The effect of COVID-19 vaccination on long COVID symptoms

In a recent study posted to the Research Square* preprint server and under consideration at a Nature Portfolio Journal, researchers assessed the effectiveness of coronavirus disease 2019 (COVID-19) vaccines in patients experiencing long COVID.

Study: 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. Image Credit: Starocean/ShutterstockStudy: 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. Image Credit: Starocean/Shutterstock

COVID-19 cases, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have surpassed 420 million cases globally. Although the disease subsides within 14 days, some infected individuals experience a long-form of COVID-19 (long COVID) wherein the symptoms linger for a prolonged period, i.e., several months after initial infection.

Long COVID can cause multiorgan dysfunction and adversely impact the lives of patients. According to one study, over 85% of the long COVID patients complain of lingering symptoms even after a year post-onset. There is no treatment for long COVID other than general advice, multidisciplinary rehabilitation, and self-management. However, it has been speculated that vaccination against SARS-CoV-2 can help ameliorate long COVID, but there is little evidence to support this notion.

The study

In the current study, researchers carried out a target trial emulation to evaluate the effects of vaccination on the symptoms of patients with long COVID in France. The authors used data from the ComPaRe (Communauté de Patients pour la Recherche) long COVID cohort, an ongoing prospective e-cohort of patients with long COVID.

Long COVID patients were categorized in the vaccination cohort if they received a COVID-19 vaccine between the study baseline and 60 days, and non-vaccinated subjects were classified as controls. Propensity score matching was performed between the two cohorts, and patients were assessed at two intervals during the study, first at 60 days and the other at 120 days post inclusion in the study. Patients were asked to complete an online questionnaire at these intervals enquiring about the symptoms.

Patients reporting the persistence of symptoms had to undertake subsequent assessments with long COVID symptom (ST) and impact tools (IT), which examine the 53 known symptoms of long COVID and six dimensions of lives impacted by the disease.


The researchers analyzed data from about 910 adults who had a confirmed or suspected infection and reported persistence of COVID-19 symptoms after more than three months of illness with at least one symptom associated with long COVID. The median age of the subjects was 47 years, and a large proportion (80.5%) of them were females, and more than 60% had a confirmed history of COVID-19.

Half of the subjects were vaccinated with at least one dose of COVID-19 vaccines. Among the vaccinated, around 359 (78.9%) individuals received the BNT162b2 vaccine, 48 subjects injected with ChAdOx1 vaccine, 47 patients with the mRNA-1273 vaccine, and just one individual received Ad26.COV2.S vaccine.

About 16.6 and 7.5 % of patients, respectively, in the vaccination and control cohorts, had remission of all long COVID symptoms at 120 days after study baseline. The long COVID ST score was slightly higher in the control group (14.8) than in the vaccination cohort (13). The long COVID IT score was lower for vaccinated subjects (24.3) than controls (27.6), implying that the impact on patients' lives due to long COVID was significantly lower in the vaccination cohort than in the control group.

Twenty-six patients (5.7%) from the vaccination cohort reported adverse effects following vaccination, with two of them being hospitalized for deep vein thrombosis and meningitis. Some of them (2.8%) reported relapse of long COVID symptoms, and others (1 %) developed known vaccination-induced local and systemic reactions (pain at the site of injection, mild fever, etc.)


The authors reported that COVID-19 vaccination could reduce the severity of long COVID and its impact on patients' lives. With just two serious adverse effects of vaccination in long COVID patients, they suggested that SARS-CoV-2 vaccines are safe for these patients. The participants were infected with COVID-19 before May 2021, and thus, the study could not account for infections due to the SARS-CoV-2 Delta variant as the first case of Delta variant was reported in June 2021 in France.

 Moreover, the team postulated that long COVID might be due to any of the following three reasons: 1) persistent viral reservoir, 2) stimulation of immune system due to the presence of viral fragments, and 3) autoimmunity due to infection. Nonetheless, further research is required to investigate the exact mechanism of long COVID-19 and develop therapeutics and prophylactic measures for long COVID.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.


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