Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 17, 2022

A disease outbreak in December 2019, caused by a novel coronavirus SARS-CoV-2, was named COVID-19. SARS-CoV-2 infects cells from the upper and lower respiratory tract system is transmitted inhalation or contact with infected droplets. Common clinical symptoms include fatigue, fever, cough, but also shortness of breath lung abnormalities. Still, some 5% infections progress to severe pneumonia acute distress syndrome (ARDS), pulmonary edema, kidney injury, and/or multiple organ failure as important consequences, which can lead death. The innate immune recognizes viral RNAs triggers expression interferons (IFN). IFNs activate anti-viral effectors components adaptive activating members STAT IRF families that induce IFN-stimulated genes (ISG)s. Among other coronaviruses, such Middle East (MERS-CoV) SARS-CoV, common strategies have been identified antagonize IFN signaling. This typically coincides hyperactive inflammatory host responses known “cytokine storm” mediate damage. Likewise, infection combines dysregulated response excessive production cytokines lungs. lungs associated local recruitment create pathogenic loop. Together, it causes pathology, including ARDS, well damage vulnerable organs, like heart, spleen, lymph nodes, kidney, brain. rapidly exhaustion correlates poor prognosis COVID-19 patients. In this review, we focus on crucial role different types underlies progression leads cell hyper-activation lungs, exuberant systemic inflammation, Consequently, protect will be critical interfere signaling cascades activated cytokines. Targeting family could therefore proposed therapeutic strategy patients

Language: Английский

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Complement activation in COVID-19 and targeted therapeutic options: A scoping review

Blood Reviews, Journal Year: 2022, Volume and Issue: 57, P. 100995 - 100995

Published: July 31, 2022

Increasing evidence suggests that activation of the complement system plays a key role in pathogenesis and disease severity Coronavirus 2019 (COVID-19). We used systematic approach to create an overview COVID-19 based on histopathological, preclinical, multiomics, observational clinical interventional studies. A total 1801 articles from PubMed, EMBASE Cochrane was screened which 157 were included this scoping review. Histopathological, multiomics studies showed apparent through all three pathways correlation with mortality. The targeted at different levels COVID-19, C5 C5a inhibition seem most promising. Adequately powered, double blind RCTs are necessary order further investigate effect targeting COVID-19.

Language: Английский

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COVID-19 and Acute Kidney Injury

Critical Care Clinics, Journal Year: 2022, Volume and Issue: 38(3), P. 473 - 489

Published: Jan. 10, 2022

Language: Английский

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Renin‐Angiotensin System Inhibitors in Patients With COVID‐19: A Meta‐Analysis of Randomized Controlled Trials Led by the International Society of Hypertension

Journal of the American Heart Association, Journal Year: 2022, Volume and Issue: 11(17)

Published: Aug. 24, 2022

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis RASi Methods Results MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Controlled Trial Register were searched that randomly assigned patients COVID-19 continuation/commencement versus no therapy. The primary outcome was all-cause mortality at ≤30 days. A total 14 met inclusion criteria enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of trials, 11 contributed data. found effect control on (7.2% 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or subgroups defined by severity trial type. Network identified difference between angiotensin-converting enzyme angiotensin II receptor blockers. users had nonsignificant reduction acute myocardial infarction (2.1% 3.6%; RR, 0.59; 0.33-1.06]), but increased kidney injury (7.0% 1.82; 1.05-3.16]), initiated continued RASi. There increase need dialysis differences congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, mechanical ventilation. Conclusions This evaluating inhibitors/angiotensin blockers mortality, borderline decrease infarction, an Our findings provide strong evidence can be used safely

Language: Английский

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Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: July 25, 2022

Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence AKI and use replacement therapy (KRT) in COVID-19, assess patient outcomes risk factors for differences outcome when diagnosis is based on urine output (UO) or serum creatinine (sCr).

Language: Английский

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