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New Data Reveal How COVID-19 Vaccination Can Decrease Severity, Mortality Following SARS-CoV-2 Infection


Immunization Awareness Month

Findings from a new study show the long-term benefits of COVID-19 vaccination to reduce inflammation after a breakthrough infection, say researchers.

New Data Reveal How COVID-19 Vaccination Can Decrease Severity, Mortality Following SARS-CoV-2 Infection / Image credit: ©jasniulak/AdobeStock


New research sheds light on whether COVID-19 vaccinations reduce disease severity and mortality following SARS-CoV-2 infection.1

Findings published August 7, 2023, in The Lancet Microbe showed that among persons recently infected with SARS-CoV-2, those who were fully vaccinated had lower concentrations of nearly all inflammatory markers (cytokines and chemokines) than those who were unvaccinated in the short-term and long-term after symptomatic SARS-CoV-2 infection.1

“Our research demonstrates the long-term benefits of the COVID-19 vaccines to reduce inflammation even after a breakthrough infection,” said coauthor Alison Abraham, PhD, MS, MHS, associate professor of epidemiology at the Colorado School of Public Health on the University of Colorado Anschutz Medical Campus, in a press release. “Understanding how to prevent long-term complications and death with COVID-19 and how vaccination prevents those outcomes is critically important to opening doors for more targeted therapy for those who get severe disease.”2

According to Abraham and colleagues, the study is one of the first to examine the effect of COVID-19 vaccination on longitudinal cytokine and chemokine concentrations and trajectories among persons recently infected with SARS-CoV-2.1

To do this, researchers collected blood samples from participants aged ≥18 years enrolled in a clinical trial that examined the efficacy of convalescent plasma therapy for ambulatory COVID-19 in 23 outpatient sites across the US, according to the study.1

In the current study, participants were limited to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening, day 14, and day 90 visits. Investigators analyzed the associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) using multivariate linear mixed-effects regression models that were adjusted for age, sex, body mass index, hypertension, diabetes, convalescent or control plasma, and COVID-19 waves (prealpha or alpha and delta).1

“Unlocking the why, when and how the cytokine storm produced by SARS-CoV-2 will mean improved control over how we care for patients and develop treatments,” said senior author Aaron Tobian, MD, PhD, professor of pathology, medicine, and epidemiology at the Johns Hopkins University School of Medicine in the press release. “In other words, answering how the COVID-19 vaccine works to prevent worse disease, longer term disease and death can help us better treat patients by providing solutions to limit the body’s overexuberant inflammatory response.”2


Overall, 882 participants were enrolled in the study between June 29, 2020, and September 30, 2021, of whom 57% were women, 78% were unvaccinated, 6% were partly vaccinated, and 16% were fully vaccinated at baseline. Among the unvaccinated group, 37% were aged ≥50 years and 21% of the fully vaccinated group were aged ≥50 years.1

After adjusting for confounders, researchers observed that geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumor necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening.1

At day 90, fully vaccinated persons had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Also, results showed that cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups as well as in the unvaccinated group.1

“Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days,” added Tobian and colleagues.1

Investigators also noted that days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations.1

“These findings suggest that vaccination might have short-term and long-term benefits after symptomatic infection and indicates a mechanistic explanation for the significantly reduced disease severity and mortality among vaccinated cohorts,” wrote researchers. “Thus, it is essential to raise public awareness of the benefits of vaccination and guarantee equitable distribution of vaccines globally.”1


1. Abraham A, Tobian A, Zhu X, et al. Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: A prospective cohort study. The Lancet Microbe. Published online August 7, 2023. doi:10.1016/S2666-5247(23)00171-4.

2. Julia Milzer. New Research Shines Light on How COVID-19 Vaccination Reduces Severity and Mortality After Breakthrough Infections. News release. Published August 8, 2023. Accessed August 9, 2023. https://news.cuanschutz.edu/news-stories/new-research-shines-light-on-how-covid-19-vaccination-reduces-severity-and-mortality-after-breakthrough-infections

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