Markers of immune activation and inflammation in individuals with post-acute sequelae of SARS-CoV-2 infection

• Published in: Antiviral therapy 2021-12, Vol.26, p.1
• Main Authors: Peluso, M, Lu, S, Tang, A, Durstenfeld, M S, Ho, H, Goldberg, S A, man, C A, Munter, S E, Hoh, R, Tai, V, Chenna, A, Yee, B C, Winslow, J W, Petropoulos, C J, Greenhouse, B, Hunt, P W, Hsue, P Y, Martin, J N, Kelly, J D, Glidden, D V, Deeks, S G, Henrich, T J
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Body mass index; Complications; Coronaviruses; COVID-19; Immune response; Infections; Inflammation; Interleukin 10; Interleukin 6; IP-10 protein; Monocyte chemoattractant protein 1; Severe acute respiratory syndrome coronavirus 2; Therapeutic targets; Tumor necrosis factor; γ-Interferon
• ISSN: 1359-6535; 2040-2058

Objectives/aim: The biological processes associated with post-acute sequelae of SARS-CoV-2 infection (PASC) are unknown. We aimed to characterize markers of immune activation in a cohort of individuals with PASC at >90 days following COVID-19 symptom onset. Methods: Using the highly sensitive Simoa immunoassay platform, we measured soluble markers of inflammation (TNF-alpha, IL-6, IL-10, MCP-1, IP-10, IFN-gamma) and antibodies against the SARS-CoV-2 receptor binding domain (RBD) in the San Francisco-based Long-term Impact of Infection with Novel Coronavirus (LIINC) SARS-CoV-2 recovery cohort at early recovery (90 days) timepoints. These analytes were selected based on their relevance in acute COVID-19. All individuals (n=121) had prior SARS-CoV-2 infection confirmed with nucleic acid amplification testing, were recruited through clinician or self-referral, and completed detailed symptom questionnaires during recovery. We defined PASC as the presence of one or more COVID-19-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with (n=48) and without (n=73) 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 TNF-alpha (1.14-fold higher mean ratio, 95% CI 1.01, 1.28; P=0.028) and IP-10 (1.28-fold higher mean ratio, 95% CI 1.01, 1.62; P=0.038). Among those with PASC, there was a trend toward higher IL-6 levels during early recovery (1.28-fold higher mean ratio, 95% CI 0.98-1.70; P=0.07) which became more pronounced in late recovery (1.44-fold higher mean ratio, 95% CI: 1.11, 1.86; P