Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(5), P. 319 - 329

Published: April 6, 2021

Language: Английский

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The immunology and immunopathology of COVID-19

Science, Journal Year: 2022, Volume and Issue: 375(6585), P. 1122 - 1127

Published: March 10, 2022

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify drivers of and fatal COVID-19, understand what leads prolongation symptoms after disease resolution. We review results almost years COVID-19 immunology discuss definitive findings remaining questions regarding our understanding pathophysiology. emerging differences in responses seen those with without Long Covid syndrome, also known as post-acute sequelae SARS-CoV-2. hope that knowledge gained from this will be applied studies inflammatory processes involved critical chronic illnesses, which remain a major unmet need.

Language: Английский

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COVID-19: A Global Challenge with Old History, Epidemiology and Progress So Far

Molecules, Journal Year: 2020, Volume and Issue: 26(1), P. 39 - 39

Published: Dec. 23, 2020

Humans have witnessed three deadly pandemics so far in the twenty-first century which are associated with novel coronaviruses: SARS, Middle East respiratory syndrome (MERS), and COVID-19. All of these viruses, responsible for causing acute tract infections (ARTIs), highly contagious nature and/or caused high mortalities. The recently emerged COVID-19 disease is a transmittable viral infection by another zoonotic coronavirus named severe 2 (SARS-CoV-2). Similar to other two coronaviruses such as SARS-CoV-1 MERS-CoV, SARS-CoV-2 also likely originated from bats, been serving established reservoirs various pathogenic coronaviruses. Although, it still unknown how transmitted bats humans, rapid human-to-human transmission has confirmed widely. first appeared Wuhan, China, December 2019 quickly spread across globe, infected 48,539,872 people, 1,232,791 deaths 215 countries, spreading at time manuscript preparation. So far, there no definite line treatment approved or vaccine available. However, different types potential vaccines therapeutics evaluated under clinical trials against In this review, we summarize diseases briefly discuss earlier outbreaks compare their occurrence pathogenicity current pandemic. Various epidemiological aspects mode spread, death rate, doubling time, etc., discussed detail. Apart this, technical issues related pandemic including use masks socio-economic problems summarized. Additionally, reviewed patient management strategies mechanism action, available diagnostic tools, development effective therapeutic combinations deal outbreak. Overall, inclusion references, review covers, detail, most important

Language: Английский

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Pathophysiology of COVID-19-associated acute kidney injury

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(11), P. 751 - 764

Published: July 5, 2021

Language: Английский

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Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin

Cardiovascular Diabetology, Journal Year: 2021, Volume and Issue: 20(1)

Published: Aug. 23, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of disease 2019 (COVID-19), is characterized by clinical pathologies, including various coagulopathies that may be accompanied hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from symptoms. This commonly termed Long COVID/Post-Acute Sequelae (PASC). Here we refer to it as COVID/PASC. Lingering symptoms persist for much 6 months (or longer) where survivors complain recurring fatigue or muscle weakness, being out breath, sleep difficulties, anxiety depression. Given blood clots can block microcapillaries thereby inhibit oxygen exchange, here investigate if lingering individuals with COVID/PASC manifest might due presence persistent circulating plasma microclots are resistant fibrinolysis.We use techniques proteomics fluorescence microscopy study samples healthy individuals, Type Diabetes Mellitus (T2DM), COVID-19, those symptoms.We show still contain large anomalous (amyloid) deposits (microclots). We also these both fibrinolysis (compared controls T2DM), even trypsinisation. After second trypsinization, pellet (microclots) were solubilized. detected inflammatory molecules substantially increased supernatant trapped solubilized COVID/PASC, versus equivalent volume fully digested fluid control T2DM. Of particular interest was substantial increase α(2)-antiplasmin (α2AP), fibrinogen chains, well Serum Amyloid A (SAA) fibrinolytic-resistant deposits.Clotting pathologies infection benefit following regime continued anticlotting therapy support fibrinolytic system function.

Language: Английский

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The state of complement in COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(2), P. 77 - 84

Published: Dec. 15, 2021

Language: Английский

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SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

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Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: March 22, 2022

Abstract Background Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis damaging endothelium, we investigated dysfunction (ED) biomarkers in PCS. Methods We studied function 30 PCS persistent fatigue as well 15 age- sex matched seronegative healthy controls (HCs). 14 fulfilled diagnostic ME/CFS. The other were considered to have Peripheral was assessed by reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) HCs. In larger cohort HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) ACE2 analysed biomarkers. Results Five ME/CFS five 16 showed ED defined diminished RHI (< 1.67), but none HCs exhibited this finding. A paradoxical positive correlation age, blood pressure BMI found not patients. ET-1 concentration significantly elevated both compared PCHCs. serum Ang-2 lower PCHCs Conclusion display evidence shown altered Different associations clinical parameters varying biomarker profiles may suggest distinct pathomechanisms patient subgroups.

Language: Английский

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Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Science, Journal Year: 2024, Volume and Issue: 383(6680)

Published: Jan. 18, 2024

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis >6500 proteins in 268 longitudinal samples revealed dysregulated activation the complement system, an innate immune protection and homeostasis mechanism, individuals experiencing Covid. Thus, active was characterized by terminal system dysregulation ongoing alternative classical pathways, latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers hemolysis, tissue injury, platelet activation, monocyte-platelet aggregates were Machine learning thromboinflammatory as top biomarkers, warranting diagnostic therapeutic interrogation these systems.

Language: Английский

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Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

Science Immunology, Journal Year: 2021, Volume and Issue: 6(59)

Published: May 13, 2021

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement is a broad indicator critical illness (and thus, no different COVID-19). It also unclear which pathways are contributing COVID-19, and if associated with certain features infection, such as endothelial injury hypercoagulability. To address these questions, we investigated plasma from patients COVID-19 prospectively enrolled at two tertiary care centers: Washington University School Medicine (n=134) Yale (n=49). We compared our non-COVID cohorts: (a) hospitalized influenza (n=54), (b) admitted intensive unit (ICU) acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). demonstrate that circulating markers elevated those non-COVID-19 failure. Further, results facilitate distinguishing who higher risk worse outcomes ICU admission, or IMV. Moreover, indicate enhanced alternative pathway most prevalent (i.e., angiopoietin-2) well hypercoagulability thrombomodulin von Willebrand factor). Our findings identify distinctive feature provide specific targets may utilized for prognostication, drug discovery personalized clinical trials.

Language: Английский

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