In those with post-acute sequelae of COVID-19 (PASC), COVID-19 vaccination did not show a strong therapeutic effect with respect to the patient’s number of symptoms or likelihood of full recovery. These were among findings of a cohort study published in the journal Vaccine.

Although symptoms of PASC may improve following SARS-CoV-2 vaccination, few prospective data are available to explore the underlying mechanisms, noted researchers for the current study. They therefore sought to evaluate the effect of vaccination on symptomatology among individuals with PASC. The study also compared antibody dynamics in those with PASC vs those without PASC.

Researchers in The Netherlands identified adults with PASC from the RECoVERED cohort study of individuals in Amersterdam who had been infected with mild to critical COVID-19 between May 2020 and June 2021. All cohort participants were enrolled from the onset of their illness. Among participants with PASC, vaccinated individuals were exact-matched in a 1:1 ratio with unvaccinated participants with respect to age, sex, obesity status, and time since the onset of illness.

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Investigators compared the monthly mean number of symptoms over a 3-month follow-up period between the matched pairs. Exact logistic regression was used to compare the percentage of participants in each group — that is, those vaccinated vs unvaccinated — who recovered fully from PASC. Bayesian hierarchical linear regression was used to evaluate the association between PASC status and rate of decay of spike-binding and receptor-binding domain (RBD) immunoglobulin G (IgG) titers up to 9 months following disease onset.

At least 3 months of follow-up data was available for 316 of the 349 participants. Of those 316 participants, 58.9% (186) developed PASC. Those who developed PASC were older (P <.001), and more often had moderate or severe/critical COVID-19 (P <.001), a higher BMI (P =.002), and a greater likelihood to report a lower level of education (P <.001), compared with those who fully recovered from their symptoms within 3 months of onset of illness. Although all of the participants were unvaccinated for COVID-19 prior to enrollment, the majority of them had been vaccinated against SARS-CoV-2 by November 1, 2021.

Among the 36 matched pairs with PASC, the mean number of symptoms reported each month during the 3-month follow-up period was comparable in the vaccinated and the unvaccinated groups. The likelihood of full recovery from PASC did not differ between the matched pairs (odds ratio, 1.57; 95% CI, 0.46-5.84) within 3 months following the matched time point.

The median half-lives of spike-binding and RBD-binding IgG levels were 233 days (95% CI, 183-324 days) and 181 days (95% CI, 147-230 days), respectively, among participants with PASC. The corresponding values were 170 days (95% CI, 125 -252 days) and 144 days (95% CI, 113-196 days), respectively, among participants without PASC.

Several limitations of the current study should be noted. Although the researchers utilized a robust statistical method to match cases and controls, because vaccination was not randomly assigned, residual confounding might still exist. Another limitation — which is faced by all PASC studies without SARS-CoV-2 negative controls — is the fact that uncertainty remains as to what extent the symptoms recorded were causally related to SARS-CoV-2 infection, as opposed to being associated with either an individual’s underlying comorbidities or with the psychological and physical impact of the pandemic.

The researchers concluded that the current study results indicate that vaccination does not improve symptoms of PASC. This finding was further supported by the finding of comparable spike-binding and RBD-binding IgG waning trajectories between those with and without PASC, thus refuting any immunologic basis for a therapeutic effect of vaccination on PASC. An understanding of the biologic mechanism underlying PASC is needed to inform effective preventive measures and therapeutic options, the study authors noted.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Wynberg E, Han AX, Boyd A, et al; RECoVERED Study Group. The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): a prospective cohort study. Vaccine. Published online June 7, 2022. doi:10.1016/j.vaccine.2022.05.090