In a recent study posted to the medRxiv* preprint server, researchers compare the clinical outcomes, upper respiratory viral loads, and viral recovery of various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants on cell cultures.

Study: Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization. Image Credit: Mayboon/Shutterstock

Background

For the reason that SARS-CoV-2 Omicron variant emerged in November 2021, various Omicron subvariants have evolved, carrying recent mutations that grant them improved immune evasion abilities. While the BA.1 subvariant caused the biggest variety of infections worldwide between December 2021 and January 2022, each recent subvariant displaced the previous one and exhibited increased neutralization escape.

Studies have found that the variety of cases, the severity of infection, and subsequent hospitalization or mortality varied from one region to a different for every of the subvariants. The geographical variation of the outcomes might be related to the variety of prior infections and vaccination coverage within the country. This study examines the differences in clinical outcomes, viral load, and viral recovery of the varied Omicron subvariants in the US (U.S.).

In regards to the study

The current study used the remnant lateral mid-turbinate nasal or nasopharyngeal swabs from testing symptomatic and asymptomatic patients on the Johns Hopkins Health System (JHHS) between December 2021 and July 2022. The SARS-CoV-2-positive clinical specimens were used for whole genome sequencing.

The clinical and vaccination data of the SARS-CoV-2-positive patients were used to know the clinical outcomes of every subvariant infection corresponding to the vaccination status. The viral loads were calculated based on cycle threshold values (Ct) of the polymerase chain response (PCR) tests.

VeroE6TMPRSS2 (VT) and VeroE6-ACE2-TMPRSS2 (VAT) cell cultures were infected with aliquots of swab specimens to review the recovery of the virus. The cultures were incubated for seven days or until the cytopathic effect (CPE) confirmed infection. The presence of SARS-CoV-2 within the VT and VAT cells was confirmed using reverse transcriptase PCR.

A 50% tissue culture infectious dose (TCID50) assay was used to measure the infectious virus titers in VT and VAT cells. Various statistical analyses similar to Chi-square evaluation, Fisher Exact test, Mann-Whitney U test, and one-way evaluation of variance (ANOVA) were used to look at the correlations between variables.

Results

The outcomes reported that the very best SARS-CoV-2-positivity rates and coronavirus disease 2019 (COVID-19)-related hospitalizations were between December 2021 to January 2022 throughout the dominance of the BA.1 subvariant. The predominance of BA.1.1 and BA.2 between February and April 2022 correlated with decreased cases and hospital admissions.

The emergence of the BA.2.12.1 and BA.5 subvariants resulted in a plateaued increase in cases between May and July 2022. The subvariants that emerged after BA.1 resulted in a slight increase in hospitalizations but reduced mortality.

The authors consider that the variation in hospitalization rates for every subvariant might be attributable to aspects similar to increased home testing with only severe cases searching for hospital admissions, in addition to seasonality with more COVID-19 cases throughout the colder and drier months. The waning of vaccination-induced immunity is also answerable for the rise in hospitalizations for probably the most recent subvariants.

The cell cultures showed reduced recovery of the BA.2 viruses and a corresponding reduction within the variety of cases throughout the predominance of BA.2. This pattern was different from what was observed in other countries similar to China, Japan, and Denmark, indicating the dependence of subvariant emergence, spread, and severity on the immune response aspects inside a community based on prior infections and vaccination coverage.

The study also reported that BA.1 had the very best viral load within the upper respiratory tracts in comparison with all other Omicron subvariants. Moreover, BA.5 exhibited higher transmission and predominance than BA.4 despite having similar spike protein residues and neutralization escape abilities. The 2 subvariants also showed increased re-infection capability in patients with prior BA.1 and BA.1.1 infections. The BA.5 subvariant was also related to higher infectious virus recovery in cell cultures.

Based on the authors, the difference within the recovery of infectious BA.2 and BA.5 subvariant viruses is correlated to the increased immune escape exhibited by BA.5, which contributed to the increased infectivity and rise within the variety of cases during BA.5 dominance.

Conclusions

In summary, the study compared the variety of cases, hospitalization rates, viral load, and viral recovery in cell cultures for the SARS-CoV-2 Omicron subvariants that emerged in November 2021 within the U.S.

The findings indicated that BA.1 was related to the very best variety of infections but had a lower viral load than subsequent Omicron subvariants. Although BA.4 and BA.5 have similar spike protein structures and immune escape abilities, BA.5 exhibited increased transmission and predominance in addition to increased viral recovery from swabs. The study highlights the differential infectability of the Omicron subvariants related to vaccination- and prior infection-induced immunity in various countries.

*Vital notice

medRxiv publishes preliminary scientific reports that usually are not peer-reviewed and, due to this fact, mustn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.