Proinflammatory and Hepatic Features Related to Morbidity and Fatal Outcomes in COVID-19 Patients

Abstract

Objective: to screen putative associations between liver markers and proinflammatory-related features concerning infectious morbidity and fatal outcomes in COVID-19 patients. Methods: a total of 2094 COVID-19 positive patients from the COVID-DATA-SAFE-LIFES cohort (HM hospitals consortium) were classified according to median values of hepatic, inflammatory, and clinical indicators. Logistic regression models were fitted and ROC cures were generated to explain disease severity and mortality. Results: intensive care unit (ICU) assistance plus death outcomes were associated with liver dysfunction, hyperinflammation, respiratory insufficiency, and higher associated comorbidities. Four models including age, sex, neutrophils, D-dimer, oxygen saturation lower than 92%, C-reactive protein (CRP), Charlson Comorbidity Index (CCI), FIB-4 and interactions with CRP, neutrophils, and CCI explained ICU plus death variance in more than 28%. The predictive values of ROC curves were: FIB-4 (0.7339), AST/ALT ratio (0.7107), CRP (0.7003), CCI index (0.6778), neutrophils (0.6772), and platelets (0.5618) concerning ICU plus death outcomes. Conclusions: the results of this research revealed that liver and proinflammatory features are important determinants of COVID-19 morbidity and fatal outcomes, which could improve the current understanding of the COVID-19 physiopathology as well as to facilitate the clinical management and therapy decision-making of this disease under a personalized medicine scope.

Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department

“…This association persisted in the multivariable survival model after adjustment for potential confounders and for the severity of respiratory failure. In particular, when we built the ROC curves for mortality, we found an AUC of 0.73 for the FIB-4 score that is in line with recent studies [ 23 , 24 ].…”

Physiological Network Is Disrupted in Severe COVID-19

“…In agreement with current knowledge ( Supplementary Table 4 ), well-known cardiovascular biomarkers such as ultrasensitive troponin ( Zhu et al, 2021 ), C-reactive protein, and lactic dehydrogenase were increased in the groups with fatal outcome ( Supplementary Table 4 ). Our work reinforces the role of other less well identified biomarkers such as hepatic features ( Ramos-Lopez et al, 2021 ) and pulmonary artery diameters ( Spagnolo et al, 2020 ). We also provide evidence that several biomarkers could benefit from adjusted thresholds by sex such as ferritin, respectively ( Supplementary Table 4 ).…”

Longwise Cluster Analysis for the Prediction of COVID-19 Severity within 72 h of Admission: COVID-DATA-SAVE-LIFES Cohort

“…A specific implication of severe COVID-19 in NAFLD patients putatively mediated by immunocompetence status is highlighted in the B cluster, where transaminases and liver health markers showed abnormal values and may drive personalized medicine approaches, as prompted by the allocation to a cluster with related measurements uncovering therapeutic targets. In a previous report, patients concerning this COVID-DATA-SAFE-LIFES cohort were categorized following conventional criteria to explain disease severity and deaths, which verified that liver and proinflammatory features are important determinants of COVID-19 morbidity and mortality in order to ameliorate the understanding of morbid manifestations of COVID-19, besides to help the therapy decision-making protocols under a personalized medicine scope [ 11 ]. Indeed, the liver health and coagulation axis appears as a relevant surrogate for elucidating some COVID-19 outcomes linked to systemic inflammation [ 43 ], as well as thrombotic and fibrinolytic disturbances [ 44 ], which were deciphered in the currently emerged three clusters, including some markers of global health such as lactate dehydrogenase or creatinine/urea measurements [ 45 ], as particularly discriminated in Cluster C. Interestingly, hemoglobin and prothrombin values evidenced divergent patterns after the following 72-h period, which represent a worth for a cluster monitor.…”

“…The delay of detection and hospitalization has a large impact on the concurrent inflammatory stage, and, thus, on the prognosis and the fatality of the disease [ 7 ]. These manifestations are accompanied by microvascular damages caused by the cytokine “storm” [ 8 ], and often, the pathophysiological COVID-19 condition is also associated with bacterial infections [ 9 ] and with body metabolic impairments [ 10 , 11 ], where prescribed anti-inflammatory medications also may play a role [ 12 ].…”