Efficacy of COVID-19 Vaccination on the Symptoms of Patients With Long COVID: A Target Trial Emulation Using Data From the ComPaRe e-Cohort in France

Abstract

Background: Long COVID is a complex multiorgan disorder that can affect patients’ lives severely. Recent reports suggest that symptoms improve after COVID-19 vaccination. Methods: We used data from the ComPaRe long COVID cohort to emulate a target trial evaluating the effect of vaccination among patients with long COVID who still had persistent symptoms at baseline. Vaccinated patients were matched to unvaccinated controls in a 1:1 ratio by their propensity scores. Outcomes, all measured at 120 days after baseline, include disease severity (long COVID ST, range 0-53), rate of complete remission (ie, disappearance of all symptoms), disease impact on patients’ lives (long covid IT, range 0-60), and the proportion of patients reporting an unacceptable symptom state. Vaccinated patients reported all adverse events occurring after vaccination in free text. Findings: In total, 455 patients were allocated to the vaccination group and 455 to the control group; 545 (60·1%) had confirmed infections, and 81 (8·9%) had been hospitalized during their acute COVID-19. By 120 days, vaccination reduced the long COVID symptoms (mean (SD) ST score in the vaccination group 13·0 (9·4) vs. 14·8 (9·8) in the control group; mean difference: -1·8, 95% CI -2·5 to -1·0) and doubled the rate of patients in complete remission (remission rate 16·6% vs 7·5%, HR: 1·97, 95% CI 1·23 to 3·15). Furthermore, vaccination reduced both disease impact on patients’ lives (mean (SD) IT score 24.3 (16·7) vs 27·6 (16·7); mean difference: -3·3, 95% CI -6·2 to -0·5) and the proportion of patients with an unacceptable symptom state (38.9% vs 46.4%, risk difference -7·5%, 95% CI -14·4 to -0·5). In the vaccination group, two (0·4%) patients reported serious adverse events leading to hospitalisation. Interpretation: COVID-19 vaccination lowers the severity and life impact of long COVID at 120 days among patients with persistent symptoms.Funding Information: The authors received no specific funding for this work.Declaration of Interests: The authors declare no competing interests and no financial associations that may be relevant or seen as relevant to the submitted manuscript. The authors have no association with commercial entities that could be viewed as having an interest in the general area of the submitted manuscript.Ethics Approval Statement: All patients provided online consent before participating in the cohort. The Institutional Review Board of Hôtel-Dieu Hospital, Paris, approved the study (IRB: 0008367).