Global cold-chain related SARS-CoV-2 transmission identified by pandemic-scale phylogenomics.

DEAR EDITOR, The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a tremendous threat to human society.SARS-CoV-2 is airborne and transmits primarily through social contact;however,whether cold chain-related transmission has occurred remains highly debated(Han&Liu,2022;Lewis,2021;Ma et al.,2021;Mallapaty et al.,2021;Pang et al.,2020;Wu et al.,2021).Here,we present a novel method and identify two transmission routes based on lineage-specific reductions in the SARS-CoV-2 evolutionary rate.After analyzing 4 039 521 SARS-CoV-2 genomic sequences,we identified two outbreaks in Xinfadi-Beijing and Auckland that may be cold-chain related,caused by two mutation-dormant variants,respectively.A mutation-dormant variant represents a variant with a(nearly)identical genomic sequence repeatedly isolated over a long period of time.Dalian outbreak in July 2020 and Yingkou outbreak ten months later were epidemiologically connected and derived from a mutation-dormant variant.Furthermore,the earliest SARS-CoV-2 variant(i.e.,the most recent common ancestor of SARS-CoV-2)was also found to be a mutation-dormant variant.Its spillover events were repeatedly observed during the last two years,indicating that the COVID-19 outbreak in Wuhan may be associated with spillover events from cold-chains.In all observed cases,the virus re-started mutating after spillover events from cold-chains.Systematic identification of spillover events revealed that the frequency of cold-chain related transmission is in the order of 0.1％-10％.Our results indicate that that cold-chain related transmission is rare but may have occurred globally.