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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Humoral Innate Immunity and Acute-Phase Proteins

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(5), P. 439 - 452

Published: Feb. 1, 2023

Language: Английский

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COVID-19 2022 update: transition of the pandemic to the endemic phase

Human Genomics, Journal Year: 2022, Volume and Issue: 16(1)

Published: June 1, 2022

Abstract COVID-19, which is caused by the SARS-CoV-2, has ravaged world for past 2 years. Here, we review current state of research into disease with focus on its history, human genetics and genomics transition from pandemic to endemic phase. We are particularly concerned lack solid information initial phases that highlighted necessity better preparation face similar future threats. On other hand, gratified progress genetic susceptibility investigations believe now time explore The latter will require worldwide vigilance cooperation, especially in emerging countries. In phase, vaccination rates have lagged developed countries should assist, as warranted, bolstering worldwide. also discuss status vaccines outlook COVID-19.

Language: Английский

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Immune response in COVID-19: what is next?

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1107 - 1122

Published: May 17, 2022

Abstract The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle quality in unprecedented ways. A better understanding of immunity its regulation response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here various virus mutations evolving manifestations along with alterations immune responses specific focuses innate response, neutrophil extracellular traps, humoral immunity, cellular immunity. Different types vaccines were compared analyzed based their unique properties elicit Various therapeutic strategies such as antibody, anti-viral medications inflammation control discussed. We predict that available continuously emerging new technologies, powerful administration schedules, effective public health measures, COVID-19 will be under near future.

Language: Английский

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A guide to complement biology, pathology and therapeutic opportunity

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 118 - 141

Published: Sept. 5, 2023

Language: Английский

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Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(639)

Published: March 1, 2022

A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is develop a broadly protective vaccine that elicits long-term immunity. As key immunogen, viral surface spike (S) protein frequently mutated, and conserved epitopes are shielded glycans. Here, we revealed S glycosylation has site-differential effects on infectivity. We found generated lung epithelial cells glycoforms associated with increased Compared fully glycosylated protein, immunization of N-glycans trimmed mono-GlcNAc-decorated state (SMG) elicited stronger immune responses better protection for human angiotensin-converting enzyme (hACE2) transgenic mice against variants concern (VOCs). In addition, neutralizing monoclonal antibody was identified from SMG-immunized could neutralize wild-type SARS-CoV-2 VOCs subpicomolar potency. Together, these results demonstrate removal glycan shields expose sequences potential be an effective simple approach developing vaccine.

Language: Английский

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Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Language: Английский

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Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 14, 2022

Abstract Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but underlying mechanism remains unclear. In this study, N proteins including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east (MERS-CoV) 2 (SARS-CoV-2), were found bind MASP-2, a key serine protease in lectin pathway complement activation, resulting excessive activation by potentiating MBL-dependent MASP-2 deposition C4b, activated C3 C5b-9. Aggravated lung injury was observed mice infected with adenovirus expressing protein. Complement hyperactivation also SARS-CoV-2-infected patients. Either blocking protein:MASP-2 interaction, depletion or suppressing can significantly alleviate protein-induced vitro vivo. Altogether, these data suggested that suppression may represent novel therapeutic approach for pneumonia induced coronaviruses.

Language: Английский

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Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 604 - 611

Published: March 6, 2023

Abstract Infection with severe acute respiratory syndrome coronavirus 2 associates diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors associated adverse disease 2019 (COVID-19) outcomes. Here we discovered that against specific chemokines were omnipresent post-COVID-19, favorable outcome negatively correlated the development of long COVID at 1 yr post-infection. Chemokine also present in HIV-1 infection autoimmune disorders, but they targeted different compared COVID-19. Monoclonal derived from COVID-19 convalescents bound to chemokine N-loop impaired cell migration. Given role orchestrating trafficking, naturally arising may modulate inflammatory response thus bear therapeutic potential.

Language: Английский

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The Lectin Pathway of the Complement System—Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1566 - 1566

Published: Jan. 26, 2024

The complement system is the other major proteolytic cascade in blood of vertebrates besides coagulation–fibrinolytic system. Among three main activation routes complement, lectin pathway (LP) has been discovered latest, and it still subject intense research. Mannose-binding (MBL), collectins, ficolins are collectively termed as pattern recognition molecules (PRMs) LP, they responsible for targeting LP to molecular patterns, e.g., on bacteria. MBL-associated serine proteases (MASPs) effectors, while proteins (MAps) have regulatory functions. Two protease components, MASP-1 MASP-2, trigger activation, third component, MASP-3, involved function alternative (AP) complement. Besides their functions within system, certain components secondary (“moonlighting”) functions, embryonic development. They also contribute coagulation, some might tumor suppressing roles. Uncontrolled can progression many diseases (e.g., stroke, kidney diseases, thrombotic complications, COVID-19). In most cases, implicated. this review, we summarize history pathway, introduce describe its regulation, roles cascade, connections direct cellular effects. Special emphasis placed disease non-canonical components.

Language: Английский

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