Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A Systematic Literature Review
Authors: Rudolph Abby E. , Al Akoury Nadine , Bogdanenko Natalija , Markus Kristen , Whittle Isabelle , Wright Olivia , Haridy Hammam , Spinardi Julia R. , McLaughlin John M. , Kyaw Moe H. 
Published: October 2024

Importance

Existing systematic literature reviews (SLRs) on COVID-19 vaccine effectiveness (VE) against post-COVID-19 conditions (PCC) document high heterogeneity across studies, but have not compared VE across design features known to impact PCC burden or VE against other COVID-19 endpoints.

Objective

This SLR summarizes the evidence across studies among predominately adults that report an adjusted measure of association for the relationship between vaccination and PCC, by timing of vaccination relative to infection or PCC-onset and across different study characteristics.

Evidence review

A comprehensive search strategy was developed within the OVID platform across EMBASE, MEDLINE® and Evidence-Based Medicine reviews, and supplemented with WHO COVID library and Google Scholar® searches, to collate evidence on vaccination and PCC published or posted as pre-prints between January 1st, 2020 and July 18th, 2023. JBI Critical Appraisal Checklists were used to assess each study’s risk of bias.

Findings

This review included 97 studies and synthesized results from 56 studies with low risk of bias that reported adjusted measures for the association between vaccination and PCC. Overall, 77% of pre-infection adjusted VE (aVE) estimates (vs. unvaccinated) were statistically significant (range: 7%–95%), 80% of estimates reflecting a mix of those vaccinated before and after infection were statistically significant (range: 62%–73%), one of five estimates reflecting vaccination after PCC onset was statistically significant (aVE=41%), 43% of post-infection vaccination estimates were statistically significant (two were protective [range: 28%–40%] and one was not [aVE=-47%]), and 46% of estimates not specifying vaccination timing were statistically significant (23 were protective [range: 29%–75%] and one was not [aVE=-132%]). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%–84%) than non-mRNA vaccines (range: 16%–38%) and aVE ranges during (4 studies; range: 10%–70%) and before Omicron predominance (10 studies; range: 7%–50%) overlapped. Pre-infection vaccination was protective regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.

Conclusions and Relevance

Collectively our findings suggest that COVID-19 vaccination received prior to SARS-CoV-2 infection reduces the subsequent risk of developing PCC regardless of the predominant variant circulating.

Key points

Question

Do measures of COVID-19 vaccine effectiveness against post-COVID-19 conditions (PCC) vary by timing of vaccine relative to SARS-CoV-2 infection or PCC onset, vaccine type and number of doses received, PCC definition, predominant SARS-CoV-2 variant, and disease severity?

Findings

COVID-19 vaccination before SARS-CoV-2 infection appeared to reduce the risk of PCC (vs. unvaccinated). Compared with other COVID-19 vaccine types, mRNA vaccines seemed to offer greater protection, and a dose response was observed for mRNA vaccines.

Meaning

Despite heterogeneity across included studies, pre-infection vaccination reduced the risk of ≥1 PCC, regardless of SARS-CoV-2 variant, proportion of sample hospitalized, and PCC definition.