Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization

Abstract

Background The variant of concern, Omicron, has become the sole circulating SARS-CoV-2 variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021- January 2022. In this study, we compare the clinical outcomes in patients infected with different Omicron subvariants and compare the relative viral loads, and recovery of infectious virus from upper respiratory specimens. Methods SARS-CoV-2 positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared to infections with BA.1. Cycle threshold values (Ct) and the recovery of infectious virus on VeroTMPRSS2 cell line from clinical specimens were compared. Results The BA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and COVID-19 related hospitalizations at the Johns Hopkins system. After a peak in January, cases fell in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct when compared to other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values less than 20. Conclusions Omicron subvariants continue to be associated with a relatively high rate of PCR positivity and hospital admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves.

Reduced control of SARS-CoV-2 infection is associated with lower mucosal antibody responses in pregnant women

“…Base-calling of reads was conducted using the MinKNOW, followed by demultiplexing with guppybarcoder that requires barcodes at both ends. Artic-ncov2019 medaka protocol was used for alignment and variant calling [17, 18]. Clades were determined using Nextclade beta v 1.13.2 (clades.nextstrain.org, Last accessed March 30, 2022), and lineages were determined with Pangolin COVID-19 lineage Assigner [19].…”

“…TMPRSS2 VeroE6 cells (RRID: CVCL_YQ49) obtained from the cell repository of the National Institute of Infectious Diseases, Japan [18, 21], and were cultured as previously described [22]. For virus isolation, cells plated in 24-well dishes had the culture media replaced with 350 µL of infection media (culture media except that the FBS was reduced to 2.5%), followed by the addition of 150 µL of swab specimen.…”

SARS‐CoV‐2 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan‐coronavirus fusion inhibitors

“…Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have continuously emerged and caused several epidemic-like waves of Omicron. 1 The most dominant Omicron subvariants were originated from BA.2, BA.4, or BA.5 sublineages, such as BA.2.12.1, BA.2.75, BA.4.6, BA.5.2, and BF.7. [2][3][4][5] Particularly, the newly emerged XBB and XBB.1.5 subvariants, 6,7 are derived from the BA.2 sublineage (www.gisaid.org), however, it harbors a distinct mutant profile in its spike (S) protein.…”

“…Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron subvariants have continuously emerged and caused several epidemic‐like waves of Omicron 1 . The most dominant Omicron subvariants were originated from BA.2, BA.4, or BA.5 sublineages, such as BA.2.12.1, BA.2.75, BA.4.6, BA.5.2, and BF.7 2–5 .…”

Impact of SARS-CoV-2 envelope protein mutations on the pathogenicity of Omicron XBB

“…In comparison with the original strain and other variants, the pathogenicity of Omicron variants was milder 2 . However, it is worth noting that BA.5 infection has shown an increased rate of recovery positivity and an increased proportion of infections that were “symptomatic” 3 . These phenomena remind us to be alert to the change in pathogenicity.…”