Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland

Fasih Haider; Thiago Cerqueira-Silva; Kirsten J. Hainey; Tristan Millington; Syed Ahmar Shah; Vincius de Araujo Oliveira; Neil Pearce; Mauricio L. Barreto; Viviane Sampaio Boaventura; Srinivasa Vittal Katikireddi; Chris Robertson; Manoel Barral-Netto; Aziz Sheikh

doi:10.1136/bmjopen-2025-104057

Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland

Fasih Haider, Thiago Cerqueira-Silva, Kirsten J. Hainey, Tristan Millington, Syed Ahmar Shah, Vincius de Araujo Oliveira, Neil Pearce, Mauricio L. Barreto, Viviane Sampaio Boaventura, Srinivasa Vittal Katikireddi, Chris Robertson, Manoel Barral-Netto, Aziz Sheikh

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Abstract

Objectives: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland.

Design: We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil.

Setting and participants: We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022.

Outcome measures: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection.

Results: From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: <6 months postprimary infection: Brazil OR 0.10 (95% CI 0.09 to 0.11), Scotland OR 0.01 (95% CI 0.00 to 0.05); >12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: <6 months postprimary infection: OR 0.19 (95% CI 0.19 to 0.20); >12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)).

Conclusion: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.

Original language	English
Article number	e104057
Number of pages	10
Journal	BMJ Open
Volume	15
Issue number	7
DOIs	https://doi.org/10.1136/bmjopen-2025-104057
Publication status	Published - 16 Jul 2025

Funding

his study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through the Health Data Research UK. This research is part of the Data and Connectivity National Core Studies, led by Health Data Research UK, in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant reference: MC_PC_20058). Additional support has been provided through Public Health Scotland, the Scottish Government Director-General Health and Social Care and The University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). SVK acknowledges funding from an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the MRC (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). KJH acknowledges funding from MRC (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (CAF/22/16 and SPHSU17). TC-S acknowledges funding from the Royal Society (NIF\R1\231435). VSB, MLB and MB-N are Brazilian National Research Council research fellows. This partnership between Brazil and Scotland was established through funding from the NIHR (GHRG/16/137/99) using UK aid from the UK government to support global health research.

Keywords

SARS-CoV-2
natural immunity
reinfection
COVID-19
Omicron

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Haider, F., Cerqueira-Silva, T., Hainey, K. J., Millington, T., Shah, S. A., de Araujo Oliveira, V., Pearce, N., Barreto, M. L., Sampaio Boaventura, V., Katikireddi, S. V., Robertson, C., Barral-Netto, M., & Sheikh, A. (2025). Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland. BMJ Open, 15(7), Article e104057. https://doi.org/10.1136/bmjopen-2025-104057

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title = "Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland",

abstract = "Objectives: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland. Design: We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95\% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil. Setting and participants: We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022. Outcome measures: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection. Results: From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: <6 months postprimary infection: Brazil OR 0.10 (95\% CI 0.09 to 0.11), Scotland OR 0.01 (95\% CI 0.00 to 0.05); >12 months postprimary infection: Brazil OR 0.12 (95\% CI 0.10 to 0.14), Scotland OR 0.03 (95\% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: <6 months postprimary infection: OR 0.19 (95\% CI 0.19 to 0.20); >12 months postprimary infection: OR 0.42 (95\% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95\% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95\% CI 0.12 to 0.19)). Conclusion: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.",

keywords = "SARS-CoV-2, natural immunity, reinfection, COVID-19, Omicron",

author = "Fasih Haider and Thiago Cerqueira-Silva and Hainey, \{Kirsten J.\} and Tristan Millington and Shah, \{Syed Ahmar\} and \{de Araujo Oliveira\}, Vincius and Neil Pearce and Barreto, \{Mauricio L.\} and \{Sampaio Boaventura\}, Viviane and Katikireddi, \{Srinivasa Vittal\} and Chris Robertson and Manoel Barral-Netto and Aziz Sheikh",

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day = "16",

doi = "10.1136/bmjopen-2025-104057",

language = "English",

volume = "15",

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Haider, F, Cerqueira-Silva, T, Hainey, KJ, Millington, T, Shah, SA, de Araujo Oliveira, V, Pearce, N, Barreto, ML, Sampaio Boaventura, V, Katikireddi, SV, Robertson, C, Barral-Netto, M & Sheikh, A 2025, 'Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland', BMJ Open, vol. 15, no. 7, e104057. https://doi.org/10.1136/bmjopen-2025-104057

TY - JOUR

T1 - Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection

T2 - analyses of national data for Brazil and Scotland

AU - Haider, Fasih

AU - Cerqueira-Silva, Thiago

AU - Hainey, Kirsten J.

AU - Millington, Tristan

AU - Shah, Syed Ahmar

AU - de Araujo Oliveira, Vincius

AU - Pearce, Neil

AU - Barreto, Mauricio L.

AU - Sampaio Boaventura, Viviane

AU - Katikireddi, Srinivasa Vittal

AU - Robertson, Chris

AU - Barral-Netto, Manoel

AU - Sheikh, Aziz

PY - 2025/7/16

Y1 - 2025/7/16

N2 - Objectives: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland. Design: We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil. Setting and participants: We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022. Outcome measures: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection. Results: From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: <6 months postprimary infection: Brazil OR 0.10 (95% CI 0.09 to 0.11), Scotland OR 0.01 (95% CI 0.00 to 0.05); >12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: <6 months postprimary infection: OR 0.19 (95% CI 0.19 to 0.20); >12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)). Conclusion: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.

AB - Objectives: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland. Design: We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil. Setting and participants: We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022. Outcome measures: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection. Results: From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: <6 months postprimary infection: Brazil OR 0.10 (95% CI 0.09 to 0.11), Scotland OR 0.01 (95% CI 0.00 to 0.05); >12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: <6 months postprimary infection: OR 0.19 (95% CI 0.19 to 0.20); >12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)). Conclusion: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.

KW - SARS-CoV-2

KW - natural immunity

KW - reinfection

KW - COVID-19

KW - Omicron

U2 - 10.1136/bmjopen-2025-104057

DO - 10.1136/bmjopen-2025-104057

M3 - Article

SN - 2044-6055

VL - 15

JO - BMJ Open

JF - BMJ Open

IS - 7

M1 - e104057

ER -

Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland

Abstract

Funding

Keywords

UN SDGs

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