Protection from previous natural infection compared with mRNA vaccination against SARS-CoV-2 infection and severe COVID-19 in Qatar: a retrospective cohort study

Background Understanding protection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination is important for informing vaccine mandate decisions. We compared protection conferred by natural infection versus that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar. Methods We conducted two matched retrospective cohort studies that emulated target trials. Data were obtained from the national federated databases for COVID-19 vaccination, SARS-CoV-2 testing, and COVID-19-related hospitalisation and death between Feb 28, 2020 (pandemic onset in Qatar) and May 12, 2022. We matched individuals with a documented primary infection and no vaccination record (natural infection cohort) with individuals who had received two doses (primary series) of the same vaccine (BNT162b2-vaccinated or mRNA-1273-vaccinated cohorts) at the start of follow-up (90 days after the primary infection). Individuals were exact matched (1:1) by sex, 10-year age group, nationality, comorbidity count, and timing of primary infection or first-dose vaccination. Incidence of SARS-CoV-2 infection and COVID-19-related hospitalisation and death in the natural infection cohorts was compared with incidence in the vaccinated cohorts, using Cox proportional hazards regression models with adjustment for matching factors. Findings Between Jan 5, 2021 (date of second-dose vaccine roll-out) and May 12, 2022, 104500 individuals vaccinated with BNT162b2 and 61 955 individuals vaccinated with mRNA-1273 were matched to unvaccinated individuals with a documented primary infection. During follow-up, 7123 SARS-CoV-2 infections were recorded in the BNT162b2-vaccinated cohort and 3583 reinfections were recorded in the matched natural infection cohort. 4282 SARS-CoV-2 infections were recorded in the mRNA-1273-vaccinated cohort and 2301 reinfections were recorded in the matched natural infection cohort. The overall adjusted hazard ratio (HR) for SARS-CoV-2 infection was 0 center dot 47 (95% CI 0 center dot 45-0 center dot 48) after previous natural infection versus BNT162b2 vaccination, and 0 center dot 51 (0 center dot 49-0 center dot 54) after previous natural infection versus mRNA-1273 vaccination. The overall adjusted HR for severe (acute care hospitalisations), critical (intensive care unit hospitalisations), or fatal COVID-19 cases was 0 center dot 24 (0 center dot 08-0 center dot 72) after previous natural infection versus BNT162b2 vaccination, and 0 center dot 24 (0 center dot 05-1 center dot 19) after previous natural infection versus mRNA-1273 vaccination. Severe, critical, or fatal COVID-19 was rare in both the natural infection and vaccinated cohorts. Interpretation Previous natural infection was associated with lower incidence of SARS-CoV-2 infection, regardless of the variant, than mRNA primary-series vaccination. Vaccination remains the safest and most optimal tool for protecting against infection and COVID-19-related hospitalisation and death, irrespective of previous infection status. Funding The Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, Weill Cornell Medicine-Qatar; Qatar Ministry of Public Health; Hamad Medical Corporation; Sidra Medicine; Qatar Genome Programme; and Qatar University Biomedical Research Center. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Automated summary

This study compared the protection against SARS-CoV-2 infection provided by natural infection and COVID-19 vaccination. The results showed that natural infection was associated with a lower risk of SARS-CoV-2 infection, but vaccination remained the safest and most optimal tool for protection.