1. Previous infection, vaccination, and hybrid immunity protected against infection with the omicron variant of coronavirus disease 2019 (COVID-19).

2. Hybrid immunity from previous infection and recent booster vaccination provided the strongest overall protection against the omicron variant.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The omicron variant of SARS-CoV-2 was prevalent from late 2021 into early 2022. It was dominated by the BA.1 subvariant and the BA.2 subvariant. However, the degree of protection against these subvariants provided by previous immunity is uncertain. Furthermore, whether the strongest immunity is induced by previous infection, vaccination, or a hybrid, is also unclear. Therefore, there is a gap in knowledge as to understanding whether protection against omicron infection exists and whether there are differences in immunity conferred via previous infection, vaccination, or a hybrid of both. Overall, this study found that there were no notable differences in effectiveness against omicron of previous infection, vaccination, and hybrid immunity, and all provided strong protection against COVID-19-related hospitalization and death. This study was limited by unexpected biases such as subtle differences or changes in test-seeking behavior, as well as the study population not being generalizable to other countries in which elderly citizens make up a larger proportion of the population. Nevertheless, the study’s findings are significant, as they demonstrate that protection against omicron occurs via previous infection, vaccination, and hybrid immunity, and that hybrid immunity provided the strongest overall protection against infection.

Click to read the study in NEJM

Relevant Reading: Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant

In-Depth [case-control study]: The present study was conducted in Qatar, based on cases of COVID-19 identified from December 2021 through February 2022. Case participants and controls were matched according to sex, 10-year age group, nationality, and week of PCR test. Patients who had COVID-19 tests that occurred within 14 days after the second dose of a COVID-19 vaccination or seven days after the third dose were excluded from the study. The primary outcome was COVID-19 infection based on a positive PCR test. The classification of severe, critical, and fatal COVID-19 cases was based on World Health Organization guidelines. Outcomes in the primary analysis were assessed via frequency distributions and measures of central tendency and compared with the use of standardized mean differences. Based on the primary analysis, the effectiveness of previous infection alone against symptomatic omicron infection was 46.1% (95% Confidence Interval [CI], 39.6 to 51.9). Having received two doses of BNT162b2 vaccination conferred similar effectiveness against symptomatic omicron infection (-1.1%; 95% CI, -7.1 to 4.6). Furthermore, having received three doses of BNT162b2 vaccination had an effectiveness against symptomatic omicron infection of 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection with two doses of BNT162b2 was 55.1% (95% CI, 50.8 to 58.9). Finally,  the effectiveness of previous infection and three doses of BNT162b2 was the highest among all possible immunity groups, with an effectiveness of 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, vaccination alone, and hybrid immunity all conferred strong effectiveness against severe, critical, or fatal COVID-19 due to omicron. Overall, this study showed that there were no significant differences in protection against omicron infection with previous infection, vaccination, or hybrid immunity, though hybrid immunity does offer the strongest protection.

Image: PD

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