Comparative hospitalization risk for SARS-CoV-2 Omicron and Delta variant infections, by variant predominance periods and patient-level sequencing results, New York City, August 2021-January 2022.

BACKGROUND: Comparing disease severity between SARS-CoV-2 variants among populations with varied vaccination and infection histories can help characterize emerging variants and support healthcare system preparedness. METHODS: We compared COVID-19 hospitalization risk among New York City residents with positive laboratory-based SARS-CoV-2 tests when ≥98% of sequencing results were Delta (August-November 2021) or Omicron (BA.1 and sublineages, January 2022). A secondary analysis defined variant exposure using patient-level sequencing results during July 2021-January 2022, comprising 1-18% of weekly confirmed cases. RESULTS: Hospitalization risk was lower among patients testing positive when Omicron (16,025/488,053, 3.3%) than when Delta predominated (8268/158,799, 5.2%). In multivariable analysis adjusting for demographic characteristics and prior diagnosis and vaccination status, patients testing positive when Omicron predominated, compared with Delta, had 0.72 (95% CI: 0.63, 0.82) times the hospitalization risk. In a secondary analysis of patients with sequencing results, hospitalization risk was similar among patients infected with Omicron (2042/29,866, 6.8%), compared with Delta (1780/25,272, 7.0%), and higher among the subset who received two mRNA vaccine doses (adjusted relative risk 1.64; 95% CI: 1.44, 1.87). CONCLUSIONS: Hospitalization risk was lower among patients testing positive when Omicron predominated, compared with Delta. This finding persisted after adjusting for prior diagnosis and vaccination status, suggesting intrinsic virologic properties, not population-based immunity, explained the lower severity. Secondary analyses demonstrated collider bias from the sequencing sampling frame changing over time in ways associated with disease severity. Representative data collection is necessary to avoid bias when comparing disease severity between previously dominant and newly emerging variants.

Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New York City.

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.

Rapid Emergence and Epidemiologic Characteristics of the SARS-CoV-2 B.1.526 Variant - New York City, New York, January 1-April 5, 2021.

Recent studies have documented the emergence and rapid growth of B.1.526, a novel variant of interest (VOI) of SARS-CoV-2, the virus that causes COVID-19, in the New York City (NYC) area after its identification in NYC in November 2020 (1-3). Two predominant subclades within the B.1.526 lineage have been identified, one containing the E484K mutation in the receptor-binding domain (1,2), which attenuates in vitro neutralization by multiple SARS-CoV-2 antibodies and is present in variants of concern (VOCs) first identified in South Africa (B.1.351) (4) and Brazil (P.1).* The NYC Department of Health and Mental Hygiene (DOHMH) analyzed laboratory and epidemiologic data to characterize cases of B.1.526 infection, including illness severity, transmission to close contacts, rates of possible reinfection, and laboratory-diagnosed breakthrough infections among vaccinated persons. Preliminary data suggest that the B.1.526 variant does not lead to more severe disease and is not associated with increased risk for infection after vaccination (breakthrough infection) or reinfection. Because relatively few specimens were sequenced over the study period, the statistical power might have been insufficient to detect modest differences in rates of uncommon outcomes such as breakthrough infection or reinfection. Collection of timely viral genomic data for a larger proportion of citywide cases and rapid integration with population-based surveillance data would enable improved understanding of the impact of emerging SARS-CoV-2 variants and specific mutations to help guide public health intervention efforts.