ABSTRACT
AO_SCPLOWBSTRACTC_SCPLOWPersistent SARS-CoV-2 infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. It has been speculated that the emergence of antigenically diverse SARS-CoV-2 variants such as the Omicron variant may be the result of intra-host viral evolution driven by suboptimal immune responses, which must be followed by forward transmission. However, while intrahost evolution has been documented, to our knowledge no direct evidence of subsequent forward transmission is available to date. Here we describe the emergence of an Omicron BA.1 sub-lineage with 8 additional amino acid substitutions within the spike (E96D, L167T, R346T, L455W, K458M, A484V, H681R, A688V) in an immune-compromised host along with evidence of 5 forward transmission cases. Our findings show that the Omicron BA.1 lineage can further diverge from its exceptionally mutated genome during prolonged SARS-CoV-2 infection; highlighting an urgent need to employ therapeutic strategies to limit duration of infection and spread in vulnerable patients.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
The COVID-19 pandemic sparked rapid development of SARS-CoV-2 diagnostics. However, emerging variants pose the risk for target dropout and false-negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY(R) SARS-CoV-2 Panel combines RT-PCR and MALDI-TOF mass-spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified dataset of 1,262 SARS-CoV-2-positive specimens from Mount Sinai Health System (New York City) from December 2020 through April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly-specific for the alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS-CoV-2 variants.
Subject(s)
COVID-19ABSTRACT
New York City (NYC) emerged as a coronavirus disease 2019 (COVID-19) epicenter in March 2020, but there is limited information regarding potentially unrecognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first reported case. We utilized a sample pooling strategy to screen for SARS-CoV-2 RNA in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across our NYC health system who were evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We obtained complete SARS-CoV-2 genome sequences from samples collected between late February and early March. Additionally, we detected SARS-CoV-2 RNA in pooled specimens collected in the week ending 25 January 2020, indicating that SARS-CoV-2 caused sporadic infections in NYC a full month before the first officially documented case.
Subject(s)
COVID-19 , Coronavirus Infections , Signs and Symptoms, RespiratoryABSTRACT
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.