tetano
Editor, Senior Moderator
Front Immunol
. 2026 Jul 15:17:1870109.
doi: 10.3389/fimmu.2026.1870109. eCollection 2026.
Peripheral blood cytokines during early and post-acute stages of SARS-CoV-2 infection are associated with disease severity and long-term symptoms
Calen Mendall[SUP] 1 2 [/SUP], Xumin Li[SUP] 1 2 [/SUP], Vivek Pakanati[SUP] 1 [/SUP], Cindy Liu[SUP] 1 [/SUP], Tracy Wang[SUP] 1 [/SUP], Daniel Morelli[SUP] 1 [/SUP], Anna Korpak[SUP] 1 [/SUP], Aaron Baraff[SUP] 1 [/SUP], Stuart N Isaacs[SUP] 3 4 [/SUP], Kyong-Mi Chang[SUP] 3 4 [/SUP], Elizabeth Le[SUP] 5 [/SUP], Mark Holodniy[SUP] 5 [/SUP], Jonathan D Sugimoto[SUP] 2 6 [/SUP], Nicholas L Smith[SUP] 1 2 [/SUP], Jennifer S Lee[SUP] 5 7 [/SUP], Jennifer M Ross[SUP] 1 8 [/SUP], Javeed A Shah[SUP] 1 8 [/SUP]
Affiliations
Background: U.S. Veterans experience a high burden of COVID-19; characterizing immune responses associated with COVID-19 outcomes could help improve treatment. Changes in peripheral blood cytokines over time may predict both acute outcomes and long COVID symptoms.
Methods: Cytokine concentrations were quantified from peripheral blood collected 0-7 days (early) and 14-42 days (post-acute) after enrollment from SARS-CoV-2 positive participants in the EPIC[SUP]3[/SUP] 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). Trends in cytokine concentration with COVID-19 severity were assessed. Odds of COVID-19 severity and long-term symptoms were estimated with logistic regression adjusted for sex, age, and morbidity. Longitudinal changes in cytokine concentration were examined for participants sampled during both time periods, by severity and long-term symptom group.
Results: 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). 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. Increases in MIP-1β and RANTES concentration and decreases in Eotaxin concentration over time were associated with the absence of long-term symptoms.
Conclusions: Worse COVID-19 severity by 30 days was associated with higher early and post-acute period cytokine concentrations. Participants with long-term symptoms did not see resolution of cytokine responses over time.
Keywords: COVID-19; SARS-CoV-2; U.S. veterans; cytokines; long Covid.
. 2026 Jul 15:17:1870109.
doi: 10.3389/fimmu.2026.1870109. eCollection 2026.
Peripheral blood cytokines during early and post-acute stages of SARS-CoV-2 infection are associated with disease severity and long-term symptoms
Calen Mendall[SUP] 1 2 [/SUP], Xumin Li[SUP] 1 2 [/SUP], Vivek Pakanati[SUP] 1 [/SUP], Cindy Liu[SUP] 1 [/SUP], Tracy Wang[SUP] 1 [/SUP], Daniel Morelli[SUP] 1 [/SUP], Anna Korpak[SUP] 1 [/SUP], Aaron Baraff[SUP] 1 [/SUP], Stuart N Isaacs[SUP] 3 4 [/SUP], Kyong-Mi Chang[SUP] 3 4 [/SUP], Elizabeth Le[SUP] 5 [/SUP], Mark Holodniy[SUP] 5 [/SUP], Jonathan D Sugimoto[SUP] 2 6 [/SUP], Nicholas L Smith[SUP] 1 2 [/SUP], Jennifer S Lee[SUP] 5 7 [/SUP], Jennifer M Ross[SUP] 1 8 [/SUP], Javeed A Shah[SUP] 1 8 [/SUP]
Affiliations
- PMID: 42528778
- PMCID: PMC13415590
- DOI: 10.3389/fimmu.2026.1870109
Background: U.S. Veterans experience a high burden of COVID-19; characterizing immune responses associated with COVID-19 outcomes could help improve treatment. Changes in peripheral blood cytokines over time may predict both acute outcomes and long COVID symptoms.
Methods: Cytokine concentrations were quantified from peripheral blood collected 0-7 days (early) and 14-42 days (post-acute) after enrollment from SARS-CoV-2 positive participants in the EPIC[SUP]3[/SUP] 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). Trends in cytokine concentration with COVID-19 severity were assessed. Odds of COVID-19 severity and long-term symptoms were estimated with logistic regression adjusted for sex, age, and morbidity. Longitudinal changes in cytokine concentration were examined for participants sampled during both time periods, by severity and long-term symptom group.
Results: 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). 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. Increases in MIP-1β and RANTES concentration and decreases in Eotaxin concentration over time were associated with the absence of long-term symptoms.
Conclusions: Worse COVID-19 severity by 30 days was associated with higher early and post-acute period cytokine concentrations. Participants with long-term symptoms did not see resolution of cytokine responses over time.
Keywords: COVID-19; SARS-CoV-2; U.S. veterans; cytokines; long Covid.