What is the impact of pre-COVID vaccination on long COVID?

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to impact people's lives globally even after two years. The World Health Organization (WHO) has reported over 617 million confirmed cases and more than 6.5 million deaths associated with COVID-19 worldwide.

Study: Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program. Image Credit: eamesBot/Shutterstock
Study: Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program. Image Credit: eamesBot/Shutterstock

Several studies have indicated the occurrence of post-acute sequelae of SARS-CoV-2 infection (PASC) weeks after SARS-CoV-2 infection. Long COVID is the broad term used to define the ever-shifting symptoms of PASC.


Most studies have observed vaccines to be effective and safe at reducing the risk of severe COVID-19. However, their impact on long COVID is not fully understood. Some studies indicate vaccines have a protective effect, while others report mixed or anti-protective effects.

A new study posted to the pre-print server medRxiv* aimed to analyze the impact of pre-COVID-19 vaccination on long COVID diagnosis.

About the study

The study was a part of the National Institutes of Health (NIH) that developed the RECOVER initiative to treat, understand, and prevent PASC. All the analyses in the study were performed within the National COVID Cohort Collaborative (N3C) enclave that used electronic health records (EHRs) to obtain patient data. A COVID-19 index date was determined per the earliest indication of COVID-19 infection.

The inclusion criteria to be eligible for the study included having either an International Classification of Diseases-10-Clinical Modification (ICD-10) COVID-19 diagnosis code or a SARS-CoV-2 antigen or PCR test along with a recorded health care visit between 120 and 300 days following index, having either completed vaccination status or not started vaccine regimen at index, being 18 years and older at index, and having at least two recorded health care visits in the year before the index.

Moreover, the vaccination coverage at each healthcare site was calculated through the ratio of the observed proportion of patients with a vaccination record and the expected rate of vaccination obtained from CDC reporting. Only those sites where the observed proportion was at least two-thirds of their expected vaccination rate were included in the study.

Individuals who completed their vaccination regime before the index were considered vaccinated, while others were considered unvaccinated. Three indicators were considered for long COVID: an ICD-10 code for post-COVID-19 condition (U09.9), a visit to a long COVID clinic, and an ICD-10 code for outcomes of other parasitic and infectious diseases (B94.8). Finally, a model was used to calculate the long COVID score for each patient that ranged from 0 to 1, with patients scoring above 0.9 labeled as having long COVID.

Study findings

The results indicated a protective association between long COVID and vaccination status in model- and clinic-based cohorts. The protective association was observed to remain consistent among those who contracted COVID-19 during a later period, as well as those who required a clinical diagnosis.

Also, individuals with a model score of 0.6 to 0.9 were observed to show some symptoms of long COVID.

Therefore, the current study demonstrates that vaccination is an important tool for combating COVID-19. Pre-COVID vaccination was observed to retain a protective effect against long COVID, even for breakthrough infections.


The study has certain limitations. First, the study relies on EHRs and other factors, which might not be completely accurate. Second, the study did not differentiate between vaccine types. Third, the implementation of the ICD10 code, U09.9 did not take place until October 2021. Finally, the model-based cohort might comprise misclassification of long COVID outcomes.

*Important notice

medRxiv 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:
Suchandrima Bhowmik

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.


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