Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes

Abstract

Importance: Data about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies.

Objective: To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death.

Design, setting, and participants: Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022.

Exposures: COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.

Main outcomes and measures: Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19-related hospitalization and death.

Results: The median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months.

Conclusions and relevance: Receipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection.

Figure 1.. Effectiveness of Primary Vaccination Series and Prior Infection in Reducing the Risk of SARS-CoV-2 Infection, Hospitalization, or Death

Estimates of effectiveness are shown by solid curves, and 95% CIs are shown by shaded bands. The steep upward trends seen early in panels A-C, but not in panel D, represent the ramp-up period of vaccination. Each curve is truncated at 15 months or when the number at risk hits 15% of the relevant sample. D, Comparison of prior infection with survival to no prior infection among all participants (vaccinated and not), with 98.6% of all participants surviving the prior infection. Home testing for infection is not included. Further detail can be found in eTable 1 in the Supplement.

Figure 2.. Effectiveness of Primary Vaccination Series by Date of First Dose and of Prior Infection by Type of Variant in Reducing the Risk of SARS-CoV-2 Infection, Hospitalization, or Death

A-I, Each batch corresponds to 2 months, but may contain more months to achieve a large number of vaccinated individuals. J-L, Comparison of prior infection with survival to all participants with no prior infection regardless of vaccination status, with 98.6% of all participants surviving the prior infection. Home testing for infection is not included. The color bars indicate predominant variants. Estimates of effectiveness are shown by solid curves, and 95% CIs are shown by shaded bands. Each curve starts at the median date of each batch and is truncated when the number at risk hits 15% of the relevant sample. Further detail, including numbers at risk, can be found in eTable 2 in the Supplement.

Figure 3.. Effectiveness of Booster Vaccination Relative to Primary Series Only by Date of Booster in Reducing the Risk of SARS-CoV-2 Infection, Hospitalization, or Death

The dates of booster were grouped into 2-4 batches, such that each batch contains a large number of booster doses; the US Food and Drug Administration recommended booster doses on September 22, 2021. Home testing for infection is not included. The color bars indicate predominant variants/linages. Estimates of effectiveness are shown by solid curves, and 95% CIs are shown by shaded bands. Each curve starts at the median date of each batch. Further detail, including numbers at risk, can be found in eTable 3 in the Supplement.

Figure 4.. Effectiveness of Booster Vaccination Compared With No Vaccination in Reducing the Risk of SARS-CoV-2 Infection for Receipt of the First Dose in April – May 2021 and Receipt of Booster Dose Between September 22, 2021, and November 30, 2021, by Primary and Booster Combination

Home testing for infection is not included. Estimates of effectiveness are shown by solid curves, and 95% CIs are shown by shaded bands. Further detail can be found in eTable 4 in the Supplement.

Figure 5.. Effectiveness of Booster Vaccination and Prior Infection in Reducing the Risk of SARS-CoV-2 Infection, Hospitalization, or Death Among Participants With Primary Vaccination

C, Comparison of prior infection with survival to no prior infection among all recipients of primary vaccination regardless of boosting status, with 99.2% of primary vaccine recipients surviving the prior infection. Home testing for infection is not included. Estimates of effectiveness are shown by solid curves, and 95% CIs are shown by shaded bands. Results on the outcome of death are not shown in Panels B and C due to a small number of events. The steep upward trends seen early on in panels A and B, but not in panel C, represent the ramp-up period for booster. Each curve is truncated at 15 months or when the number at risk hits 15% of the relevant sample. Further detail can be found in eTable 5 in the Supplement.