Dataset Information

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19.

ABSTRACT: Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.

SUBMITTER: Martinez-Fleta P

PROVIDER: S-EPMC8787267 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19.

Martínez-Fleta Pedro P Vera-Tomé Paula P Jiménez-Fernández María M Requena Silvia S Roy-Vallejo Emilia E Sanz-García Ancor A Lozano-Prieto Marta M López-Sanz Celia C Vara Alicia A Lancho-Sánchez Ángel Á Martín-Gayo Enrique E Muñoz-Calleja Cecilia C Alfranca Arantzazu A González-Álvaro Isidoro I Galván-Román José María JM Aspa Javier J de la Fuente Hortensia H Sánchez-Madrid Francisco F

Frontiers in immunology 20220111

Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a s ...[more]

PMID: 35087533

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Project description:Abstract Background Coronavirus disease 2019 (COVID-19) results from SARS-CoV-2-induced hyperinflammatory immune response, orchestrated by granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF increases interleukin-6 (IL-6) levels, ultimately leading to increased C-reactive protein (CRP). The LIVE-AIR trial demonstrated that lenzilumab, the GM-CSF neutralizing antibody, improved the likelihood of survival without invasive mechanical ventilation (IMV) in hospitalized COVID-19 patients requiring supplemental oxygen but not IMV. This sub-analysis correlated levels of cytokines before and after lenzilumab treatment. Methods LIVE-AIR was a phase 3, randomized, double-blind, placebo-controlled trial (NCT04351152). Patients hospitalized with COVID-19 pneumonia, requiring only supplemental oxygen, were randomized to receive lenzilumab (1800 mg in three equally divided doses of 600 mg, q8h) or placebo IV infusion, in addition to standard of care which included remdesivir and corticosteroids. Blood taken at baseline (BL) and subsequent to treatment through day 10 (D10) were obtained and analyzed by high sensitivity enzyme immunoassay for GM-CSF, IL-6, and CRP. Results Baseline IL-6 levels (Loge-transformed for all cytokines and biomarkers) were linearly correlated with higher baseline GM-CSF levels (slope=0.60, p< 0.001). Baseline CRP levels were linearly correlated with higher baseline IL-6 levels (slope=0.29, p < 0.001). GM-CSF levels decreased with lenzilumab treatment on day 1 (D1) which persisted through D10 (Table). In contrast, GM-CSF increased with placebo treatment. IL-6 levels decreased only with lenzilumab treatment. CRP following lenzilumab or placebo treatment decreased on D1 to similar levels and further decreased on D10 only with lenzilumab treatment. Cytokine Levels Associated with Lenzilumab Treatment Conclusion Lenzilumab decreased GM-CSF as well as downstream cytokines and systemic biomarkers of inflammation during the hyperinflammatory immune response of COVD-19. Disclosures Dale Chappell, MD, MBA, Humanigen, Inc: Employee|Humanigen, Inc: Ownership Interest Adrian Kilcoyne, MD, Humanigen, Inc: Employee Frank Cerasoli, PhD, Humanigen, Inc: Advisor/Consultant John Lukas, PhD, Humanigen, Inc: Advisor/Consultant Cameron Durrant, MD, Humanigen, Inc: Employee|Humanigen, Inc: Ownership Interest Zelalem Temesgen, MD, Gilead: unrestricted educational grant (to the institution)|Humanigen, Inc: Grant/Research Support|Merck: unrestricted educational grant (to the institution)|ViiV: Advisor/Consultant Christopher Polk, MD, Gilead: Advisor/Consultant Jason Baker, MD, Gilead: Grant/Research Support|Humanigen, Inc: Grant/Research Support Vincent Marconi, MD, Gilead: Grant/Research Support.

Project description:This prospective observational study compared the 1H NMR blood lipidomes and metabolomes of 71 patients with community-acquired pneumonia (CAP), 75 patients with COVID-19 pneumonia, and 75 healthy controls (matched by age and sex) to identify potential biomarkers and pathways associated with respiratory infections. Both pneumonia groups had comparable severity indices, including mortality, invasive mechanical ventilation, and intensive care unit admission rates. Patients with COVID-19 pneumonia exhibited more pronounced hypolipidemia, with significantly lower levels of total cholesterol and LDL-c compared to patients with CAP. Atherogenic lipoprotein subclasses (VLDL-cholesterol, IDL-cholesterol, IDL-triglyceride, and LDL-triglyceride/LDL-cholesterol) were significantly increased in severe cases of both pneumonia types, while lower HDL-c and small, dense HDL particles were associated with more severe illness. Both infected groups showed decreased esterified cholesterol and increased triglycerides, along with reduced phosphatidylcholine, lysophosphatidylcholine, PUFA, omega-3 fatty acids, and DHA. Additionally, infected patients had elevated levels of glucose, lactate, 3-hydroxybutyrate, and acetone, which are linked to inflammation, hypoxemia, and sepsis. Increased levels of branched-chain amino acids, alanine, glycine, and creatine, which are involved in energy metabolism and protein catabolism, were also observed. Neurotransmitter synthesis metabolites like histidine and glutamate were higher in infected patients, especially those with COVID-19. Notably, severe infections showed a significant decrease in glutamine, essential for lymphocyte and macrophage energy. The severity of COVID-19 pneumonia was also associated with elevated glycoprotein levels (glycoprotein A, glycoprotein B, and glycoprotein F), indicating an inflammatory state. These findings suggest that metabolomic and lipidomic changes in pneumonia are connected to bioenergetic pathways regulating the immune response.

Project description:Background: Corona virus disease (COVID-19) is an infectious respiratory disease that has spread rapidly across the world. Many studies have already evaluated the clinical features of COVID-19, but how it compares with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) is still unclear. Moreover, COVID-19 mortality is correlated with disease severity, but indicators for severity grading have not been specified. We aimed to analyze the clinical characteristics of COVID-19 in comparison with SN-CAP and find indicators for disease severity in COVID-19. Methods: Patients diagnosed with COVID-19 and SN-CAP were enrolled. Clinical, radiological, and laboratory data were analyzed. Results: The numbers of COVID-19 and SN-CAP patients enrolled were 304 and 138, respectively. The age of the patients was not significantly different between the groups. Compared with SN-CAP, COVID-19 patients had more symptoms of fever and dyspnea; and showed significant difference in blood count results. Computed tomography (CT) imaging of COVID-19 patients showed patchy ground-glass opacities that correlated with disease severity, whereas the CT imaging of SN-CAP patients showed patchy high-density shadows. COVID-19 patients were classified into moderate, severe, and critically severe groups. The severe and critically severe groups had elevated levels of white blood cells (WBC), neutrophils, platelets, C-reaction protein (CRP), lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), troponin-I, creatinine, and blood urea nitrogen (BUN). However, they had decreased levels of lymphocytes, lymphocyte ratio, and albumin. Compared with the younger patients, the older COVID-19 individuals had more chronic diseases and significantly elevated levels of WBC, neutrophil, and CRP levels. Conclusion: SN-CAP showed more inflammatory reaction than COVID-19. Old people with chronic diseases are more susceptible to COVID-19 and have a high likelihood of developing severe and critically severe infection. Levels of WBC, lymphocytes, neutrophils, CRP, NLR, PLR, troponin-I, creatinine, and BUN are important indicators for severity grading in COVID-19.

Dataset Information

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19.

Publications

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19.

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