SEATTLE — U.S. veterans experience a high burden of COVID-19; characterizing immune responses associated with COVID-19 outcomes could help improve treatment of U.S. veterans, who experience a high burden of COVID-19, according to a recent study.
The authors from the VA Puget South Healthcare System in Seattle suggested that changes in peripheral blood cytokines over time might predict both acute outcomes and long COVID symptoms. VA researchers from Philadelphia and Palo Alto, CA, also participated in the study.
To find out, the study team quantified cytokine concentrations from peripheral blood collected 0-7 days (early) and 14-42 days (post-acute) after enrollment from SARS-CoV-2 positive participants in the EPIC3 study, a prospective, longitudinal cohort following U.S. veterans. Responses were correlated with Veterans Affairs Severity Index for COVID-19 criteria and chronic symptoms with the modified Medical Research Council Dyspnea scale, Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive function, and PROMIS Fatigue scores 3 months after enrollment (60-135 days).
In addition, in the study published in Frontiers in Immunology, trends in cytokine concentration with COVID-19 severity were assessed. The researchers estimated the odds of COVID-19 severity and long-term symptoms with logistic regression adjusted for sex, age and morbidity, also examining longitudinal changes in cytokine concentration for participants sampled during both time periods, by severity and long-term symptom group.
The results indicated that early HGF, IL-18, IL-1RA, IP-10, and VEGF-A and post-acute MIP-1α and VEGF-A concentrations trended positively with increasing COVID-19 severity (q-values < 0.05, Jonckheere-Terpstra trend test). The authors found that increases in EGF, MIP-1β and RANTES concentration and decreases in MIP-1α concentration over time were associated with mild rather than moderate or severe disease, while increases in MIP-1β and RANTES concentration and decreases in Eotaxin concentration over time were associated with the absence of long-term symptoms.
“Worse COVID-19 severity by 30 days was associated with higher early and post-acute period cytokine concentrations,” the researchers wrote. “Participants with long-term symptoms did not see resolution of cytokine responses over time.”
- Mendall C, Li X, Pakanati V, Liu C, et. al. Peripheral blood cytokines during early and post-acute stages of SARS-CoV-2 infection are associated with disease severity and long-term symptoms. Front Immunol. 2026 Jul 15;17:1870109. doi: 10.3389/fimmu.2026.1870109. PMID: 42528778; PMCID: PMC13415590.
