Fig 2: APRIL, LIGHT, CD30L and CD40L are elevated in sera from COVID‐19 patients. APRIL, LIGHT, CD30L, CD40L and FasL (A–E, respectively) levels were evaluated in sera of healthy donors (HD) (n = 30) and COVID‐19 patients (n = 98) by LEGENDplexTM. Data are presented as mean +/− SD (red); each symbol represents an individual subject. Statistical analysis was performed using the Mann–Whitney U test to compare the two groups. ****p < 0.0001, **p < 0.01 and *p < 0.05.

Fig 3: Systemic levels of OPG and BAFF are increased in severe COVID‐19 cases. OPG and BAFF levels were evaluated in sera of healthy donors (HD) and COVID‐19 patients by LEGENDplex™. OPG levels were compared between HD (n = 30) and COVID‐19 (n = 98) (A) and among mildly (n = 32), moderately (n = 29) and severely (n = 37) COVID‐19 affected patients (B). Similarly, BAFF levels between HD (n = 30) and COVID‐19 (n = 98) cases were compared (D). BAFF levels were also compared among mild (n = 32), moderate (n = 29) and severe (n = 37) COVID‐19 cases (E), where the dotted green line indicates the mean HD value. Data are presented as mean +/− SD (red); each symbol represents an individual subject. The receiver operating characteristics (ROC) curves show the area under the curve (AUC) identified by comparing mild (dotted red line) and severe cases (grey dot); then, the sensitivity, specificity and cut‐off value (pg/mL) were obtained for OPG (C) and BAFF (F). Statistical analysis was performed with the Mann–Whitney U test to compare two groups (A and D) or the Kruskal–Wallis test and corrected using Dunn's test to compare groups (B and E). ****p < 0.0001, ***p < 0.001, **p < 0.01 and *p < 0.05.

Fig 4: Transcriptional levels of TRAIL, OPG, and BAFF in COVID‐19 patients. OPG, BAFF and TRAIL (A–C, respectively) levels were evaluated using qPCR in healthy donors (HD) and COVID‐19 patients. OPG levels significantly differ between HD and COVID‐19, mildly affected and moderately affected, and mildly affected and severely affected patients. BAFF levels significantly differ between HD and COVID‐19, mildly affected and moderately affected, and mildly affected and severely affected patients. TRAIL levels significantly differ between HD and COVID‐19 and mild and severely affected patients. Data are presented as mean +/− SD (red); each symbol represents an individual subject, and HD levels were normalized to 1 as a reference. Statistical analysis was performed with the Mann–Whitney U test to compare two groups (A–C, left) or the Kruskal–Wallis test and corrected using Dunn's test to compare between groups (A–C, right). ****p < 0.0001, ***p < 0.001, **p < 0.01 and *p < 0.05.

Fig 5: OPG and TNFR1 levels are increased in Frail patients post-COVID-19. A plasma sample was obtained from post-COVID-19 patients at 4 months and divided into non-frail (n=8) and frail (n=18), and a second sample was obtained at 12 months and divided into non-frail (n=8) and frail (n=10). OPG, TNFR1, and BAFF were evaluated using ELISA. The green dotted line represents the mean value of the control groups (taken from previous graphics). Data are presented as mean ± standard deviation; each symbol represents an individual subject. p-values were calculated by Kruskal–Wallis, followed by Dunn’s post-hoc test. *p<0.05.