SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(664)

Published: June 7, 2022

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying COVID biology, we compared short- and long-term systemic responses golden hamster after either SARS-CoV-2 influenza A virus (IAV) infection. Results demonstrated that exceeded IAV its capacity cause permanent injury lung kidney uniquely affected olfactory bulb (OB) epithelium (OE). Despite a lack detectable infectious virus, OB OE myeloid T cell activation, proinflammatory cytokine production, an interferon correlated with behavioral changes extending month viral clearance. These sustained transcriptional could also be corroborated from tissue isolated individuals who recovered COVID-19. data highlight molecular for persistent symptomology provide small animal model explore future therapeutics.

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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JAK inhibitor blocks COVID-19 cytokine–induced JAK/STAT/APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids

JCI Insight, Journal Year: 2022, Volume and Issue: 7(11)

Published: April 26, 2022

COVID-19 infection causes collapse of glomerular capillaries and loss podocytes, culminating in a severe kidney disease called COVID-19–associated nephropathy (COVAN). The underlying mechanism COVAN is unknown. We hypothesized that cytokines induced by trigger expression pathogenic APOL1 via JAK/STAT signaling, resulting podocyte phenotype. Here, based on 9 biopsy-proven cases, we demonstrated for the first time, to best our knowledge, protein was abundantly expressed podocytes endothelial cells (GECs) kidneys but not controls. Moreover, majority patients with carried 2 risk alleles. show recombinant SARS-CoV-2 acted synergistically drive through pathway primary human GECs, micro-organoids derived from carrier alleles, blocked JAK1/2 inhibitor, baricitinib. demonstrate cytokine-induced JAK/STAT/APOL1 signaling reduced viability organoid rescued Together, results support conclusion COVID-19–induced are sufficient COVAN-associated podocytopathy JAK inhibitors could block this process. These findings suggest may have therapeutic benefits managing cytokine-induced, APOL1-mediated podocytopathy.

Language: Английский

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Podocyte-targeted therapies — progress and future directions

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(10), P. 643 - 658

Published: May 9, 2024

Language: Английский

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Longitudinal Outcomes of COVID-19–Associated Collapsing Glomerulopathy and Other Podocytopathies

Journal of the American Society of Nephrology, Journal Year: 2021, Volume and Issue: 32(11), P. 2958 - 2969

Published: Oct. 20, 2021

The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown.We retrospectively identified 76 native kidney biopsies from patients with history COVID-19 between March 2020 and April 2021. Presenting data were obtained for all 23 seven noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining spike nucleocapsid proteins, in situ hybridization SARS-CoV-2.The median age 57 years (range, 35-72), included 16 men, predominantly (91%) Black. Severity was mild or moderate most (77%) patients. All but one patient presented AKI, 17 had nephrotic-range proteinuria, six nephrotic syndrome. Fourteen (61%) required dialysis at presentation. Among genotyped, (94%) high-risk APOL1. 22 (96%) follow-up 155 days 30-412), 11 (50%) received treatment COVID-19, eight (36%) glucocorticoid therapy podocytopathy. At follow-up, 19 (86%) alive, 15 (68%) free, including 14 who initially dialysis. dialysis-free 64% (seven 11) those treated 75% (six eight) glucocorticoids Overall, 36% achieved partial remission 32% no remission, reached combined end points ESKD death. Viral infection the not detected.Half requiring independence, prognosis residual proteinuric CKD remains guarded, indicating a need more effective therapy.

Language: Английский

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COVID-19 Survival and its impact on chronic kidney disease

Translational research, Journal Year: 2021, Volume and Issue: 241, P. 70 - 82

Published: Nov. 10, 2021

Up to 87% of patients hospitalized with coronavirus disease 2019 (COVID-19) experience chronic sequelae following infection. The long-term impact COVID-19 infection on kidney function is largely unknown at this point in the pandemic. In review, we highlight current understanding pathophysiology COVID-19-associated injury and may have function. COVID-19-induced acute lead tubular injury, endothelial glomerular injury. We histopathologic correlates from large biopsy autopsy series. By conducting a comprehensive review published literature date, summarize rates recovery COVID-19-associated-AKI. Finally, discuss how certain genetic differences, including APOL1 risk alleles (a factor for collapsing glomerulopathy), coupled systemic healthcare disparities, disproportionate burden post-COVID-19-kidney decline among racial ethnic minority groups. need prospective studies determine true incidence after COVID-19.

Language: Английский

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A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection

Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 33(7), P. 1293 - 1307

Published: March 2, 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme (ACE2) as a main receptor to enter target cells. The goal of this study was demonstrate the preclinical efficacy novel soluble ACE2 protein with increased duration action and binding capacity in lethal mouse model COVID-19.

Language: Английский

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COVID-19 and Kidney Disease

Annual Review of Medicine, Journal Year: 2022, Volume and Issue: 74(1), P. 1 - 13

Published: Sept. 15, 2022

COVID-19 can cause acute kidney injury and may or exacerbate chronic diseases, including glomerular diseases. SARS-CoV-2 infection of cells has been reported, but it remains unclear if viral causes disease. The most important in patients with include impaired renal perfusion immune dysregulation. Chronic disease, especially failure replacement therapy transplant, is associated markedly increased mortality. Persons severe disease have excluded from clinical trials therapies, so therapeutic approaches must be extrapolated studies without Some medications used to treat should avoided at reduced dosages transplant recipients. Additional research needed determine the optimal strategies prevent

Language: Английский

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Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: Jan. 5, 2023

Abstract Background Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated global data set on the demographics, management outcomes critically ill patients. LUNG-SAFE study was an international prospective cohort patients with failure, including ARDS, which pre-dated pandemic. Methods incidence, demographic profile, early AKI in undergoing invasive mechanical ventilation for ARDS were described compared cohort. Results Of 18,964 CCCC set, 1699 required had relevant outcome data. these, 110 (6.5%) stage 1, 94 (5.5%) 2, 151 (8.9%) 3 AKI, while 1214 (79.1%) no within 48 h initiating ventilation. Patients developing older more likely to have hypertension or chronic cardiac disease. There geo-economic differences incidence lower European high-income countries higher from middle-income countries. Both 28-day 90-day mortality risk increased 2 (HR 2.00, p < 0.001) 1.95, 0.001). Compared non-COVID-19 shock reduced cardiovascular SOFA score across all patient groups, hospital worse groups [no (30 vs 50%), Stage 1 (38 58%), (56 74%), (52 72%), 0.001]. time profile onset also differed, 56% occurring first 89% population. Conclusion common serious COVID-19, high rate, differs by location. Important exist versus terms their haemodynamic clinical outcomes.

Language: Английский

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