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[Preprint]. 2022 Oct 7:2022.10.06.22280795.
doi: 10.1101/2022.10.06.22280795.

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program

M Daniel Brannock  1 , Robert F Chew  1 , Alexander J Preiss  1 , Emily C Hadley  1 , Julie A McMurry  2 , Peter J Leese  3 , Andrew T Girvin  4 , Miles Crosskey  5 , Andrea G Zhou  6 , Richard A Moffitt  7 , Michele Jonsson Funk  3 , Emily R Pfaff  3 , Melissa A Haendel  2 , Christopher G Chute  8 ; N3C and RECOVER Consortia
Collaborators, Affiliations

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program

M Daniel Brannock et al. medRxiv. .

Update in

Abstract

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations.

Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design settings and participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C).

Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination.

Main outcomes and measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards.

Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).

Conclusions and relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.

Key points: Question: Does vaccination prior to COVID-19 onset change the risk of long COVID diagnosis?Findings: Four observational analyses of EHRs showed a statistically significant reduction in long COVID risk associated with pre-COVID vaccination (first cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; second cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).Meaning: Vaccination prior to COVID onset has a protective association with long COVID even in the case of breakthrough infections.

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Figures

Figure 1.
Figure 1.
Cohort Definition Flowchart
Figure 2.
Figure 2.. IPTW-Adjusted Kaplan-Meier Curves.
Long COVID events can only be observed in the model-based cohort in 30-day increments, resulting in the observed stair-step structure. A reduced scale is used to highlight the differentiation between the vaccinated and unvaccinated curves.
Figure 3.
Figure 3.. Sensitivity analysis vaccination coefficients for logistic regression (LR) and proportional hazards (PH).
Odds ratios (OR) are shown for LR, hazard ratios (HR) are shown for PH.
See this image and copyright information in PMC

References

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