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Multicenter Study
. 2022 Feb 16;40(8):1082-1089.
doi: 10.1016/j.vaccine.2022.01.026. Epub 2022 Jan 19.

Impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events following mRNA SARS-CoV-2 vaccination: A nationwide, retrospective cohort study

Lucy L Li  1 , Chunlei Zheng  2 , Jennifer La  3 , Nhan V Do  4 , Paul A Monach  5 , Judith M Strymish  6 , Nathanael R Fillmore  7 , Westyn Branch-Elliman  8
Affiliations
Multicenter Study

Impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events following mRNA SARS-CoV-2 vaccination: A nationwide, retrospective cohort study

Lucy L Li et al. Vaccine. .

Abstract

Background: Previous studies evaluated the SARS-CoV-2 vaccine safety or compared adverse events following vaccination to those from infection. Limited data about the impact of prior infection on post-vaccine adverse events are available. The objective of this study was to evaluate the impact of prior SARS-CoV-2 infection on outcomes shortly after vaccination using a longitudinal design.

Methods: Nationwide, multicenter, retrospective cohort study of hospitalization, death, and pre-specified adverse event rates among Veterans who received mRNA vaccines within the Veterans Health Administration between 12/11/2020 and 8/31/2021. Daily incidence rates were compared before and after vaccine doses, stratified by history of microbiologically-confirmed SARS-CoV-2.

Results: 3,118,802 patients received a first dose and 2,979,326 a second, including 102,829 with a history of SARS-CoV-2 infection. Daily incident hospitalization rates were unchanged before and after the second dose among patients without previous infection (28.8/100,000 post-dose versus 28.6/100,000 pre-dose, p = 0.92). In previously-infected patients, the hospitalization rate increased above baseline one day following vaccination (158.2/100,000 after dose 2 versus 57.3/100,000 pre-dose, p < 0.001), then returned to baseline. Chart review indicated vaccine side effects, such as fever, constitutional symptoms, weakness, or falls, as the definite (39%) or possible (18%) cause of hospitalization. Affected patients had mean age 75, and 90% had at least one serious comorbidity. Hospitalizations were brief (median 2 days), with rapid return to baseline health. Worse baseline health among previously-infected patients prevented conclusions about mortality risk.

Conclusions: Two-dose mRNA vaccine regimens are safe in a population with many comorbidities. Transient increased risks of hospitalization were identified among patients with prior SARS-CoV-2, absolute risk ∼1:1000. Findings support additional study regarding the optimal dosing schedule in this population.

Funding: None.

Keywords: Adverse events; Covid-19; Surveillance; Trigger tools; Vaccination; mRNA vaccine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was unfunded. The VA played no role in the design of the study, data collection, analysis, writing, or submission of the article for publication. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work other than that detailed above, no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig. 1
Fig. 1
Daily incidence of hospitalization per 100,000 Veteran patients during the period from 56 days prior to vaccination and 56 days after vaccination. Panels A and B are for the combined cohort of patients following the first (Panel A) and second (Panel B) doses of vaccine. Panels C and D present the analysis stratified by history of documented SARS-CoV-2 infection within the VA healthcare system following the first (Panel C) and second (Panel D) doses of vaccine. In panels C and D, patients with a history of SARS-CoV-2 infection are represented in blue and patients without a history of SARS-CoV-2 infection are represented in orange. Day 0 is the date of vaccination. Confidence intervals are calculated using a bootstrapping methodology. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
Daily incidence of specific adverse events determined a priori to be of interest, recorded at emergency department visits per 1,000,000 Veteran patients during the period from 56 days prior to vaccination and 56 days after vaccination. Panels A and B are for the combined cohort of patients following the first (Panel A) and second (Panel B) doses of vaccine. Panels C and D present the analysis stratified by history of documented SARS-CoV-2 infection within the VA healthcare system following the first (Panel C) and second (Panel D) doses of vaccine. In panels C and D, patients with a history of SARS-CoV-2 infection are represented in blue and patients without a history of SARS-CoV-2 infection are represented in orange. Day 0 is the date of vaccination. Confidence intervals are calculated using a bootstrapping methodology. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3
Daily incidence of death per 1,000,000 Veteran patients during the period from the date of vaccination until 56 days after vaccination. Panels A and B are for the combined cohort of patients following the first (Panel A) and second (Panel B) doses of vaccine. Panels C and D present the analysis stratified by history of documented SARS-CoV-2 infection within the VA healthcare system following the first (Panel C) and second (Panel D) doses of vaccine. In panels C and D, patients with a history of SARS-CoV-2 infection are represented in blue and patients without a history of SARS-CoV-2 infection are represented in orange. Day 0 is the date of vaccination. Confidence intervals are calculated using a bootstrapping methodology. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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