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Risk of SARS-CoV-2 Reinfection and COVID-19 Hospitalisation in Individuals With Natural- and Hybrid Immunity: A Retrospective, Total Population Cohort Study in Sweden
30 Pages Posted: 4 Jan 2022More...
Background: Real-world evidence supporting Coronavirus disease 2019 (Covid-19) vaccination in individuals who have recovered from a previous infection is lacking.
Methods: Three cohorts were formed using Swedish nationwide registries. The first (N=2,039,106) included unvaccinated individuals with a documented previous SARS-CoV-2 infection (natural immunity), matched pairwise to unvaccinated individuals without natural immunity at baseline. The second (N=962,318) and third cohort (N=567,810) included individuals vaccinated with one (one-dose hybrid immunity) or two doses (two-dose hybrid immunity), respectively, after a previous infection, matched pairwise to individuals with natural immunity at baseline.
Findings: After the first three months, natural immunity was associated with 95% (adjusted hazard ratio [aHR], 0·05, 95% CI, 0·05-0·05, P<0·001) lower risk of SARS-CoV-2 reinfection and 87% (aHR, 0·13, 95% CI, 0·11-0·16, P<0·001) lower risk of Covid-19 hospitalisation for up to 20 months of follow-up. Compared to natural immunity, one-dose hybrid immunity was associated with 58% lower risk of SARS-CoV-2 reinfection (aHR, 0·42, 95% CI, 0·38-0·47, P<0·001) the first two months, with evidence of attenuation during up to 9 months (P<0·001) of follow up. Two-dose hybrid immunity was associated with 66% lower risk of SARS-CoV-2 reinfection (aHR, 0·34, 95% CI, 0·31-0·39, P<0·001), with no evidence of attenuation (P=0·07). The reduced risk of SARS-CoV-2 reinfection associated with two-dose hybrid immunity was observed only for mRNA-based vaccines (aHR, 0·32, 95% CI, 0·28-0·37, P<0·001), but not ChAdOx1 nCoV-19 (aHR, 0·75, 95% CI, 0·41-1·37, P=0·35). Both one-dose (aHR, 0·06, 95% CI, 0·03-0·12, P<0·001) and two-dose (aHR, 0·10, 95% CI, 0·04-0·22, P<0·001) hybrid immunity was associated with lower risk of Covid-19 hospitalisation compared to natural immunity.
Interpretation: The risk of SARS-CoV-2 reinfection and Covid-19 hospitalisation in individuals who have recovered from a previous infection remained low for up to 20 months. Vaccination with an mRNA vaccine seemed to further decrease the risk, although the differences in absolute measures were small. In countries with limited vaccine supply, high-risk individuals without any immunity should be prioritized for vaccination.
Funding Information: The present study was not funded.
Declaration of Interests: None.
Ethics Approval Statement: The present study was approved by the Swedish Ethical Review Authority (number 495/2021), who waived the requirement of obtaining informed consent given the retrospective study design.
Note: This paper has been published in THE LANCET Infectious Diseases, Published:March 31, 2022, DOI: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00143-8/fulltext
Keywords: Covid-19 infection, vaccination, Natural immunity
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