COVID-19 severity and vaccine effectiveness in Malawi: A test-negative case-control study.

Background: COVID-19 vaccines were administered globally, and Malawi commenced vaccination on 11 March 2021. Aim: This study assessed the real-world effectiveness of COVID-19 vaccines and factors associated with disease severity and mortality in Malawi. Setting: A facility-based case-control study within the largest referral hospitals. Methods: Cases (COVID-19 positive) were matched 1:1 with controls based on age, sex and testing date. Interviews via phone focused on COVID-19 testing and vaccination, underlying conditions and disease outcomes. Analysed using STATA 17, the exposure of interest was vaccination status. For vaccine effectiveness (VE), conditional logistic regression modelling was used, while disease severity and management were analysed using binary logistic regression. Results: The unvaccinated were at 53.3%, and 35.8% were fully vaccinated and/or received a booster. The VE among the fully and partially vaccinated was 10% (95% CI: -26.2, 35.81) and 31.8% (95% CI: -9.91, 57.72), respectively compared to the unvaccinated. Most of the COVID-19 patients (87.8%) were not hospitalised. Underlying chronic conditions and a previous positive COVID-19 test were associated with severe disease (aOR: 3.54, 95% CI: 1.65, 7.61 and aOR: 2.73, 95% CI: 1.13, 7.61, respectively); however, these odds were not different by vaccination status. Conclusion: The VE was low and severe disease was linked with chronic illnesses and previous positive COVID-19 tests. Efforts to promote vaccination through education and access should be enhanced, particularly for those with underlying chronic conditions. Contribution: The findings can inform strategies on prioritisation for disease vaccination and improving patient outcomes.