Journal of medical virologySep 10, 2026

Unique Immune Protein Patterns and Antibody Strength Separate Long COVID from Recovered Cases Despite Similar T Cell Responses

Updated Sep 11, 2026

Abstract

PASC patients had higher chronic comorbidities, hospitalization, and ICU admissions compared to recovered COVID-19 individuals.

Patients with post-acute sequelae of COVID-19 (PASC) experienced significant immune dysregulation, despite having similar levels of SARS-CoV-2-specific antibodies as recovered individuals.
Functional antibodies (neutralizing antibodies) were significantly higher in recovered COVID-19 individuals compared to those with PASC.
Interleukin-6 (IL-6) may serve as a useful biomarker for long-term inflammation in hospitalized PASC patients.
Higher levels of FGF-basic in hospitalized PASC patients suggest a link between elevated growth factor signaling and severity-related immune dysregulation.
The findings indicate that persistent symptoms in PASC may not be due to impaired antiviral immunity but rather to immune dysregulation.

Simplified

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.

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Unique Immune Protein Patterns and Antibody Strength Separate Long COVID from Recovered Cases Despite Similar T Cell Responses

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