For the publisher:
In early November 2021, the B.1.1.529 (omicron) variant was first identified in South Africa and quickly became the dominant variant in Gauteng province, where a third wave of 2019 coronavirus disease (Covid- 19) caused by virus B. The 1.617.2 (delta) variant was largely reduced. As of November 15, the omicron variant was detected in more than 75% of positive Covid-19 tests that have been sequenced in South Africa1 (Figs. S1 and S2 in the supplementary annex, available with the full text of this letter on NEJM.org). On November 26, the World Health Organization declared omicron a variant of concern. In a study of live virus neutralization tests, omicron was shown to escape antibody neutralization by the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech).2 Thus, data was needed regarding the effectiveness of current vaccines against the omicron variant in preventing hospitalizations for Covid-19.
Using data from Discovery Health, a South African managed care organization, we estimated the vaccine effectiveness of two doses of BNT162b2 vaccine (i.e. one full vaccination) against hospitalization for Covid-19 caused by the omicron variant by analyzing data sets that included the results of polymerase chain reaction (PCR) tests, pre-authorization admission data, a complete history of members’ medical records, records regarding chronic disease and body mass index data to obtain the number of risk factors for Covid-19 per patient, according to guidelines from the Centers for Disease Control and Prevention (CDC).3 Vaccination status was determined from private sector complaint data, and patients who had been vaccinated in the public sector were listed in a vaccine category called âother vaccine typeâ (Table S4). Among fully vaccinated members, we compared the vaccine effectiveness against Covid-19 hospitalization associated with the omicron variant during the period November 15 to December 7 in South Africa, which we have dubbed the dominance proxy. of the omicron variant (omicron proxy period), compared to estimates of vaccine efficacy between September 1 and October 30, when the delta variant was dominant (comparison period).
In our study, we used a negative test design and data exclusion rules to obtain estimates of vaccine efficacy.4 (Table S1), according to the following formula: 1 â odds ratio of Covid-19 hospitalization in the vaccinated population, where the odd ratio was calculated using logistic regression after adjustment for confounding factors age, sex, history Covid-19 infection, week of surveillance, geographic location and number of CDC risk factors. In this analysis, hospitalization related to Covid-19 was a dependent variable and vaccination status was included as an independent variable.
We then performed three sensitivity analyzes on different data subsets during the omicron proxy period. First, we performed PCR tests showing the failure of the S gene target as an indication of omicron infection. Second, we only included PCR results obtained from patients in Gauteng province, given the geographic concentration of the omicron variant during the study period. Third, we limited the results of PCR tests to those obtained from patients who had been hospitalized (eg, respiratory medical admissions), the latter being used as a proxy to identify tests among a symptomatic population (Table S4).
We analyzed 133,437 PCR test results that were obtained during the comparison period, of which 38,155 (28.6%) were obtained at least 14 days after the patient received the second dose of vaccine. For the omicron proxy period, we analyzed 78,173 PCR test results, of which 32,325 (41.4%) were obtained at least 14 days after the second dose (Table 1). The overall positivity of the test was 6.4% during the comparison period and 24.4% during the omicron proxy period, while the Covid-19 admission rate was 10.8% and 2.2%, respectively, as a percentage of the positive results of the PCR test. Patients with positive cases were younger during the omicron proxy period than during the comparison period (Table S3).
During the omicron proxy period, we found a vaccine efficacy of 70% (95% confidence interval [CI], 62 to 76), a conclusion which was confirmed by the results of all sensitivity tests. This measure of vaccine effectiveness was significantly different from that during the comparison period, when the rate was 93% (95% CI, 90 to 94) versus hospitalization for Covid-19 (Table 2).
Thus, during the omicron proxy period, we saw continued efficacy of the BNT162b2 vaccine (albeit at a reduced level) against hospitalization for Covid-19 that was presumed to have been caused by the omicron variant by compared to the rate associated with the delta variant earlier in the year. Adding a booster dose of vaccine may mitigate this reduction in vaccine effectiveness.5
Shirley Collie, B.Sc.
Jared Champion, M.Sc.
Discovery Health, Johannesburg, South Africa
Harry Moultrie, MB, B.Ch.
National Institute of Communicable Diseases, Johannesburg, South Africa
Linda-Gail Bekker, MB, B.Ch., Ph.D.
Desmond Tutu HIV Foundation, Cape Town, South Africa
Glenda Gray, MB, B.Ch.
South African Council for Medical Research, Cape Town, South Africa
Disclosure forms provided by the authors are available with the full text of this letter on NEJM.org.
This letter was posted on December 29, 2021 on NEJM.org.
1. Genomic Surveillance Network in South Africa. SARS-CoV-2 sequencing update. December 3, 2021 (https://www.nicd.ac.za/wp-content/uploads/2021/12/Update-of-SA-sequencing-data-from-GISAID-3-Dec-21-Final.pdf).
2. Pulliam JRC, van Schalkwyk C, Govender N, et al. Increased risk of reinfection with SARS-CoV-2 associated with the emergence of the Omicron variant in South Africa. December 2, 2021 (https://www.medrxiv.org/content/10.1101/2021.11.11.21266068v2). preprint.
3. Centers for Disaster Control and Prevention. Scientific Note: Evidence used to update the list of underlying medical conditions associated with a higher risk of severe COVID-19. October 14, 2021 (https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/underlying-evidence-table.html).
4. Lopez Bernal J, Andrews N, Gower C, et al. Efficacy of Covid-19 vaccines against variant B.1.617.2 (delta). N English J Med 2021; 385:585–594.
5. Barda N, Dagan N, Cohen C, et al. Effectiveness of a third dose of the COVID-19 mRNA vaccine BNT162b2 in preventing serious complications in Israel: an observational study. Lancet 2021; 398:2093–2100.