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J Med Virol . Distinct Cytokine Signatures and Antibody Neutralization Capacity Differentiate Post-Acute Sequelae of COVID-19 From Recovered Individua

tetano

Editor, Senior Moderator
J Med Virol

. 2026 Sep;98(9):e71145.
doi: 10.1002/jmv.71145.

Distinct Cytokine Signatures and Antibody Neutralization Capacity Differentiate Post-Acute Sequelae of COVID-19 From Recovered Individuals Despite Comparable T Cell Responses​


P R Sreelakshmi 1 , Priyanka Wagh 2 , Prakash Sarje 2 , Tanvi Shinde 2 , P Anisha 2 , Rahul Jagtap 2 , Sachin Dhaigude 2 , Babasaheb V Tandale 1 , Anuradha S Tripathy 2

Affiliations Expand


Abstract​


High prevalence of post-acute sequelae of COVID-19 (PASC/long COVID) has led to the determination of the pathophysiology of PASC. In a hospital-based cross-sectional survey, we assessed the clinical and immunological parameters in a set of 67 PASC and 81 recovered individuals from COVID-19 (N-PASC), to identify the immune biomarkers associated with the mechanistic cornerstone of this condition. PASC had higher chronic comorbidities, hospitalization, and ICU admissions during the COVID-19 pandemic compared to the N-PASC group. Though comparable SARS-CoV-2-specific antibodies were detected across the groups, their functionality (NAbs) was significantly higher in the N-PASC. PASC patients exhibited features of immune dysregulation, characterized by altered coordination between cellular and humoral immune responses despite broadly comparable cytokine profiles and T-cell responses. ROC analysis in hospitalized PASC and hospitalized N-PASC subjects sampled at 1, 2, and 3 years post COVID-19 supported the utility of IL-6 as a biomarker for long-term inflammatory activity. Higher FGF-basic levels in the hospitalized PASC compared to non-hospitalized PASC highlighted a potential association between elevated growth factor signaling and severity-related immune dysregulation, tissue damage that may have utility as a biomarker candidate. Our analysis supports a dysregulated crosstalk between humoral and cellular immunity in PASC patients, which could be leading to inflammation and persistent clinical symptoms associated with this debilitating condition. In conclusion, comparable T-cell and cytokine responses among long COVID and recovered individuals suggest that persistent symptoms are unlikely to be driven by impaired antiviral immunity, underscoring the potential role of immune dysregulation.

Keywords: IL‐6 and FGF‐Basic; IgG and NAbs; T cell response; immune dysfunction; post‐acute sequelae of COVID‐19.
 
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