Graphical Abstract Highlights d Severe COVID-19 patients display immune dysregulation or macrophage activation syndrome d Severe respiratory failure is associated with a major decrease of HLA-DR on CD14 monocytes d CD4 cell and NK cell cytopenias are characteristics of severe COVID-19 d IL-6 blocker Tocilizumab partially rescues SARS-CoV-2associated immune dysregulation

Background:The pneumonia of COVID-19 illness has often a subtle initial presentation making mandatory the use of biomarkers for evaluation of severity and prediction of final patient disposition. We evaluated the use of hydrogen sulfide (H2S) for the outcome of COVID-19 pneumonia. Materials & Methods:We studied 74 patients with COVID-19. Clinical data were collected, and survival predictors were calculated. Blood was collected within 24 hours after admission (day 1) and on day 7. H2S was measured in sera by monobromobimanederivation (MBB) followed by high performance liquid chromatography and correlated to other markers likeprocalcitonin (PCT) and C-reactive protein (CRP). Tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 were also measured in serum. Results:Survivors had significantly higher H2S levels on day 1 and 7 after admission. A cutoff point of 150.44 μM could discriminate survivors from non-survivors with 80% sensitivity, 73.4% specificity and negative predictive value 95.9%. Mortality after 28 days was 32% with admission levels lower or equal to 150.44μΜ and 4.1% with levels above 150.44μΜ (p: 0.0008). Mortality was significantly greater among patients with a decrease of H2S levels from day 1 to day 7 greater or equal to 36% (p: 0.0005). Serum H2S on day 1 was negatively correlated with IL-6 and CRP and positively correlated with the absolute lymphocyte countin peripheral blood. Conclusion: It is concluded that H2S is a potential marker for severity and final outcome of pneumonia by the SARS-CoV-2 coronavirus. Its correlation with IL-6 suggests antiinflammatory properties.