most recent common ancestor (tMRCA) for SARS-CoV-2 to be 11 December 2019 which remained consistent in the recCA-rooted and fixed ancestral haplotype studies. The genomes sequenced early during the pandemic had 35.2% and 64.8% of lineages A and B, respectively. Moreover, they had a large polytomy, which refers to the descending of multiple lineages from a single node on the phylogenetic tree. The infection dates of the lineage B and lineage A primary cases were 18 and 25 November 2019, respectively. In 64.6% of the posterior samples, the lineage B cases predated lineage A cases by an average of seven days.

Conclusions

The study results defined a narrow window during which SARS-CoV-2 first spilled over 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 18 November 2019 and involved lineage B viruses, while the second occurred within weeks of the first event and involved lineage A viruses. Additional, cryptic introductions also likely accompanied these two zoonotic events, and the authors also raised the possibility of failed introductions of intermediate SARS-CoV-2 haplotypes.

Multiple studies have demonstrated 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 within humans to spread.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.