Owen, C. J. | Search bioRxiv

bioRxiv2020

No detectable signal for ongoing genetic recombination in SARS-CoV-2

The COVID-19 pandemic has led to an unprecedented global sequencing effort of its viral agent SARS-CoV-2. The first whole genome assembly of SARS-CoV-2 was published on January 5 2020. Since then, over 150,000 high-quality SARS-CoV-2 genomes have been made available. This large genomic resource has allowed tracing of the emergence and spread of mutations and phylogenetic reconstruction of SARS-CoV-2 lineages in near real time. Though, whether SARS-CoV-2 undergoes genetic recombination has been largely overlooked to date. Recombination-mediated rearrangement of variants that arose independently can be of major evolutionary importance. Moreover, the absence of recombination is a key assumption behind the application of phylogenetic inference methods. Here, we analyse the extant genomic diversity of SARS-CoV-2 and show that, to date, there is no detectable hallmark of recombination. We assess our detection power using simulations and validate our method on the related MERS-CoV for which we report evidence for widespread genetic recombination.

genomics↗

bioRxiv2020

Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses

Several studies have reported the presence of pre-existing humoral or cell-mediated cross-reactivity to SARS-CoV-2 peptides in healthy individuals unexposed to SARS-CoV-2. In particular, the current literature suggests that this pre-existing cross-reactivity could, in part, derive from prior exposure to common cold endemic human coronaviruses (HCoVs). In this study, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the entire diversity of the Coronaviridae family. Slightly over half (54.8%) of the tested epitopes did not have noticeable homology to any of the human endemic coronaviruses (HKU1, OC43, NL63 and 229E), suggesting prior exposure to these viruses cannot explain the full cross-reactive profiles observed in healthy unexposed individuals. Further, we find that the proportion of cross-reactive SARS-CoV-2 epitopes with noticeable sequence homology is extremely well predicted by the phylogenetic distance to SARS-CoV-2 (R2 = 96.6%). None of the coronaviruses sequenced to date showed a statistically significant excess of T-cell epitope homology relative to the proportion of expected random matches given the sequence similarity of their core genome to SARS-CoV-2. Taken together, our results suggest that the repertoire of cross-reactive epitopes reported in healthy adults cannot be primarily explained by prior exposure to any coronavirus known to date, or any related yet-uncharacterised coronavirus.

immunology↗