IL-6, IL-10, sFas, granulysin and indicators of intestinal permeability as early biomarkers for a fatal outcome in COVID-19.

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges between mild respiratory symptoms and a severe disease that shares many of the features of sepsis. Sepsis is a deregulated response to infection that causes life-threatening organ failure. During sepsis, the intestinal epithelial cells are affected, causing an increase in intestinal permeability and allowing microbial translocation from the intestine to the circulation, which exacerbates the inflammatory response. Here we studied patients with moderate, severe and critical COVID-19 by measuring a panel of molecules representative of the innate and adaptive immune responses to SARS-CoV-2, which also reflect the presence of systemic inflammation and the state of the intestinal barrier. We found that non-surviving COVID-19 patients had higher levels of low-affinity anti-RBD IgA antibodies than surviving patients, which may be a response to increased microbial translocation. We identified sFas and granulysin, in addition to IL-6 and IL-10, as possible early biomarkers with high sensitivity (>73 %) and specificity (>51 %) to discriminate between surviving and non-surviving COVID-19 patients. Finally, we found that the microbial metabolite d-lactate and the tight junction regulator zonulin were increased in the serum of patients with severe COVID-19 and in COVID-19 patients with secondary infections, suggesting that increased intestinal permeability may be a source of secondary infections in these patients. COVID-19 patients with secondary infections had higher disease severity and mortality than patients without these infections, indicating that intestinal permeability markers could provide complementary information to the serum cytokines for the early identification of COVID-19 patients with a high risk of a fatal outcome.

IL-6, IL-10, sFas, granulysin and indicators of intestinal permeability as early biomarkers for a fatal outcome in COVID-19

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges between mild respiratory symptoms and a severe disease that shares many of the features of sepsis. Sepsis is a deregulated response to infection that causes life-threatening organ failure. During sepsis, the intestinal epithelial cells are affected, causing an increase in intestinal permeability and allowing microbial translocation from the intestine to the circulation, which exacerbates the inflammatory response. Here we studied patients with moderate, severe and critical COVID-19 by measuring a panel of molecules representative of the innate and adaptive immune responses to SARS-CoV-2, which also reflect the presence of systemic inflammation and the state of the intestinal barrier. We found that non-surviving COVID-19 patients had higher levels of low-affinity anti-RBD IgA antibodies than surviving patients, which may be a response to increased microbial translocation. We identified sFas and granulysin, in addition to IL-6 and IL-10, as possible early biomarkers with high sensitivity (>73%) and specificity (>51%) to discriminate between surviving and non-surviving COVID-19 patients. Finally, we found that the microbial metabolite D-lactate and the tight junction regulator zonulin were increased in the serum of patients with severe COVID-19 and in COVID-19 patients with secondary infections, suggesting that increased intestinal permeability may be a source of secondary infections in these patients. COVID-19 patients with secondary infections had higher disease severity and mortality than patients without these infections, indicating that intestinal permeability markers could provide complementary information to the serum cytokines for the early identification of COVID-19 patients with a high risk of a fatal outcome.

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease.

AIM: Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. METHODS: Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n = 166) and validated (n = 170). RESULTS: Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P < 0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4 ± 341.2 vs. 41.3 ± 41.1, aspartate aminotransferase (AST) 325.3 ± 382.4 vs. 52.8 ± 47.1, lactic dehydrogenase (LDH) 764.6 ± 401.9 vs. 461.0 ± 185.6, D-dimer (DD) 7765 ± 9109 vs. 1871 ± 4146, and age 58.6 ± 12.7 vs. 49.1 ± 12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity = 0.797 and specificity = 0.391, c - statistic = 0.74; 95%IC: 0.62-0.86, P < 0.001), to predict the risk of need admission to ICU (OR = 5.8; 95% CI: 2.2-15.4, P = 0.001), was constructed. Validation cohort: in 170 different patients, the AAD model < 2.75 (c - statistic = 0.80 (95% CI: 0.70-0.91, P < 0.001) adequately predicted the risk (OR = 8.8, 95% CI: 3.4-22.6, P < 0.001) to be admitted in the ICU (27 patients, 15.95%). CONCLUSIONS: The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19.

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current pandemic, can have multi-organ impact. Recent studies show that liver injury could be a manifestation of the disease, and that liver disease could also be related to a worse prognosis. Our aim was to compare the characteristics of patients with severe coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation, specifically in Mexican. METHODS: This was an observational case-control study nested in a cohort study. Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed. Clinical and biochemical data were collected, and the characteristics of patients who required invasive mechanical ventilation (IMV) (cases) were compared with stable hospitalized patients without ventilation (controls). RESULTS: We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection; 114 (68.7%) were men, the mean age was 50.6 ± 13.3 years, and 27 (16.3%) required IMV. The comparative analysis between cases and controls showed (respectively) significantly lower blood oxygen saturation (SpO2) (73.5 ± 12.0% vs. 83.0 ± 6.8%, P < 0.0001) and elevated alanine aminotransferase (ALT) (128 (14-1123) IU/L vs. 33 (8-453) IU/L, P = 0.003), aspartate aminotransferase (AST) (214 (17-1247) vs. 44 (12-498) IU/L, P = 0.001), lactic dehydrogenase (LDH) (764.6 ± 401.9 IU/L vs. 461.0 ± 185.6 IU/L, P = 0.001), and D-dimer (3463 (524-34,227) ng/mL vs. 829 (152-41,923) ng/mL, P = 0.003) concentrations. Patients in the cases group were older (58.6 ± 12.7 years vs. 49.1 ± 12.8 years, P=0.001). Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST ≥250 IU/L (odds ratio (OR) = 64.8, 95% confidence interval (CI) 7.5-560.3, P < 0.0001) and D-dimer ≥ 3500 ng/mL (OR = 4.1, 95% CI 1.2-13.7, P=0.02). CONCLUSIONS: Our study confirms the importance of monitoring liver enzymes in hospitalized patients with COVID-19; seriously ill patients have significantly elevated AST and D-dimer concentrations, which have prognostic implications in the SARS-CoV-2 disease course.