ABSTRACT
COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.
Subject(s)
Biomarkers/blood , Carbon/metabolism , Liver/metabolism , Metabolome , Nitrogen/metabolism , Amino Acids/metabolism , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cytokines/blood , Discriminant Analysis , Humans , Least-Squares Analysis , Metabolic Networks and Pathways/genetics , Metabolomics/methods , SARS-CoV-2/isolation & purification , Severity of Illness IndexABSTRACT
Coronavirus disease 2019 (COVID-19) may have a wide spectrum of clinical presentations, leading in some cases to a critical condition with poor long-term outcomes and residual disability requiring post-acute rehabilitation. A major concern in severe COVID-19 is represented by a concomitant prothrombotic state. However, contrasting data are available about the prevalence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE). A detailed search on the association of COVID-19 with thromboembolic complications was conducted in the main electronic databases (PubMed, Web of Science, and Scopus) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The weighted mean prevalence (WMP) with 95% confidence interval (95% CI) was calculated with the random-effects model. Twenty studies enrolling 1,988 COVID-19 patients were included. The WMP of VTE was 31.3% (95% CI: 24.3-39.2%). The WMP of DVT was 19.8% (95% CI: 10.5-34.0%), whereas the WMP of PE was 18.9% (95% CI: 14.4-24.3%). Similar results were obtained when specifically analyzing studies on patients admitted to intensive care units and those on patients under antithrombotic prophylaxis. Regression models showed that an increasing age was associated with a higher prevalence of VTE (Z-score: 3.11, p = 0.001), DVT (Z-score: 2.33, p = 0.002), and PE (Z-score: 3.03, p = 0.002), while an increasing body mass index was associated with an increasing prevalence of PE (Z-score = 2.01, p = 0.04). Male sex did not impact the evaluated outcomes. The rate of thromboembolic complications in COVID-19 patients is definitely high. Considering the risk of fatal and disabling complications, adequate screening procedures and antithrombotic strategies should be implemented.
Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Pulmonary Embolism/complications , Venous Thromboembolism/complications , Venous Thrombosis/complications , Anticoagulants/adverse effects , Betacoronavirus , Body Mass Index , COVID-19 , Critical Care/methods , Female , Fibrinolytic Agents/adverse effects , Humans , Intensive Care Units , Male , Pandemics , Prevalence , Prognosis , Pulmonary Embolism/drug therapy , Regression Analysis , Risk , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Venous Thrombosis/drug therapyABSTRACT
Background: Complications of coronavirus disease 2019 (COVID-19) include coagulopathy. We performed a meta-analysis on the association of COVID-19 severity with changes in hemostatic parameters. Methods: Data on prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer, platelets (PLT), or fibrinogen in severe versus mild COVID-19 patients, and/or in non-survivors to COVID-19 versus survivors were systematically searched. The standardized mean difference (SMD) was calculated. Results: Sixty studies comparing 5487 subjects with severe and 9670 subjects with mild COVID-19 documented higher PT (SMD: 0.41;95%CI: 0.21, 0.60), D-Dimer (SMD: 0.67;95%CI: 0.52, 0.82), and fibrinogen values (SMD: 1.84;95%CI: 1.21, 2.47), with lower PLT count (SMD: −0.74;95%CI: −1.01, −0.47) among severe patients. Twenty-five studies on 1511 COVID-19 non-survivors and 6287 survivors showed higher PT (SMD: 0.67;95%CI: 0.39, 0.96) and D-Dimer values (SMD: 3.88;95%CI: 2.70, 5.07), with lower PLT count (SMD: −0.60, 95%CI: −0.82, −0.38) among non-survivors. Regression models showed that C-reactive protein values were directly correlated with the difference in PT and fibrinogen. Conclusions: Significant hemostatic changes are associated with COVID-19 severity. Considering the risk of fatal complications with residual chronic disability and poor long-term outcomes, further studies should investigate the prognostic role of hemostatic parameters in COVID-19 patients.