Immune Dysregulation After COVID-19: Longitudinal Analysis up to 9 Months

Journal article

SARS-CoV-2 infection triggers a strong inflammatory response, and persistent symptoms after recovery are thought to reflect prolonged systemic dysregulation. However, mechanisms underlying long COVID remain unclear. This study evaluated longitudinal changes in cytokine hematological and biochemical parameters up to nine months after hospitalization for COVID-19 and examined their relationship with persistent symptoms, vaccination status, and the occurrence of comorbidities. Long COVID patients showed sustained elevations in IL-2, IL-6, IL-10, IL-17A, CXCL9, TNF-α, and IFN-γ compared with healthy controls, exhibiting heterogeneous temporal trajectories. Specifically, levels of IL-2, IL-10, TNF-α, and creatinine continued to increase over time, whereas IFN-γ, LDH, CCL2, CXCL9, and CXCL10 declined. Other parameters exhibited greater variability without a uniform longitudinal pattern. IL-6 demonstrated consistently high diagnostic performance in distinguishing individuals after COVID-19 from healthy controls (AUC > 0.82). Aging substantially affects cytokine profiles and systemic inflammatory status; therefore, residual age-related confounding cannot be fully excluded despite statistical adjustment. Although symptoms such as fatigue, cough, and dyspnea were still reported at nine months, no stable associations were identified between cytokine concentrations and clinical manifestations. These findings indicate that while immune alterations persist long after acute infection, systemic cytokine measurements alone may be insufficient to explain the presence or persistence of symptoms. The results suggest that long COVID reflects multifactorial processes extending beyond systemic inflammation and highlight the need for further research into mechanisms driving long-term long COVID sequelae.

Authors: Mitkowski, P; Leśniak, M; Kobza, D; Aleksandrowicz, K; Chodowiec, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: International Journal of Molecular Sciences
• Volume: 27
• Issue: 11
• Pages: 5137
• Publication date: 2026-06-05
• DOI: 10.3390/ijms27115137
• EISSN: 1422-0067
• ISSN: 1661-6596
• Pmid: 42278658
• Language: English
• Keywords: Female; SARS-CoV-2; Covid-19; Cytokine Storm; Male; Middle Aged; Longitudinal Studies; Humans; Aged; Post-Acute COVID-19 Syndrome; Disease severity; Biomarkers; Immune Dysregulation; Cytokines; COVID-19