Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Elevated Levels of Soluble CD147 are Associated with Hyperinflammation and Disease Severity in COVID-19: A Proof-of-Concept Clinical Study.

To evaluate soluble CD147 levels in COVID-19 and identify whether these are associated with hyperinflammation and disease severity. One-hundred and nine COVID-19 patients and 72 healthy blood donors were studied. Levels of CD147, matrix metalloproteases (MMP) and inflammatory markers were measured on hospital arrival, while the need for mechanical ventilation and the occurrence of death during hospitalization were recorded. CD147 levels were higher in COVID-19 (1.6, 1.0-2.3 vs 1.3, 1.0-1.6 ng/ml; P = 0.003) than controls. MMP-2 (9.2, 4.5-12.9 vs 4.2, 3.7-4.6 ng/ml; P < 0.001), MMP-3 (1.1, 0.9-1.3 vs 0.9, 0.7-1.0 ng/ml; P < 0.001) and MMP-9 (0.9, 0.5-1.2 vs 0.4, 0.2-0.6 ng/ml; P < 0.001) were also higher in COVID-19, while MMP-1 (0.6, 0-1.4 vs 0.6, 0.3-0.7 ng/ml; P = 0.711) was not different. Significant correlations were found between CD147 and MMP-2 (ρ = 0.34), MMP-3 (ρ = 0.21), interleukin 6 (ρ = 0.21), and the neutrophil/lymphocyte ratio (ρ = 0.26). Furthermore, CD147 levels were higher in patients who required mechanical ventilation (1.8, 1.4-2.4 vs 1.2, 0.8-1.9 ng/ml; P < 0.001) and in those who ultimately died (1.9, 1.4-2.7 vs 1.4, 0.9-1.9 ng/ml; P = 0.009). CD147 is elevated in COVID-19 and appears to contribute to hyperinflammation and disease severity.

The prognostic importance of the angiotensin II/angiotensin-(1-7) ratio in patients with SARS-CoV-2 infection.

BACKGROUND: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1-7) levels in patients with COVID-19 is scarce. OBJECTIVE: To characterize the Ang II-ACE2-Ang-(1-7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. METHODS: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1-7), and Ang-(1-9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). RESULTS: Serum from 74 patients [age: 58 (48-67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10-21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1-7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1-7) concentration was lower in patients who died. The Ang II/Ang-(1-7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1-7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 103/µl (OR = 8.43) were independent predictors of mortality from COVID-19. CONCLUSION: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II-ACE2-Ang-(1-7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients.

BACKGROUND: Several easy-to-use risk scoring systems have been built to identify patients at risk of developing complications associated with COVID-19. However, information about the ability of each score to early predict major adverse outcomes during hospitalization of severe COVID-19 patients is still scarce. METHODS: Eight risk scoring systems were rated upon arrival at the Emergency Department, and the occurrence of thrombosis, need for mechanical ventilation, death, and a composite that included all major adverse outcomes were assessed during the hospital stay. The clinical performance of each risk scoring system was evaluated to predict each major outcome. Finally, the diagnostic characteristics of the risk scoring system that showed the best performance for each major outcome were obtained. RESULTS: One hundred and fifty-seven adult patients (55 ± 12 years, 66% men) were assessed at admission to the Emergency Department and included in the study. A total of 96 patients (61%) had at least one major outcome during hospitalization; 32 had thrombosis (20%), 80 required mechanical ventilation (50%), and 52 eventually died (33%). Of all the scores, Obesity and Diabetes (based on a history of comorbid conditions) showed the best performance for predicting mechanical ventilation (area under the ROC curve (AUC), 0.96; positive likelihood ratio (LR+), 23.7), death (AUC, 0.86; LR+, 4.6), and the composite outcome (AUC, 0.89; LR+, 15.6). Meanwhile, the inflammation-based risk scoring system (including leukocyte count, albumin, and C-reactive protein levels) was the best at predicting thrombosis (AUC, 0.63; LR+, 2.0). CONCLUSIONS: Both the Obesity and Diabetes score and the inflammation-based risk scoring system appeared to be efficient enough to be integrated into the evaluation of COVID-19 patients upon arrival at the Emergency Department.