Kidney360, Год журнала: 2021, Номер 3(1), С. 28 - 36
Опубликована: Ноя. 5, 2021
AKI is a common sequela of infection with SARS-CoV-2 and contributes to the severity mortality from COVID-19. Here, we tested hypothesis that kidney alterations induced by COVID-19-associated could be detected in cells collected urine.
Язык: Английский
Bioscience Reports, Год журнала: 2021, Номер 41(8)
Опубликована: Июль 30, 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One most important pathologies, hypercoagulation and microclots in lungs patients. Here we study effect isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron fluorescence microscopy well mass spectrometry, investigate this to interact with platelets fibrin(ogen) directly blood hypercoagulation. platelet-poor plasma (PPP), show that may interfere flow. Mass spectrometry also showed when added healthy PPP, it results structural changes β γ fibrin(ogen), complement 3, prothrombin. These proteins were substantially resistant trypsinization, presence S1. suggest that, part, circulation contribute COVID-19 positive patients substantial impairment fibrinolysis. Such lytic result persistent large have noted here previously samples This observation relevance treatment hypercoagulability
Язык: Английский
Процитировано
163
Clinical Science, Год журнала: 2021, Номер 135(24), С. 2667 - 2689
Опубликована: Ноя. 22, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. capacity SARS-CoV-2 to infect vascular cells is still debated. Additionally, the Spike (S) protein may act as ligand induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced heart patients with disease-2019 (COVID-19). Here we newly show that vitro exposure primary human cardiac PCs wildtype strain or α and δ variants caused rare infection events. Exposure recombinant S alone elicited signalling functional alterations, including: (1) increased migration, (2) ability support endothelial cell (EC) network formation on Matrigel, (3) secretion pro-inflammatory molecules typically involved cytokine storm, (4) production pro-apoptotic factors causing EC death. Next, adopting blocking strategy against receptors angiotensin-converting enzyme (ACE2) CD147, discovered stimulates phosphorylation/activation extracellular signal-regulated kinase 1/2 (ERK1/2) through CD147 receptor, but not ACE2, PCs. neutralisation either using antibody mRNA silencing, ERK1/2 activation, rescued PC function presence protein. Immunoreactive was detected peripheral blood infected patients. In conclusion, our findings suggest prompt dysfunction, potentially contributing injury. This mechanism have therapeutic implications.
Язык: Английский
Процитировано
82
Clinical Journal of the American Society of Nephrology, Год журнала: 2021, Номер 16(11), С. 1755 - 1765
Опубликована: Июнь 14, 2021
Despite evidence of multiorgan tropism severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question whether SARS-CoV2 can directly infect the is relevant understanding pathogenesis AKI and collapsing glomerulopathy COVID-19. Methodologies document SARS-CoV-2 infection that have used include immunohistochemistry, immunofluorescence, RT-PCR, situ hybridization, electron microscopy. In our review studies date, we found kidneys COVID-19 was detected 18 94 (19%) by 71 144 (49%) 11 84 (13%) hybridization. a smaller number examined 10 13 (77%). total, from 102 235 (43%), presence suggested at least one methods used. these positive findings, caution needed because many other negative for it should be noted when detected, only obtained autopsy. There clear need biopsies, including those performed early stages COVID-19–associated disease. Development tests detect urine samples would more practical as noninvasive way evaluate during evolution
Язык: Английский
Процитировано
68
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Дек. 9, 2022
Abstract Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well in distal organs. While it appreciated that an exaggerated inflammatory response dysfunction, triggers of vascular leak are unclear. Here, we report cell-intrinsic interactions between Spike (S) glycoprotein SARS-CoV-2 epithelial/endothelial cells sufficient to induce vitro vivo, independently viral replication ACE2 receptor. We identify S-triggered transcriptional extracellular matrix reorganization TGF-β signaling. Using genetic knockouts specific inhibitors, demonstrate glycosaminoglycans, integrins, signaling axis required for S-mediated dysfunction. Notably, show infection caused which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered leak, providing a starting point development therapies targeting COVID-19.
Язык: Английский
Процитировано
53
Kidney International Reports, Год журнала: 2023, Номер 8(6), С. 1137 - 1150
Опубликована: Март 27, 2023
Язык: Английский
Процитировано
29
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Апрель 5, 2023
ABSTRACT Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and tissue loss, raising concerns about virus’s potential chronic impact on central nervous system. In this study, we utilized mouse models human post-mortem tissues to investigate presence distribution SARS-CoV-2 spike protein in skull-meninges-brain axis. Our results revealed accumulation skull marrow, meninges, parenchyma. The injection alone cell death brain, highlighting direct effect tissue. Furthermore, observed deceased long after their COVID-19 infection, suggesting that spike’s persistence may contribute long-term symptoms. was neutrophil-related pathways dysregulation proteins involved PI3K-AKT as well complement coagulation pathway. Overall, our findings suggest trafficking from CNS borders into parenchyma identified differentially regulated present insights mechanisms underlying immediate consequences diagnostic therapeutic opportunities. Graphical Summary Short axis presents molecular targets for complications long-COVID-19 patients .
Язык: Английский
Процитировано
26
International Urology and Nephrology, Год журнала: 2021, Номер 54(1), С. 17 - 21
Опубликована: Ноя. 17, 2021
Язык: Английский
Процитировано
34
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12585 - 12585
Опубликована: Авг. 9, 2023
COVID-19 progression often involves severe lung injury, inflammation, coagulopathy, and leukocyte infiltration into pulmonary tissues. The pathogenesis of these complications is unknown. Because vascular endothelium neutrophils express angiotensin-converting enzyme-2 spike (S)-proteins, which are present in bodily fluids tissues SARS-CoV-2-infected patients, we investigated the effect S-proteins cell-cell communication on human microvascular endothelial cells expression P-selectin, markers NETosis, inflammation. Exposure or to endothelial-neutrophils co-culture induced P-selectin transcription expression, significantly increased expression/secretion IL-6, von Willebrand factor (vWF, pro-coagulant), citrullinated histone H3 (cit-H3, NETosis marker). Compared SARS-CoV-2 Wuhan variant, Delta variant 1.4-15-fold higher IL-6 vWF. Recombinant tissue pathway inhibitor (rTFPI), 5,5'-dithio-bis-(2-nitrobenzoic acid) (thiol blocker), thrombomodulin (anticoagulant) blocked S-protein-induced vWF, cit-H3. This suggests that following contact with endothelial-neutrophil interactions, increase adhesion molecules, induce coagulopathy via pathway, mechanisms involving functional thiol groups, and/or fibrinolysis system. Using rTFPI, effectors system thiol-based drugs could be viable therapeutic strategies against SARS-CoV-2-induced coagulopathy.
Язык: Английский
Процитировано
15
Brain Behavior and Immunity, Год журнала: 2024, Номер 121, С. 87 - 103
Опубликована: Июль 21, 2024
Язык: Английский
Процитировано
6
Molecular Neurobiology, Год журнала: 2022, Номер 59(10), С. 6076 - 6090
Опубликована: Июль 20, 2022
Язык: Английский
Процитировано
23