Study shows vaccine reduces long-term COVID risk, especially for people with pre-existing conditions

A recent study published in the journal JAMA Network Open, The researchers conducted a prospective cohort study to investigate at-risk populations and factors associated with extended time to recovery after COVID-19 infection. In particular, they evaluated risk factors contributing to recovery taking longer than 90 days (“long COVID”). Findings from a dataset of 4,708 participants revealed that women and adults with suboptimal pre-pandemic health (especially pre-existing cardiovascular disease) were more likely to suffer from long COVID. It is gratifying to observe that vaccination before and during the wave of the Omicron variant reduces these risks.

study: Epidemiological characteristics of recoveries from SARS-CoV-2 infectionImage credit: p.ill.i / Shutterstock

Current knowledge about Long COVID and the role of vaccination

The US Centers for Disease Control and Prevention (CDC) defines long COVID as “a chronic illness that develops after SARS-CoV-2 infection and lasts for at least 3 months.” It is characterized by the persistence of coronavirus disease 2019 (COVID-19) symptoms, sometimes even after recovery from and discharge from the hospital from the initial COVID-19 infection. The so-called post-COVID-19 condition (PCC), which affects one in five COVID-19 survivors (about 20%), is a major public health concern due to its debilitating effects on patients and their families.

Unfortunately, given the relatively new nature of the disease, research findings on the disease (especially epidemiology) are often confusing. This is likely due to substantial differences in sample collection methods, outcome definitions, and causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. It is now almost universally accepted that vaccination has controlled the pandemic and potentially saved millions of lives, but its impact on survivors and the risk of developing long COVID are equally confusing. Some reports highlight a risk-suppressing effect, others show no such association, and still others suggest that it may contribute to an increased risk of long COVID.

A notable limitation of most of the literature on long COVID is that they rely on electronic health records, some of which lack pre-pandemic health data. Because of this, these studies are unable to take into account pre-existing health conditions that may exacerbate COVID-19 infection and contribute to the subsequent development of PCC in COVID-19 survivors.

About the Research

In this report, researchers conducted a prospective cohort study including epidemiological data from 14 US-based longitudinal cohort studies. Unlike previous literature that utilized electronic health records of hospital- or laboratory-confirmed COVID-19 survivors, this study also included data on home-diagnosed SARS-CoV-2 infections, provided that patients' pre-existing clinical conditions were systematically recorded. Methodology and study findings were reported according to the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Data for this study were obtained from the Collaborative Cohort for COVID-19 Research (C4R), a metacohort funded by the National Institutes of Health. This metacohort consists of 14 established prospective cohorts with data dating back to 1971. Inclusion criteria for this study were COVID-19 survivors who were alive as of March 1, 2020 and available for follow-up, with follow-up occurring between April 2020 and March 2023. Data were collected using a questionnaire survey administered twice to eligible participants via telephone or face-to-face interviews or email questionnaires.

Data of interest include pre-existing medical conditions (particularly diabetes, hypertension, asthma and chronic obstructive pulmonary disease). [COPD]cardiovascular disease [CVD]), COVID-19 infection duration (COVID-19 pandemic wave), infection severity, and vaccination status as confirmed by vaccination report. Additionally, race/ethnicity, anthropometric and socio-demographic data were included as confounders (including smoking status, alcoholism). Recovery after COVID-19 was verified using a questionnaire, which, after a positive answer, asked about duration of COVID-19 or long COVID, if applicable.

Statistical analyses consisted of Kaplan-Meier curves to estimate time-dependent probability of recovery (> or < 90 days) and restricted mean recovery times. To assess differences in recovery times between subcohorts (e.g., different ethnicities), the log-rank test was used.

“Cox proportional hazards regression analyses were performed to assess multivariate-adjusted associations with recovery within 90 days. All factors were included in the fully adjusted models, with two exceptions. Severity of acute infection was only included in sensitivity analyses, as it was hypothesized to act as a mediating factor.”

Secondary analyses included recalculation of Cox proportional hazards models considering type and number of mRNA vaccinations, and vaccination status as variables.

Findings and Conclusions

Of 53,143 eligible participants in C4R, only 4,708 completed both follow-up surveys and were included in the current analysis. The mean age of participants was 61.3 years, and 62.7% of participants were women. According to infection severity records, 12.6% (597) of participants required hospitalization and 3.1% (148) required intensive care. 966 (20.5%) participants had received a vaccination prior to infection, but 5.9% (57) had received only one dose.

“The median time to recovery was 20 days (IQR, 8-75 days) and decreased over time. Participants who were vaccinated at the time of infection had a shorter median time to recovery. The probability of not recovering at 90 days was 22.5% (95% CI, 21.2%-23.7%) and differed between the pre-Omicron wave (23.3%; 95% CI, 22.0%-24.6%) and the Omicron wave (16.8%; 95% CI, 13.3%-20.2%).”

The analysis revealed that women took longer to recover from COVID-19 infection (average 42.3 days) than men (average 31.5 days). Participants with pre-existing medical conditions, especially CVD, were more likely to report not having recovered after 90 days compared to healthy individuals. It is reassuring that vaccination prior to infection was associated with both a reduced risk of acute infection and a reduced risk of long-term COVID-19 morbidity, mainly with multiple vaccine doses, even in women and individuals with pre-existing CVD.

In summary, the report reveals that one in five COVID-19 survivors (approximately 20%) develop long COVID, with women and adults with pre-existing health conditions at highest risk. It highlights the benefit of vaccination, especially multiple doses, in reducing this risk, especially during the Omicron wave.

“Further investigations into the long-term prognosis and mechanisms of PCC, including comparisons of the structure and function of multiple organs before and after infection, will be important to inform treatment and prevention.”