Pathophysiology of infection with SARS‐CoV‐2—What is known and what remains a mystery

Respirology, Journal Year: 2021, Volume and Issue: 26(7), P. 652 - 665

Published: May 26, 2021

Abstract Coronavirus disease 2019 (COVID‐19), caused by coronavirus severe acute respiratory syndrome 2 (SARS‐CoV‐2), has extensive disruption and mortality since its recent emergence. Concomitantly, there been a race to understand the virus pathophysiology. The clinical manifestations of COVID‐19 are manifold not restricted tract. Extrapulmonary involving gastrointestinal tract, hepatobiliary system, cardiovascular renal systems have widely reported. However, pathophysiology many these is controversial with questionable support for direct viral invasion an abundance alternative explanations such as pre‐existing medical conditions critical illness. Prior research on SARS‐Co‐V NL63 was rapidly leveraged identify angiotensin‐converting enzyme (ACE2) receptor key cell surface SARS‐CoV‐2. distribution ACE2 used starting point estimating vulnerability various tissue types SARS‐CoV‐2 infection. Sophisticated organoid animal models demonstrate infectivity extrapulmonary tissues in vitro, but relevance findings remains uncertain. Clinical autopsy studies typically small inevitably biased towards patients prolonged hospitalization. Technical issues delay between time death autopsy, use inappropriate antibodies paraffin‐embedded sections misinterpretation cellular structures particles electron micrograph images additional problems encountered extant literature. Given that likely circulate permanently human populations, no doubt further work required clarify pathobiology COVID‐19.

Language: Английский

---

Acute Kidney Injury in Severe COVID-19 Has Similarities to Sepsis-Associated Kidney Injury

Mayo Clinic Proceedings, Journal Year: 2021, Volume and Issue: 96(10), P. 2561 - 2575

Published: July 15, 2021

To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic proteomic characteristics of autopsy kidneys were analyzed.Individuals 18 years age older who died from COVID-19 had an performed at Mayo Clinic between April 2020 October included. Morphological evaluation the 17 individuals with was performed. In a subset seven cases postmortem interval less than or equal 20 hours, ultrastructural molecular (targeted transcriptome proteomics analyses tubulointerstitium) evaluated. Molecular compared archived S-AKI nonsepsis causes AKI.The spectrum renal pathology included macrophage-dominant microvascular inflammation (glomerulitis peritubular capillaritis), vascular dysfunction (peritubular capillary congestion endothelial injury), tubular evidence mitochondrial damage. Investigation spatial architecture using novel imaging mass cytometry revealed enrichment CD3+CD4+ T cells in close proximity antigen-presenting cells, macrophage-enriched glomerular interstitial infiltrates, suggesting innate adaptive immune tissue response. Coronavirus AKI S-AKI, as nonseptic AKI, transcriptional pathways involved (apoptosis, autophagy, major histocompatibility complex class I II, type 1 helper cell differentiation). Proteomic pathway analysis showed that lesser extent enriched necroptosis sirtuin-signaling pathways, both regulatory response inflammation. Upregulation ceramide-signaling downregulation oxidative phosphorylation noted.This data highlights similarities suggests may play pivotal role AKI. This allow development diagnostic therapeutic targets.

Language: Английский

---

Inflammatory stress in SARS-COV-2 associated Acute Kidney Injury

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(6), P. 1497 - 1506

Published: Jan. 1, 2021

Increasing clinical evidence shows that acute kidney injury (AKI) is a common and severe complication in critically ill COVID-19 patients.The older age, the severity of infection, ethnicity, history smoking, diabetes, hypertension, cardiovascular disease are risk factor for AKI patients.Of them, inflammation may be key player pathogenesis patients with COVID-19.It highly possible SARS-COV-2 infection trigger activation multiple inflammatory pathways including angiotensin II, cytokine storm such as interleukin-6 (IL-6), C-reactive protein (CRP), TGF-β signaling, complement activation, lung-kidney crosstalk to cause AKI.Thus, treatments by targeting these molecules monoclonal antibody against IL-6 (Tocilizumab), C3 inhibitor AMY-101, anti-C5 antibody, anti-TGF-β OT-101, use CRRT represent novel specific therapies patients.

