OPG and TNFR1 as Potential Biomarkers of Inflammation in Older Adults with Acute COVID-19 and Indicators of Frailty in Post-COVID-19: A Pilot Study

Lucero A Ramon-Luing,1,* Julio Flores-Gonzalez,1,* Daniela Josefina Cataneo-Piña,2 Ramcés Falfán-Valencia,1 Gloria Pérez-Rubio,1 Ivette Buendia-Roldan,1 Moisés Selman,1 Leslie Chavez-Galan1 1Research Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico; 2Geriatrics, Palliative Care Clinic, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico*These authors contributed equally to this workCorrespondence: Leslie Chavez-Galan, Laboratorio de Inmunología Integrativa, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City, 14080, Mexico, Tel +525554871700 ext. 5270, Email [email protected]; [email protected]: Older individuals are at high risk for severe COVID-19 and often experience geriatric syndromes as post-COVID-19 sequelae associated with inflammation. Osteoprotegerin (OPG) and Tumor Necrosis Factor Receptor 1 (TNFR1) are emerging as promising biomarkers in inflammation-associated diseases. Here, these and other members of the tumor necrosis factor superfamily (TNFSF) were investigated as potential biomarkers to monitor older adults during acute COVID-19 and post-COVID-19 recovery.Patients and Methods: This study included 75 patients with acute COVID-19, 26 post-COVID-19 (evaluated at 4 and 12 months), 35 healthy donors (HD), and 36 individuals with interstitial lung diseases (ILD), all aged over 60. Plasma levels of 14 soluble TNFSF members were measured using flow cytometry-based multiplex immunoassays and ELISA. Multiple logistic regression and ROC curve analyses were performed to assess the potential of TNFSF members as biomarkers.Results: Flow cytometry revealed significantly higher levels of OPG, BAFF, and APRIL in acute COVID-19 patients than in HD and ILD (p< 0.001). Through an ELISA, high levels of OPG (p< 0.0001), APRIL (p< 0.05), and BAFF (p< 0.0001) were confirmed, and TNFR1 (p< 0.0001) was also revealed. In this pilot study, OPG and TNFR1 had AUCs > 0.90 and were predictive of COVID-19, independent of comorbidities, while BAFF levels were modified by diabetes. Persistently elevated OPG and TNFR1 levels were also observed in post-COVID-19 patients at 4 and 12 months. Notably, OPG levels were higher in frail versus non-frail individuals at both time points (p< 0.05), while TNFR1 levels were higher only at 4 months (p< 0.05).Conclusion: This evidence indicates that OPG and TNFR1 are potential biomarkers of inflammation during acute COVID-19 and post-COVID-19 among older, mainly frail adults. These findings support their utility in managing post-COVID-19 geriatric frailty syndrome.Keywords: SARS-CoV-2, aging, TNFSF, inflammaging, immunosenescence, frailty, biomarker