Effects of BA.1/BA.2 subvariant, vaccination and prior infection on infectiousness of SARS-CoV-2 omicron infections

Compared to BA.1, BA.2 was associated with lower RT-qPCR cycle threshold (Ct) value-3.53 fewer cycles (95% CI: 3.46-3.60), signifying higher infectiousness. This may reflect higher viral load and/or longer duration of infection for BA.2. Natural immunity from previous infection and booster vaccination were associated with less infectious breakthrough infections.

The quantitative reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) value of a SARS-CoV-2 infection represents the inverse of viral load and is correlated with culturable virus; thus, it can be used as a proxy for SARS-CoV-2 infectiousness. 2,3 Accordingly, a low Ct value implies high infectiousness.
Univariable and multivariable regression analyses were conducted to estimate the association between Ct value and each of the Omicron subvariants, mRNA vaccination (factoring dose number and time since vaccination), prior infection, reason for RT-qPCR testing, calendar week of RT-qPCR testing (to account for phases of the rapidly evolving Omicron wave) and demographic factors including sex, age and nationality (Section  Figure S2 shows the process of selecting the study population and Supplementary Table S1 describes the study population characteristics. This was a national study involving 156 202 individuals infected with Omicron who are broadly representative of Qatar's population. To standardize Ct values and ascertain subvariant status, we analysed only RT-qPCR-confirmed infections diagnosed with TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, USA), used to process most RT-qPCR tests in Qatar. 3 Compared with BA.1, BA.2 was associated with 3.53 fewer cycles (95% confidence interval [CI]: 3.46-3.60), signifying higher infectiousness (Table 1). Ct value decreased with time The two-tailed F-test of the univariable analysis. b RT-qPCR Ct value was adjusted for age-group, sex, nationality, Omicron subvariant, reason for RT-qPCR test, RT-qPCR test studyperiod week, vaccination status and prior SARS-CoV-2 infection. c The 10-19 age group was chosen as a reference, and not the < 10-age group, because of the different manifestations of this infection in small children. d Nationalities were chosen to represent the most populous groups on Qatar. e These comprise 44 other nationalities in Qatar. f An RT-qPCR-positive test that occurred < 90 days before the study RT-qPCR-positive test was included separately in the analysis, but was not considered a prior infection. This RT-qPCR-positive test and the study RT-qPCR-positive test may both reflect the same prolonged infection. g Prior infection was defined as an RT-qPCR-positive test that occurred ≥90 days before the RT-qPCR-positive test that is included in the study.
since second and third vaccinations, mirroring the established pattern of waning vaccine effectiveness. 4 Ct values were highest for those who received their boosters in the month preceding the RT-qPCR test-0.86 cycles (95% CI: 0.72-1.00) higher than for unvaccinated persons. Ct value was 1.30 (95% CI: 1.20-1.39) cycles higher for those with a prior infection compared with those without prior infection, signifying lower infectiousness. Ct value declined gradually with age (Table 1), perhaps reflecting slower virus clearance with aging. There were differences in Ct value by sex and nationality, but these may reflect different test-seeking behaviours for different socioeconomic groups in Qatar's diverse population. Ct value was lowest for those who were tested because of symptoms and was highest for those who were tested for travel-related purposes. Ct value was lowest during the exponential-growth phase of the Omicron wave, as a large proportion of infections were recent, and was highest after the wave peaked and was declining, as a small proportion of infections were recent. Stratified analyses for BA.1 and BA.2 showed similar findings (Supplementary Tables S2 and S3). Limitations are discussed in Section S2.
The BA.2 subvariant appears substantially more infectious than the BA.1 subvariant, consistent with findings of a household study from Denmark. 5 This may reflect higher viral load and/or longer duration of infection, thereby explaining the rapid expansion of this subvariant in Qatar (Supplementary Figure S1). Natural immunity from previous infection and strength of vaccine immunity correlates with less infectious breakthrough infections, as observed for earlier SARS-CoV-2 variants. 3 Symptomatic infection and older age are associated with higher infectiousness.

Supplementary data
Supplementary data are available at JTM online.

Author contributions
S.H.Q. co-designed the study, performed the statistical analyses and co-wrote the first draft of the article. H.C. co-designed the study, supported the statistical analyses and co-wrote the first draft of the article. L.J.A. conceived and co-designed the study, led the statistical analyses and co-wrote the first draft of the article. P.T. and M.R.H. conducted the multiplex, RT-qPCR variant screening and viral genome sequencing. H.Y., H.A.K. and M.S. conducted viral genome sequencing. All authors contributed to data collection and acquisition, database development, discussion and interpretation of the results, and to the writing of the manuscript. All authors have read and approved the final manuscript.