The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study

Abstract

Background: Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC.

Methods: RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression.

Findings: Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46-5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183-324) and 181 (147-230) among participants with PASC, and 170 (125-252) and 144 (113-196) among those without PASC, respectively.

Interpretation: Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.

Keywords: COVID-19; Long COVID; Post-acute sequelae; SARS-CoV-2; Therapeutic vaccine; Vaccination.

Fig. 1

Mean number of symptoms during exposure-matched unvaccinated and vaccinated follow-up intervals, among participants with PASC Black vertical bands represent 95% CIs, which were calculated from bootstrapped variance estimates to ensure that variance was independent and identically distributed across participants. Time represents nearest month since first vaccination (for vaccinated participants) or matched time-point (for unvaccinated participants) that symptom survey was completed. P-values were obtained from the Wald χ² test comparing the mean number of symptoms in unvaccinated and vaccinated time-intervals at each month of follow-up, with bootstrapped variance estimates. PASC = Post-acute sequelae of COVID-19.

Fig. 2

IgG binding and spike neutralisation at 30–60 days following illness onset among all participants who did (N = 56) and did not (N = 72) develop PASC, by COVID-19 clinical severity Difference in 30–60 day WT-D614G spike protein neutralising IgG titers and anti-spike and anti-RBD IgG binding titers between those who did and did not develop PASC. The mean effects on neutralising and IgG titers from those who did and did not develop PASC were estimated using a Bayesian multilevel model. Differences in posterior means were mean-centred such that effect sizes shown can be compared on a common scale (top row). Distributions of serum spike protein neutralising IgG titers (bottom left), spike binding (bottom middle) and RBD binding (bottom right) displayed such that each dot represents one participant, coloured according to COVID-19 clinical severity. RBD = Receptor binding domain. PASC = Post-acute sequelae of COVID-19.

Fig. 3

IgG binding and spike neutralisation at 30–60 days following illness onset among participants with mild COVID-19 who did (N = 16) and did not (N = 36) develop PASC Difference in 30–60 day WT-D614G spike protein neutralising IgG titers and anti-spike and anti-RBD IgG binding titers between those who did and did not develop PASC with mild COVID-19. The mean effects on neutralising and IgG titers from those who did and did not develop PASC were estimated using a Bayesian multilevel model. Differences in posterior means were mean-centred such that effect sizes shown can be compared on a common scale (top row). Distributions of serum spike protein neutralising IgG titers (bottom left), spike binding (bottom middle) and RBD binding (bottom right) displayed such that each dot represents one participant. RBD = Receptor binding domain. PASC = Post-acute sequelae of COVID-19.

Fig. 4

Rate of spike- and RBD-binding IgG decay after illness onset, by PASC status at 3 months after illness onset Figures show results of a Bayesian hierarchical linear regression of the log response variable (Y) against time since symptom onset (t), pooling decay rates across participants. Each connected line represents one study participants, coloured by COVID-19 severity. PASC groups were defined as to whether the participant continued to experience one or more symptoms at 3 months after illness onset. Estimated median half-life $\left(t_{1/2}\right)$ and the corresponding 95% credible interval (95CrI) of spike- and RBD-binding IgG levels are computed from the median (black line) and posterior distribution (gray region) of regressed lines. PASC = Post-acute sequelae of COVID-19.