In a recent study posted to the medRxiv* pre-print server, researchers evaluated the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) infections between December 23, 2021, and February 20, 2022, in Qatar to understand how Omicron subvariants, vaccination, and prior infection status impacted these cases.

Study: Effects of BA.1/BA.2 subvariant, vaccination, and prior infection on infectiousness of SARS-CoV-2 Omicron infections. Image Credit: Kuki Ladron de Guevara / Shutterstock

Qatar has an exceptionally young and diverse demographics, where only 9% of its residents are over 50 years of age, and 89% are expatriates from over 150 other countries. Unfortunately, starting December 19, 2021, Qatar experienced a resurgence of coronavirus disease 2019 (COVID-19) cases due to Omicron that peaked by the middle of January 2022. During this time, initially, more cases were reported due to Omicron subvariant BA.1, but within a few days, the other subvariant BA.2 became dominant.

During the Omicron pandemic wave, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) testing, performed at a mass scale in Qatar, helped them diagnose 75% of COVID-19 infections. Every RT-qPCR test recorded the reason for testing, such as contact tracing, random testing campaigns, clinical symptoms, individual requests, routine healthcare testing, pre-travel, at the port of entry, or other. Nearly every resident in Qatar was fully vaccinated against COVID-19 during this time, and the Qatar government had all the COVID-19-related information recorded in their health system. Qatar’s federated SARS-CoV-2 databases even had information on vaccinations performed elsewhere at the port of entry upon arrival to Qatar.

About the study

In the current cross-sectional study, researchers used the real-time RT-qPCR cycle threshold (C_t) value as a proxy for SARS-CoV-2 infectiousness to investigate the effects of Omicron infections in all the residents of Qatar who had an RT-qPCR-confirmed SARS-CoV-2 infection during December 23, 2021, and February 20, 2022.

The researchers sourced all the demographic data from Qatar’s national COVID-19 databases, including reported clinical infections, vaccinations, RT-qPCR tests, and related demographic details since the beginning of the pandemic.

They used the TaqPath COVID-19 combo kit for subvariant status – a SARS-CoV-2 infection with the Omicron BA.1 subvariant was proxied as a spike (S)-gene target failure (SGTF) case, and with the BA.2 subvariant was proxied as a non-SGTF case.

For each study participant, the researchers selected the first positive RT-qPCR-confirmed test. Later, they derived the average C_t value (to be used as the dependent variable) by averaging the C_t values of the nucleocapsid (N), open reading frame 1ab (ORF1ab), and S genes.

Overall, they investigated the extent of COVID-19 spread during the study period based on the information of subvariant causing the infection (BA.1 versus BA.2), vaccination type (BNT162b2 or mRNA-1273), vaccination status (doses, time elapsed since vaccination), prior infection status, RT-qPCR testing reason, study-period week of the test, and demographic factors including sex, age, and nationality.

They used univariable linear regression analyses to evaluate the association of each of these factors with the C_t value. The multivariable linear regression analyses accounting for all covariates estimated associated 95% confidence intervals (CIs) and p-values. The researchers estimated differences between BA.1 and BA.2 infections using standardized mean differences (SMDs).

Study findings

The study analyses covered 156,202 individuals infected with Omicron. Considering C_t values as a measure of SARS-CoV-2 infectiousness, the authors noted that with 3.53 fewer cycles, the BA.2 subvariant appeared substantially more infectious than the BA.1 subvariant.

Proportion of BA.1 (versus BA.2) Omicron infections in the PCR-positive tests assessed using TaqPath COVID-19 Combo Kit during the study period.

C _t values decreased as the time elapsed since vaccination increased, a trend observed for both second and third vaccination doses, reflecting waning vaccine effectiveness over time.

C _t values were 0.86 cycles higher for those receiving booster doses during the months before the RT-qPCR test than for unvaccinated persons. Similarly, the 1.30 cycles higher C _t values among those with a SARS-CoV-2 infection history compared to those with no prior infection signified lower infectiousness of Omicron variant.

Declining C _t values (with age) reflected declining ability to clear SARS-CoV-2 with age. Although there were sex and nationality-based differences in C _t value, these likely reflected test-seeking behaviors of Qatar’s diverse population, having different socio-economic status, and cases with undocumented infections.

The authors observed the lowest C _t values among individuals who seek the RT-PCR test due to COVID-19 symptoms and the highest among those who tested for travel-related purposes. Similarly, they observed lowest C _t values when COVID-19 cases were increasing exponentially during the Omicron wave of December 2021 and were highest after the wave peaked. Later, C _t values declined, as only a small proportion of COVID-19 infections remained recent.

Conclusions

Overall, the study demonstrated that compared to the Omicron BA.1 subvariant, the BA.2 subvariant was more infectious. It rapidly disseminated in Qatar to cause more SARS-CoV-2 infections, as reflected by a higher viral load and longer duration of COVID-19. However, like observed for other SARS-CoV-2 variants, previous infection-induced natural immunity and vaccine-induced immunity resulted in lesser infectious breakthrough infections due to Omicron.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.