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Background — The objective of this study was to investigate how protection against COVID-19 conferred by previous infection is modified by vaccination. Methods — In a cohort of all 152655 individuals in Scotland alive at 90 days after a positive test for SARS-CoV-2 (confirmed by cycle threshold < 30, or two tests) followed till 22 September 2021, rate ratios for reinfection were estimated with calendar time or tests as timescale. Findings — Rates of detected and hospitalised reinfection with COVID-19 while unvaccinated were respectively 6.8 (95% CI 6.4 to 7.2) and 0.18 (95% CI 0.12 to 0.25) per 1000 person-months. These rates were respectively 68% and 74% lower than in a matched cohort of individuals who had not previously tested positive. Efficacy of two doses of vaccine in those with previous infection was estimated as as 84% (95 percent CI 81% to 86%) against detected reinfection and 71% (95 percent CI 29% to 88%) against hospitalised or fatal reinfection. The rate of detected reinfection after two doses of vaccine was 1.35 (95% CI 1.02 to 1.78) times higher in those vaccinated before first infection than in those unvaccinated at first infection. Interpretation — The combination of natural infection and vaccination provides maximal protection against new infection with SARS-CoV-2: prior vaccination does not impair this protection.

Competing Interest Statement

HC receives research support and honoraria and is a member of advisory panels or speaker bureaus for Sanofi Aventis, Regeneron, Novartis, Novo-Nordisk and Eli Lilly. HC receives or has recently received non-binding research support from AstraZeneca and Novo-Nordisk

Funding Statement

No specific funding was received for this study. HC is supported by an endowed chair from the AXA foundation

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was performed within Public Health Scotland as part of its statutory duty to monitor and investigate public health problems. Under the [UK Policy Framework for Health and Social Care Research]( set out by the NHS Health Research Authority, this does not fall within the definition of research and ethical review was therefore not required. This has been confirmed in writing by the NHS West of Scotland Research Ethics Service.

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.


I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as 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).


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.


Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

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