Protective Effectiveness of Natural SARS-CoV-2 Infection and Vaccines against Omicron BA.4/BA.5 and XBB Reinfection in Singapore: A National Cohort Study

30 Pages Posted: 3 Jan 2023

See all articles by Celine Y. Tan

Celine Y. Tan

Ministry of Health, Singapore

Calvin J. Chiew

National Centre for Infectious Diseases, Singapore; Ministry of Health, Singapore

Deanette Pang

Ministry of Health, Singapore

Vernon J. Lee

Ministry of Health, Singapore

Benjamin Ong

Ministry of Health, Singapore

David Chien Lye

National Centre for Infectious Diseases; Tan Tock Seng Hospital; Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine; National University of Singapore (NUS) - Yong Loo Lin School of Medicine

Kelvin Bryan Tan

Ministry of Health, Singapore

Date Written: December 21, 2022

Abstract

Background: Despite a large proportion of the population vaccinated and naturally infected, Singapore experienced SARS-CoV-2 waves driven by Omicron BA.5 and XBB sublineages. Data on the protective effectiveness of previous SARS-CoV-2 infections and vaccinations against Omicron BA.4/BA.5 and XBB reinfections remain scarce, and can be derived from Singapore’s experience as one of the first countries with an XBB-driven wave.

Methods: Using official databases from the Singapore Ministry of Health, we conducted a retrospective cohort study among Singapore residents aged ≥18 years to assess hybrid immunity against BA.4/BA.5 reinfections from 1 October 2022 to 1 November 2022 and XBB reinfections from 18 October 2022 to 1 November 2022. Analysis stratified by time from first infection was also conducted to analyse waning immunity. Incidence rate ratios (IRR) were measured by Poisson regressions, with SARS-CoV-2-naive individuals as the reference group. Protective effectiveness (PE) was calculated by taking one minus the risk ratio.

Findings: 2,456,791 individuals were included, contributing 53.1 million person-days of observation for the SARS-CoV-2-naive group, and 3.4, 6.6 and 13.7 million person-days to the groups with previous pre-Omicron, BA.1 and BA.2 infections respectively between 1 October 2022 and 1 November 2022. Compared with naïve individuals, first infections with pre-Omicron variants did not confer protection against BA.4/BA.5 (IRR 0.87 [95% CI 0.73–1.05] for pre-Omicron infection with booster) or XBB reinfection (IRR 1.29 [95% CI 1.23–1.35] for pre-Omicron infection with booster). Prior BA.2 infection with boosters provided the greatest protection, but this was lower against reinfection with XBB (PE 51%; 95% CI 49–53%) than BA.4/BA.5 (78%; 95% CI 74–82%). Protection by BA.2 against XBB reinfection also waned faster (74% [95% CI 72–75%) at 3–6 months to 49% [95% CI 47–52%] at 7–8 months) compared with BA.4/BA.5 reinfection (87% [95% CI 82–90%] at 3–6 months to 74% [95% CI 66–80%] at 7–8 months) over time from first infection.

Interpretation: Protection from an earlier Omicron infection with vaccination against XBB reinfection was lower and waned faster than that for BA.4/BA.5 reinfection, indicative of XBB’s greater immune evasiveness. Populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and natural infection, reflected by high reinfection rates during Singapore’s XBB wave.

Note:
Funding declaration: This study was not funded.

Conflict of Interests: The authors declare that they have no conflict of interest.

Keywords: COVID-19, SARS-CoV-2, vaccines, SARS-CoV-2 variants, hybrid immunity

Suggested Citation

Tan, Celine Y. and Chiew, Calvin J. and Pang, Deanette and Lee, Vernon J. and Ong, Benjamin and Lye, David Chien and Tan, Kelvin Bryan, Protective Effectiveness of Natural SARS-CoV-2 Infection and Vaccines against Omicron BA.4/BA.5 and XBB Reinfection in Singapore: A National Cohort Study (December 21, 2022). Available at SSRN: https://ssrn.com/abstract=4308740 or http://dx.doi.org/10.2139/ssrn.4308740

Celine Y. Tan (Contact Author)

Ministry of Health, Singapore ( email )

College of Medicine
16 College Road
Singapore, 169854
Singapore

Calvin J. Chiew

National Centre for Infectious Diseases, Singapore

Singapore

Ministry of Health, Singapore ( email )

College of Medicine
16 College Road
Singapore, 169854
Singapore

Deanette Pang

Ministry of Health, Singapore ( email )

Vernon J. Lee

Ministry of Health, Singapore ( email )

College of Medicine
16 College Road
Singapore, 169854
Singapore

Benjamin Ong

Ministry of Health, Singapore ( email )

College of Medicine
16 College Road
Singapore, 169854
Singapore

David Chien Lye

National Centre for Infectious Diseases

Singapore

Tan Tock Seng Hospital

11 Jalan Tan Tock Seng
308433
Singapore

Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine

Singapore

National University of Singapore (NUS) - Yong Loo Lin School of Medicine

Singapore

Kelvin Bryan Tan

Ministry of Health, Singapore ( email )

College of Medicine
16 College Road
Singapore, 169854
Singapore

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