Language: Английский

---

SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis

Immune Network, Journal Year: 2023, Volume and Issue: 23(3)

Published: Jan. 1, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage mortality. High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by stimuli, including viral infections, its secretion levels are related a variety inflammatory diseases. Here, aim study was show SARS-CoV-2 induced HMGB1 via active passive release. Active mediated post-translational modifications, such as acetylation, phosphorylation, oxidation in HEK293E/ACE2-C-GFP Calu-3 cells during infection. Passive has been linked various types death; however, we demonstrated for first time PANoptosis, which integrates other death pathways, pyroptosis, apoptosis, necroptosis, In addition, cytoplasmic translocation extracellular or were confirmed immunohistochemistry immunofluorescence lung tissues humans angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Language: Английский

---

PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute Kidney Injury

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 1, 2021

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) modulating systemic and tissue swine model LPS-induced AKI. After 3 h from LPS infusion, animals underwent PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition terminal complement mediator C5b-9 Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas Complement was assessed by ELISA assay. Gene expression profile performed isolated peripheral blood mononuclear cells (PBMC) microarrays results validated Real-time PCR. Endotoxemic pigs presented oliguric AKI increased tubulo-interstitial infiltrate, extensive collagen deposition, glomerular thrombi; local PTX-3 renal serum classical alternative pathways found endotoxemic animals. treatment significantly reduced limiting fibrosis. By microarray analysis, identified 711 913 differentially expressed genes fold change >2 false discovery rate <0.05 treated-animals, respectively. The most modulated Granzyme B, Factor Component 4 Binding Protein Alpha, IL-12, SERPINB-1 that closely related sepsis-induced immunological process. Our data suggest PMMA-based CVVH can efficiently modulate dysfunction

Language: Английский

---

Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome

Mediators of Inflammation, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 17

Published: April 6, 2022

In recent decades, many serious respiratory infections have broken out all over the world, including SARS-CoV, MERS, and COVID-19. They are characterized by strong infectivity, rapid disease progression, high mortality, poor prognosis. Excessive immune system activation results in cytokine hypersecretion, which is an important reason for aggravation of symptoms, can spread throughout body leading to systemic multiple organ dysfunction, namely, release syndrome (CRS). Although diseases related CRS been identified, mechanism rarely mentioned clearly. This review intended clarify pathogenetic deterioration diseases, describe signaling pathways clinical pathophysiological characteristics CRS, provide ideas further research development specific drugs corresponding targets treat CRS.

Language: Английский

---

Acute Kidney Injury in Kidney Transplant Patients in Intensive Care Unit: From Pathogenesis to Clinical Management

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1474 - 1474

Published: May 18, 2023

Kidney transplantation is the first-choice treatment for end-stage renal disease (ESRD). transplant recipients (KTRs) are at higher risk of experiencing a life-threatening event requiring intensive care unit (ICU) admission, mainly in late post-transplant period (more than 6 months after transplantation). Urosepsis and bloodstream infections account almost half ICU admissions this population; addition, potential side effects related to immunosuppressive should be accounted cytotoxic ischemic changes induced by calcineurin inhibitor (CNI), sirolimus/CNI-induced thrombotic microangiopathy posterior reversible encephalopathy syndrome. Throughout stay, Acute Injury (AKI) incidence common ranges from 10% 80%, up 40% will require replacement therapy. In-hospital mortality can reach 30% correlates with acute illness severity admission diagnosis. Graft survival subordinated baseline estimated glomerular filtration rate (eGFR), clinical presentation, drug nephrotoxicity. The present review aims define impact AKI events on short- long-term outcomes KTRs, focusing epidemiologic data regarding subpopulation; pathophysiological mechanisms underlying development biomarkers kidney transplantation, graft patients’ outcomes; current diagnostic work management AKI; modulation immunosuppression ICU-admitted KTRs.

Language: Английский

---

Klotho protein: A key modulator of aging and COVID-19 severity

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139234 - 139234

Published: Jan. 1, 2025

Language: Английский

---

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

Expert Review of Respiratory Medicine, Journal Year: 2021, Volume and Issue: 15(10), P. 1347 - 1354

Published: April 22, 2021

Introduction Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads mortality. Outcomes of patients with COVID-19-related ARDS compared unrelated COVID-19 is not well characterized.

Language: Английский

---

Kidney involvement in multisystem inflammatory syndrome in children: a pediatric nephrologist’s perspective

Clinical Kidney Journal, Journal Year: 2021, Volume and Issue: 14(9), P. 2000 - 2011

Published: April 12, 2021

The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from UK April 2020; since then, cases have been reported worldwide. Renal involvement has seen commonly, ranging 10% to 46%. Kidney following severe acute respiratory coronavirus 2 infection with MIS-C is more common than initially thought and associated higher morbidity mortality. There are several reports a direct viral tropism disease 2019 MIS-C-associated renal damage. This study's objective systematically review current understanding kidney suffering MIS-C. Based on our systemic literature search, 19 studies either partially or fully discussed patients. Furthermore, we discuss multifactorial pathogenesis contributing injury (AKI) development gives pediatric nephrologist's perspective MIS-C, incidence AKI, pathophysiology AKI proposed therapeutic regimens available, including need for replacement therapy child As rapidly evolving, detailed clinical prospective required understand its role better.

Language: Английский

---