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  1. Our take

    In a small study, available as a preprint and thus not yet peer-reviewed, of 66 COVID-19 patients with persistent COVID-19 symptoms 8 months after hospital discharge, receipt of at least one dose of Pfzier-BioNTech or AstraZeneca SARS-CoV-2 vaccinations was not significantly associated with symptom exacerbation or improvement. Findings, however, are subject to various limitations, including possible misclassification of symptom persistence in participants, a short observation period, and questionable generalizability to patients not requiring hospitalization during their acute COVID-19 infections.

    Study design


    Study population and setting

    Patients hospitalized for COVID-19 infections between April and May 2020 were recruited into a prospective cohort study measuring quality of life and recovery status at 3 and 8-month intervals from discharge date. Cohort participants who received at least one dose of the Pfizer-BioNTech or AstraZeneca SARS-CoV-2 vaccines in December 2020 were contacted one month later to assess symptom persistence, mental health, and quality of life. A control participant from the parent cohort study was matched to two vaccinated participants based on symptom persistence and quality of life measures 8 months post-hospitalization. Symptomatology and quality of life were compared in vaccinated participants and unvaccinated controls.

    Summary of main findings

    A total of 44 vaccinated patients were matched to 22 unvaccinated controls in the cohort study. Vaccinated patients were older (median age: 64 years) than unvaccinated control (median age: 55 years) and were more likely to have underlying health conditions, specifically heart (25% vs. 9.1%) and chronic lung (32% vs. 9.1%) diseases, respectively. A majority (82%) across both groups reported at least one persistent COVID-19 symptom 8 months after hospital discharge, the most common being fatigue (61%) and shortness of breath (50%). Eight months after hospital discharge, unvaccinated controls reported more persistent symptoms (median: 4.1 symptoms) per patient than vaccinated participants (median: 3.6 symptoms). Persistent COVID-19 symptoms remained unchanged in most vaccinated participants (70%) and unvaccinated controls (71%) 30 days after vaccination, irrespective of vaccine candidate received. Adjusting for participant age and gender, no significant differences in physical or mental health were observed 30 days after vaccination comparing vaccinated patients to unvaccinated controls.

    Study strengths

    Investigators matched vaccinated participants to unvaccinated controls on factors that would likely affect the observed association between vaccination status and physical mental health outcomes. Investigators also measured changes (improvement, maintenance, or aggravation) in individual symptoms in the one month after vaccination.


    While the investigators elicited information about changes in individual symptoms in the one-month period following vaccination, participants were discretely classified in regression analyses as having improved, unchanged, or exacerbated physical and mental health. As a result, outcomes may have been misclassified if, for example, some symptoms improved while others worsened over the observation period. Additionally, study participants included in the analytic cohort were followed for a median duration of 32 days; any changes in symptom persistence or severity beyond the observation period would not have been captured in the short follow-up window. Study procedures were also susceptible to response biases, as vaccinated participants may have been more likely to recall any changes in their symptoms since vaccination compared to unvaccinated controls. Inferences about the relationship between vaccination status and symptom persistence, aggravation, or attenuation are additionally limited by the study’s small sample size, resulting in low statistical power to detect differences between vaccinated participants and unvaccinated controls. Lastly, because the parent cohort included only adults with hospitalization history for COVID-19, results may not be generalizable to patients with persistent COVID-19 symptoms that did not require hospitalization during their acute infections.

    Value added

    This is among the first studies to assess safety and physiological responses to SARS-CoV-2 vaccines in patients with persistent symptoms from prior COVID-19 infections.

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