The effect of SARS-CoV-2 vaccination on post-acute COVID-19 syndrome (PASC): A prospective cohort study 8 241 INTRODUCTION It is now well-recognised that the symptoms of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can persist beyond the acute phase of infection[1, 2]. The World Health Organization (WHO) recently defined this complex syndrome, usually called ‘long COVID’ or ‘postacute COVID-19 syndrome’ (PASC), as the presence of COVID-19 symptoms that occurs within three months after illness onset and persists for at least 2 months[3]. An accurate estimate of the proportion of COVID-19 patients who develop PASC is still lacking, largely due to the substantial heterogeneity in study design and lack of uniform definition [2]. The aetiology of PASC also remains unclear and no treatment options currently exist. As SARS-CoV-2 vaccination programmes are rolled out in many countries, a number of anecdotal reports and case-series from high-income countries have suggested that PASC symptoms can be alleviated after vaccination[4]. An online survey among 900 PASC patients in the United Kingdom found that over half (57.9%) of respondents reported improvement of symptoms following vaccination. Although these findings should be interpreted with caution due to selection bias and lack of a control group, the hypothesis that SARS-CoV-2 could act as a therapeutic vaccine in PASC patients gained traction due to the urgent need for treatment options for PASC. In a recent cohort study of self-referred participants with established PASC, the cumulative rate of complete remission from PASC was higher among vaccinated participants compared to propensity-score matched unvaccinated participants over a 120 day follow-up period[5]. Given that randomised clinical trials in which controls would be prevented from being vaccinated are unethical given the overwhelming benefits of vaccination for both individual and public health, robust clinical data from prospective observational studies are required to confirm or refute these early findings. In addition, complementing clinical data with immunological findings is crucial to examining the possible biological mechanism by which vaccination would contribute to improvement of PASC symptoms. Evaluating antibody kinetics among patients with PASC and those without could help to support any observed beneficial effect of vaccination or lack thereof. For example, a recent prospective cohort study of COVID-19 patients found that IgM and IgG3 levels during primary infection and at 6 months follow-up were lower among patients with PASC compared to those without PASC[6]. Assuming a clinical benefit of vaccination, these findings imply that an effect could be mediated by boosting IgM and IgG3 antibody titers. However, no study to date has explored, within the same
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