Intermediate A-B SARS-CoV-2 genomes existed among early human cases
2 events · 1 assessment
Assessed Contested
verdict confidence 0.80
Whether genuine intermediate genomes — carrying one but not both of the two nucleotide substitutions that distinguish SARS-CoV-2 lineages A and B — circulated among early human COVID-19 cases is an open and consequential question in the debate over the pandemic's origin. It matters because the two-spillover hypothesis (Pekar et al., 2022) holds that lineages A and B entered humans in separate zoonotic events, with the single-mutation intermediate linking them existing only in an unsampled animal host; a confirmed intermediate genome in an early human case would undercut that inference and make a single introduction followed by in-human diversification more plausible. Roughly twenty human-derived sequences with intermediate haplotypes have been reported in sequence databases, so the disagreement is not about whether such sequences were recorded but about what they represent. Critics (Kumar, Pipes, Nei and colleagues) argue the sequences are authentic and were improperly excluded from the phylodynamic analysis; Pekar, Wertheim, Worobey and colleagues argue they are contamination or bioinformatic artifacts, or arose by convergent mutation and reversion rather than being true ancestral intermediates. No reported intermediate has yet been established to the wider field's satisfaction as a genuine early-human biological intermediate, and the question turns almost entirely on the authenticity and correct interpretation of those specific sequences — precisely where the credible literature remains divided. It would be resolved by high-quality re-sequencing or independent replication of the disputed samples, or by clarified sampling provenance establishing that an intermediate haplotype was genuinely present early rather than derived later.
Claim entered the graph