C3a and C5b-9 Differentially Predict COVID-19 Progression and Outcome.

SARS-CoV-2 infection may result in severe pneumonia leading to mechanical ventilation and intensive care (ICU) treatment. Complement activation was verified in COVID-19 and implicated as a contributor to COVID-19 pathogenesis. This study assessed the predictive potential of complement factors C3a and C5b-9 for COVID-19 progression and outcome. We grouped 80 COVID-19 patients into severe COVID-19 patients (n = 38) and critically ill (n = 42) and subdivided into non-intubated (n = 48) and intubated (n = 32), survivors (n = 57) and non-survivors (n = 23). Results: A significant increase for C3a and C5b-9 levels was observed between: severely and critically ill patients (p < 0.001 and p < 0.0001), non-intubated vs intubated (p < 0.001 and p < 0.05), survivors vs non-survivors (p < 0.001 and p < 0.01). ROC analysis for the need for ICU treatment revealed a higher AUC for C5b-9 (0.764, p < 0.001) compared to C3a (AUC = 0.739, p < 0.01). A higher AUC was observed for C3a for the need for intubation (AUC = 0.722, p < 0.001) or mortality (AUC = 0.740, p < 0.0001) compared to C5b-9 (need for intubation AUC = 0.656, p < 0.05 and mortality AUC = 0.631, p = NS). Combining the two markers revealed a powerful prediction tool for ICU admission (AUC = 0.773, p < 0.0001), intubation (AUC = 0.756, p < 0.0001) and mortality (AUC = 0.753, p < 0.001). C3a and C5b-9 may be considered as prognostic tools separately or in combination for the progression and outcome of COVID-19.

Increase of HO-1 Expression in Critically Ill COVID-19 Patients Is Associated with Poor Prognosis and Outcome.

Heme-oxygenase (HO)-1 is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties and previous reports have also emphasized the antiviral properties of HO-1, either directly or via induction of interferons. To investigate the potential role of HO-1 in patients with coronavirus disease 2019 (COVID-19), the present study assessed changes in HO-1 expression in whole blood and tissue samples. Upregulation of HO-1 protein was observed in lung, liver, and skin tissue independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence. A significant increase of blood HO-1 mRNA levels was observed in critically ill COVID-19 patients compared to those in severe COVID-19 patients and healthy controls. This increase was accompanied by significantly elevated levels of serum ferritin and bilirubin in critically ill compared to patients with severe disease. Further grouping of patients in survivors and non-survivors revealed a significant increase of blood HO-1 mRNA levels in the later. Receiver operating characteristic (ROC) analysis for prediction of ICU admission and mortality yielded an AUC of 0.705 (p = 0.016) and 0.789 (p = 0.007) respectively indicating that HO-1 increase is associated with poor COVID-19 progression and outcome. The increase in HO-1 expression observed in critically ill COVID-19 patients could serve as a mechanism to counteract increased heme levels driving coagulation and thrombosis or as an induced protective mechanism.

Thyroid hormone alterations in critically and non-critically ill patients with SARS-CoV-2 infection.

OBJECTIVE: Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients. DESIGN: Cohort observational study. METHODS: We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism. RESULTS: A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of negative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare. CONCLUSIONS: NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients.