Protection of SARS-CoV-2 natural infection against reinfection with the Omicron BA.4 or BA.5 subvariants

This study estimates the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test-negative, case–control study design. Cases (SARS-CoV-2-positive test results) and controls (SARS-CoV-2-negative test results) were matched according to sex, 10-year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S-gene “target failure” (SGTF) infections between May 7, 2022-July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022-July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a pre-Omicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5’s greater capacity for immune-system evasion than that of BA.1/BA.2. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health, Hamad Medical Corporation, and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with waiver of informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (https://www.moph.gov.qa/english/Pages/default.aspx). Aggregate data are available within the manuscript and its Supplementary information.