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 associate with a relatively high positivity and 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.

Real-life lack of evidence of viable SARS-CoV-2 transmission via inanimate surfaces: The SURFACE study

“…Previous studies found that the recovery of infectious virus from cell culture inversely correlated with the presence of SARS-CoV-2 specific IgG in the respiratory tract, specific for both prior VOCs or monovalent vaccines [19] . Moreover, recovery of infectious virus was more frequent from samples with lower mean Ct values, regardless of the subvariant whereas, when Ct values < 20 were considered, BA.5 showed a statistically higher recovery rate of infectious virus compared with other subvariants [20] . In our study, we did not find viable virus on different surfaces, even if a low Ct was obtained from nasal swabs of the enrolled individuals.…”

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

“…Third, lightly frequency change of T9I (Class II) and P71L (Class III) mutations may affect the virus pathogenicity particularly among milder Omicron sub-variants (Fig.1 e, right). Compared with Omicron BA.1 and BA.2, the clinical symptoms of BA.4 and BA.5 are more severe 9 . Correspondingly, the frequency of T9I dropped 4.30% and 16.65% in the latter two sub-variants, respectively.…”

“…1 e, right). Compared with Omicron BA.1 and BA.2, the clinical symptoms of BA.4 and BA.5 are more severe 9 . Correspondingly, the frequency of T9I dropped 4.30% and 16.65% in the latter two sub-variants, respectively.…”

“…e , The quantification of hospitalization rate and disease severity up to Omicron BA.5 and tabulated the contribution of Class II and III mutations. Pathogenicity of different SARS-CoV-2 variants 9, 12, 13 . f , Heat map of 6 key mutations frequency in Omicron sub-variants.…”

“…In comparison with the original strain and other variants, the pathogenicity of Omicron variants was milder and the rate of hospitalization and mortality were significantly reduced 6 . However, it is worth to note, BA.5 infection has shown increased rate of recovery positive, raised proportion of infections who were "symptomatic" and some patients regained pneumonia symptoms [7][8][9] . These phenomena remind us to be alert to the change in pathogenicity.…”