The Journal of infectious diseasesOct 22, 2021

Signs of Immune Activation and Inflammation in People with Long-Term Effects After Severe COVID-19 Infection

Updated Jan 13, 2026

Abstract

During early recovery, those who developed PASC had 1.14-fold higher levels of tumor necrosis factor-α compared to those without PASC.

Higher levels of cytokine biomarkers were observed in individuals who later developed postacute sequelae of COVID-19 (PASC).
Interferon-γ-induced protein 10 levels were 1.28-fold higher in early recovery among those who went on to develop PASC.
A trend toward increased interleukin 6 levels was noted during early recovery for those with PASC, which became more significant in late recovery.
In late recovery, interleukin 6 levels were 1.44-fold higher among those with PASC symptoms compared to those without.
These findings suggest that persistent immune activation may be linked to ongoing symptoms after COVID-19.

Simplified

BACKGROUND: The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown.

METHODS: We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods.

RESULTS: During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P < .001). These differences were more pronounced among those with a greater number of PASC symptoms.

CONCLUSIONS: Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.

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Signs of Immune Activation and Inflammation in People with Long-Term Effects After Severe COVID-19 Infection

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