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AbstractIntroductionAs of 24 October 2021, 128,868 laboratory-confirmed COVID-19 cases and 3550 deaths were reported from Namibia. The national COVID-19 vaccination campaign that started in March 2021 included health workers (HWs) as a priority group. The vaccines most administered were Sinopharm, AstraZeneca, Pfizer-BioNtech, and Janssen. We aimed to measure the effectiveness of COVID-19 vaccines (VE) amongst HWs against laboratory-confirmed SARS-CoV-2 infection in Namibia. MethodsWe conducted a test negative design (TND) amongst HWs from the two main hospitals treating COVID-19 patients. HWs were defined as all hospital staff over 18 years in direct or indirect contact with patients, eligible for COVID-19 vaccination. We interviewed actively recruited HWs with standardized questionnaires in-person from 25/10/2021 to 25/4/2022. The participants had to state their vaccination status, which was verified through vaccination card, vaccine registry and/or District Health Information System 2. RT-PCR testing of respiratory specimens and serological testing (Wantai and Platelia-ELISA) were conducted. We measured VE by comparing the vaccination status between RT-PCR positive and negative HWs using a multivariable logistic regression model, which was adjusted for confounders. We calculated VE = (1-odds ratio of vaccination)*100 %. ResultsWe included 1201 HWs of which 322 (26.8 %) participants were fully vaccinated with a primary series against COVID-19, 62 (5.2 %) were partially vaccinated and 735 (61.2 %) were not vaccinated. In total, 1119 (93 %) participants had antibodies against SARS-CoV-2 including 637 (90 %) of the unvaccinated participants. Fifty-eight (4.8 %) participants tested RT-PCR positive for SARS-CoV-2. The Omicron variant was detected in all 13 sequenced genomes (11 BA.1.18, 2 BA.1). The estimated overall VE for full vaccination was 61.8 % (95 %-confidence interval, 9.3–83.9 %). ConclusionsThe VE results suggest that COVID-19 vaccines used in Namibia provided good protection from infections with the Omicron variant even if many participants had a SARS-CoV-2 infection before the study. Therefore, COVID-19 vaccines should be administered to risk groups such as HWs independent from previous infections.