AO_SCPLOWBSTRACTC_SCPLOWPersistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, to our knowledge, no direct evidence of subsequent transmission and stepwise adaptation is available. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome during persistent infection in more than one host, and also document ongoing transmission of these novel variants. There is an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City. MethodsIndividuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies. ResultsAll but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution. ConclusionsHere we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus.
New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV2 pandemic. To identify the early events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
