Assessing COVID-19 vaccine effectiveness against long COVID

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Oct 19 2023

In a recent study published in Antimicrobial Stewardship & Healthcare Epidemiology, researchers discuss severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness (VE) in preventing post-coronavirus disease 2019 (COVID-19) conditions such as long COVID in fully vaccinated individuals.

Study: The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: A systematic literature review and meta-analysis of the latest research. Image Credit: Treecha / Shutterstock.com

Background

Extensive scientific research has confirmed the efficacy and safety of SARS-CoV-2 vaccines in reducing hospitalization and mortality rates. In addition, several studies have highlighted the benefits of additional SARS-CoV-2 vaccinations in sustaining vaccine-conferred immunity against emerging SARS-CoV-2 variants of concern (VOCs).

Long COVID can present with persistent neuropsychiatric, respiratory, and cardiovascular symptoms four or more weeks an acute SARS-CoV-2 infection. Long COVID has raised significant public health concerns, as a sizeable proportion of individuals develop long COVID symptoms and associated complications that significantly impact the quality of life and pose a considerable healthcare burden.

With progress in vaccination campaigns, most individuals have received at least one COVID-19 vaccine dose. However, COVID-19 VE against long COVID in fully vaccinated people remains uncertain and may vary by the number of vaccine doses received by individuals.

About the study

In the present meta-analysis, researchers investigate COVID-19 VE against long COVID.

Databases such as the Cumulative Index to Nursing and Allied Health, PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Scopus were searched between December 1, 2019, and June 2, 2023, for records evaluating VE against long COVID among individuals who had received two COVID-19 vaccinations. Only original research articles and observational studies published in scientific, peer-reviewed journals, including unvaccinated and completely vaccinated individuals, evaluating long-term COVID-19 VE were included.

Individuals were vaccinated with two doses of vector-based, inactivated viral, or messenger ribonucleic acid (mRNA) vaccines or a single dose of the Ad26.COV2.S (Janssen) vaccine. Commentaries, editorials, study protocols, reviews, and studies analyzing the effectiveness of only one dose of SARS-CoV-2 vaccines, including children, were excluded from the analysis.

Long COVID was described as the presence of symptoms for at least four weeks following acute SARS-CoV-2 infection. Bias risks were evaluated using the Downs and Black scale. 

Two researchers independently performed component quality assessments and resolved disagreements by consensus. The diagnostic odds ratio (DOR) was calculated for long COVID between double-dose COVID-19 vaccinees and their unvaccinated counterparts after pooling values from all included studies. The team estimated VE as 100% multiplied by the (1-DOR) value.

Study findings

After excluding 107 records that did not meet the eligibility criteria, 32 studies that consisted of 775,931 people, were selected for the systematic review, of which 24 (620,221 individuals) were considered for meta-analysis. Of the 32 studies, 22, 16, 12, 10, two, one, one, and one analyzed the effectiveness of the Pfizer/BioNTech, Moderna, Janssen, AstraZeneca, CoronaVac, Covaxin, Sinopharm, and Gamaleya COVID-19 vaccines, respectively.

The pooled long COVID prevalence rates were 12% and 5.3% among unvaccinated and fully vaccinated individuals, respectively. The pooled DOR for long COVID in fully vaccinated individuals was 0.7, with a VE estimate of 32%. VE values were 37% and 69% among individuals who received double and triple COVID-19 vaccinations before the SARS-CoV-2 infection, respectively.

COVID-19 vaccines did not protect individuals against long COVID who were vaccinated after the SARS-CoV-2 infection. Complete vaccination before contracting SARS-CoV-2 significantly reduced long COVID incidence across different COVID-19 waves, including the SARS-CoV-2 Omicron VOC wave.

Increased VE was observed among individuals who received supplementary doses. In particular, three studies evaluated long COVID risk among individuals who received booster doses before SARS-CoV-2 infection, with a DOR of 0.3 and a VE estimate of 69%.

Among seven studies evaluating long COVID risk among individuals who received SARS-CoV-2 vaccines before COVID-19 during Omicron predominance, the DOR was 0.7 with a VE estimate of 32%.

These findings were homogeneous among the included studies and there was no publication bias among the studies included in the meta-analysis. Concerning evidence quality among 32 studies, 28, three, and one were of good, fair, and poor quality, respectively.

Conclusions

The study findings indicate a significantly lower long COVID risk among fully vaccinated individuals as compared to unvaccinated individuals. Additional COVID-19 vaccinations before an individual contracted SARS-CoV-2 increased VE.

The pooled long COVID prevalence was 12% among unvaccinated individuals and 5.3% among fully vaccinated individuals. The low prevalence rates could be because most of the included individuals were non-hospitalized and developed Omicron infections.

A more standardized long COVID definition is required for researchers to evaluate the true prevalence among unvaccinated and vaccinated individuals and assess VE against long COVID.

Future studies, including more uniform study designs and controlling for potential confounding factors such as age, medical history, immunosuppression status, prior COVID-19 history, and diverse populations from various geographic regions, must be conducted to improve the generalizability of the findings. Additional studies must also evaluate the impact of time-dependent effects such as SARS-CoV-2 VOC emergence, waning immunity, vaccine boosters, and bivalent VE against long COVID.