Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat

Abstract

The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.

Shared within-host SARS-CoV-2 variation in households

“…As previously reported[9,33,34], iSNVs are not consistently recovered within serial samples. Among individuals with recovered within-host diversity, a mean of 8.7% within-host iSNVs above a minor allele frequency of 1.0% and applying all filters were recovered one day later; this proportion declined with time between samples, though not significantly (r = -0.11, p = 0.23).…”

“…As others have reported [9,23,33,34], excluding sources of noise from within-host pathogen genomic data remains a major challenge. We sequenced artificial strain mixtures of two SARS-CoV-2 variants of concern and found significant tradeoffs between sensitivity and specificity in recovery of true within-host variants as increasingly strict variant filters were applied.…”

The Evolution and Biology of SARS-CoV-2 Variants

“…The main driver of virus evolution (i.e., reproductive success in terms of onward transmissions) is an interplay of chance epidemiological effects, mutations that impact immune escape, and adaptation to the new host, all occurring in a changing host landscape marked by past exposures, vaccinations, and boosters. An additional wildcard is that viral evolution involves occasional fixation of low-frequency mutations during transmission (i.e., there are strong transmission bottlenecks that dominate viral evolution even during superspreading events) (Hannon et al 2022). SARS-CoV-2 has repeatedly acquired enhanced transmissibility and immuneevasion properties to enable it to persist in this changing landscape.…”