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Reduced Incidence of Long-COVID Symptoms Related to Administration of COVID-19 Vaccines Both Before COVID-19 Diagnosis and Up to 12 Weeks After

Our take —

This preprint, which has yet to be peer reviewed, retrospectively examined 240,648 individuals in the US who were diagnosed with COVID-19 before May 31, 2021 and evaluated the effectiveness of COVID-19 vaccination both before and up to 12 weeks after diagnosis on preventing the occurrence of long COVID associated illness or symptoms as defined by COVID-19 interoperability alliance. 12-20 weeks following acute COVID-19 diagnosis. Most individuals in the study (91.6%) were unvaccinated within 12 weeks after their COVID-19 diagnosis, 7.4% (17796) were vaccinated within 12 weeks of their diagnosis and only 1% (2392) were vaccinated prior their diagnosis. Compared to unvaccinated individuals, the authors observed a protective effect of COVID-19 vaccination in reducing the likelihood of long COVID-19 continuing symptoms occurring within 12 to 20 weeks following diagnosis, with a greater reduction in odds with shorter durations of vaccination after COVID-19 diagnosis. On the other hand, those who were vaccinated prior to their diagnosis had the lowest risk of experiencing long COVID-19 12-20 weeks after diagnosis (OR: 0.22, 95%CI 0.196-0.245). Although the authors relied on sets of symptoms and conditions that have not been fully validated as associated with long COVID, this study provides additional evidence that vaccination provides some protection against the occurrence of clinical symptoms associated with long COVID 12-20 weeks following diagnosis. 

Study design

Retrospective Cohort

Study population and setting

This retrospective cohort study evaluated the role of vaccination (Pfizer, Moderna, and Johnson and Johnson) on reducing the likelihood of experiencing long COVID-19 symptoms, defined as the presence of at least one COVID-19-associated symptom (fever, loss of taste or smell, etc) between 12 and 20 weeks after initial diagnosis. The study used the Arcadia Data Research Database to identify individuals in the U.S. who had SARS-CoV-2 infection at least 20 weeks before May 21, 2021, the deadline for data extraction. Individuals had to have had at least one health care visit before and after Jan 1, 2020.  The primary exposure of interest was timing of the first dose of a COVID vaccine relative to the date of COVID-19 diagnosis: prior to diagnosis, 0-4 weeks, 4-8 weeks, 8-12 weeks, and more than 12 weeks post-diagnosis, with unvaccinated as the reference group. The outcome was defined as the occurrence of at least one or an aggregate of COVID-19-associated symptoms 12-20 weeks after diagnosis. The following additional covariates were collected for each individual: age, sex, race, ethnicity, insurance type, and comorbid conditions prior to COVID-19 diagnosis. Multiple logistic regression models were used to estimate the association between vaccination timing and the presence of any long COVID-19 symptom. Sensitivity analyses examined the association between timing of vaccination as a continuous metric with a count of the number of long-COVID symptoms 12 weeks post-diagnosis. 

Summary of Main Findings

Between Feb 2020 and May 2021, 240,648 individuals were diagnosed with COVID-19 and had at least one primary care visit both before January 1, 2020 and at least 20 weeks after their diagnosis. Of these, 91.6% (n=220,460) hadn’t received the first dose of a COVID-19 vaccine 12 weeks after their COVID-19 diagnosis, while 17.4% (n=17,796) were vaccinated within 12 weeks and 1% (n=2,392) were vaccinated prior to their COVID-19 diagnosis. Patients vaccinated before a COVID-19 diagnosis were 78% less likely to have any long COVID symptoms than unvaccinated individuals (OR: 0.22, 95%CI 0.196-0.245). Previously unvaccinated individuals who were vaccinated 0-4 weeks, 4-8 weeks, and 8-12 weeks after their COVID-19 diagnosis also had reduced odds of reporting any long COVID-19 symptoms compared to unvaccinated individuals (OR: 0.382, 95%CI 0.353-0.413; OR: 0.535, 95%CI 0.506-0.567; and OR: 0.747,95%CI 0.713-0.784 respectively). 

Study Strengths

This study used an extensive, broadly-representative database to assess the effectiveness of the timing of COVID-19 vaccination on preventing long-COVID symptoms 12-20 weeks after diagnosis. 


Only 7.4% of the total study cohort had any vaccination within 12 weeks after their date of COVID-19 diagnosis. The authors did not consider potential confounding by other notable confounding variables such as pre-existing co-morbidities, which may contribute to the likelihood of COVID-19 symptoms and may be differentially distributed across vaccinated and unvaccinated individuals. Extrapolation, inaccurate inference, and residual confounding could have occurred if there is a big difference in the distribution of the confounding variables among these groups. Finally, no distinction was made between the 3 major COVID-19 vaccines available in the US. 

Value added

The study was one of the larger, broadly-representative study suggesting a protective effect of vaccination with either Pfizer, Moderna, or Johnson and Johnson on preventing long COVID-19 symptoms. 

This review was posted on: 5 January 2022