OPG and BAFF as predictive biomarkers of the severity of SARS-CoV-2 infection

Molecules of the tumour necrosis factor superfamily (TNFSF) are key players in immune regulation; an increase in some TNFSF molecules has been reported during severe COVID-19. In this study, we profiled and evaluated TNFSF members in the serum of COVID-19 vaccine-naïve patients to identify potential biomarkers associated with disease severity. Our data show that TRAIL serum levels are lower in severely affected patients than those mildly affected by COVID-19 (AUC 0.8, p = 0.0003). On the contrary, OPG and BAFF serum levels are higher in severe COVID-19 compared to mild COVID-19 cases (AUC 0.8, p = 0.0001; AUC 0.7, p = 0.0012; respectively) and moderate COVID-19 cases (OPG p < 0.01), BAFF (p < 0.05). At the transcriptional level, TRAIL, OPG and BAFF are elevated in severe compared to mild COVID-19 cases, with OPG and BAFF also higher in moderate compared to mild COVID-19 patients. Additionally, we found that APRIL, LIGHT, CD30L and CD40L protein-levels are higher in COVID-19 patients compared to healthy donors but not significantly different between various COVID-19 clinical statuses. Finally, we found that TNF-α, TNF-β, RANKL and TWEAK protein levels were not affected during COVID-19. Our work identifies OPG and BAFF as potential biomarkers and therapeutic targets for preventing severe COVID-19. Due to the opposite contradictory levels of TRAIL (protein/transcriptional level), its role during COVID-19 should be elucidated and clarified with more in-depth studies.