The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(5), P. 358 - 368

Published: March 3, 2022

Language: Английский

---

Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes

Clinical Infectious Diseases, Journal Year: 2021, Volume and Issue: 74(9), P. 1525 - 1533

Published: Aug. 9, 2021

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with disease 2019 (COVID-19), but it not clear whether this RNAemia reflects viremia (ie, virus particles) and how relates to host immune responses outcomes. Methods SARS-CoV-2 vRNA was quantified plasma samples from observational cohorts 51 COVID-19 including 9 outpatients, 19 hospitalized (non–intensive care unit [ICU]), 23 ICU patients. levels were compared cross-sectional indices severity prospective clinical We used multiple imaging methods visualize virions plasma. Results 100%, 52.6%, 11.1% ICU, non-ICU, respectively. Virions pellets using electron tomography immunostaining. Plasma significantly higher > non-ICU outpatients (P < .0001); for inpatients, strongly associated World Health Organization (WHO) score at admission = .01), maximum WHO .002), discharge disposition .004). A level >6000 copies/mL mortality (hazard ratio, 10.7). Levels several inflammatory biomarkers .01) neutralizing antibody titers .8). Conclusions Visualization particles indicates that due, least part, viremia. The correlate severity, patient outcome, specific titers.

Language: Английский

---

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Feb. 15, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 not only restricted to infecting tract, but virus also found other tissues, including vasculature. Individuals with underlying pre-existing co-morbidities like diabetes hypertension have been more prone develop severe illness fatal outcomes COVID-19. In addition, critical clinical observations made COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, endothelial dysfunction, which are indicative for an involvement vasculature pathology. Hence, review summarizes impact infection details how promotes (chronic) vascular inflammation. We provide general overview SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) detection extrapulmonary tissue. Further, we describe relation between cardiovascular diseases (CVD) their Clinical findings changes reviewed detail recent evidence from vitro studies susceptibility cells discussed. conclude current notions contribution events long term consequences COVID-19, known “Long-COVID-syndrome”. Altogether, our provides detailed perspectives influence

Language: Английский

---

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 400 - 400

Published: Jan. 31, 2023

A novel syndrome called long-haul COVID or long is increasingly recognized in a significant percentage of individuals within few months after infection with SARS-CoV-2. This disorder characterized by wide range persisting, returning even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine systemic. Some overlapping symptomatologies exist between myalgic encephalomyelitis/chronic fatigue (ME/CFS). Very much like ME/CFS, infections herpes family viruses, immune dysregulation, the persistence inflammation have been reported as most common pattern for development COVID. review describes several factors determinants proposed, elaborating mainly on viral persistence, reactivation latent viruses such Epstein–Barr virus human herpesvirus 6 which are also associated pathology superantigen activation system, disturbance gut microbiome, multiple tissue damage autoimmunity. Based these factors, we propose diagnostic strategies measurement IgG IgM antibodies against SARS-CoV-2, EBV, HHV-6, superantigens, microbiota, biomarkers autoimmunity to better understand manage this multi-factorial continues affect millions people world.

Language: Английский

---

SARS-CoV-2 placentitis, stillbirth, and maternal COVID-19 vaccination: clinical–pathologic correlations

American Journal of Obstetrics and Gynecology, Journal Year: 2022, Volume and Issue: 228(3), P. 261 - 269

Published: Oct. 12, 2022

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection the placenta. Multiple global studies have found placental pathology present cases stillbirth consists combination concurrent destructive findings include increased fibrin deposition typically reaches level massive perivillous deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed placentitis, can cause severe diffuse parenchymal destruction affect >75% placenta, effectively rendering it incapable performing its function oxygenating fetus leading neonatal death via malperfusion insufficiency. Placental occur absence demonstrable fetal infection. Development placentitis complex process may both an infectious immunologic basis. An important observation all reported causing death, mothers were unvaccinated. likely result episode viremia at some time during pregnancy. This article discusses clinical aspects relationship between maternal vaccination, perinatal death.

Language: Английский

---

Post-acute sequelae of COVID-19: A metabolic perspective

eLife, Journal Year: 2022, Volume and Issue: 11

Published: March 23, 2022

The SARS-CoV-2 pandemic continues to rage around the world. At same time, despite strong public health measures and high vaccination rates in some countries, a post-COVID-19 syndrome has emerged which lacks clear definition, prevalence, or etiology. However, fatigue, dyspnea, brain fog, lack of smell and/or taste are often characteristic patients with this syndrome. These evident more than month after infection, labeled as Post-Acute Sequelae CoV-2 (PASC) commonly referred long-COVID. Metabolic dysfunction (i.e., obesity, insulin resistance, diabetes mellitus) is predisposing risk factor for severe acute COVID-19, there emerging evidence that plus chronic inflammatory state may predispose PASC. In article, we explore potential pathogenic metabolic mechanisms could underly both COVID-19 PASC, then consider how these might be targeted future therapeutic approaches.

Language: Английский

---

Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2021, Volume and Issue: 205(5), P. 507 - 519

Published: Dec. 8, 2021

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar dynamics associations COVID-19 severity, cardiorenovascular injury, outcomes. Methods: This single-center observational study enrolled patients requiring respiratory support at emergency department presentation. More than 40 markers of (including receptor for advanced glycation endproducts [RAGE]), angiopoietin-2), renin, kidney molecule-1, troponin-I) were serially compared between invasively spontaneously ventilated using mixed-effects repeated-measures models. Ventilatory ratios calculated intubated patients. Associations biomarkers modified World Health Organization scale Day 28 determined multivariable proportional-odds regression. Measurements Main Results: Of 225 patients, 74 (33%) received invasive ventilation 0. RAGE was 1.80-fold higher in 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased time all Changes did not correlate changes endothelial, cardiac, or renal markers. In contrast, similar to lower then increased only among angiopoietin-2 (fold difference, 1.02; 95% CI, 0.89-1.17) nonintubated 1.56-2.06) 3; showed patterns. Endothelial consistently ventilatory ratios. more often significantly 28-day outcomes Conclusions: increase early. later are outcome. likely contribute different times progression severe COVID-19.

Language: Английский

---

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease

Clinical Science, Journal Year: 2021, Volume and Issue: 135(24), P. 2667 - 2689

Published: Nov. 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.

Language: Английский

---

ACE2 Shedding and the Role in COVID-19

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 14, 2022

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In COVID-19 epidemic, it was found to be receptor severe acute respiratory syndrome coronavirus (SARS-COV-2). ACE2 maintains homeostasis by inhibiting Ang II-AT1R axis and activating I (1-7)-MasR axis, protecting against lung, heart kidney injury. addition, helps transport amino acids across membrane. sheds from membrane, producing soluble (sACE2). Previous studies have pointed out that sACE2 plays role in pathology disease, but underlying mechanism not yet clear. Recent confirmed can also act as SARS-COV-2, mediating viral entry into cell then spreading infective area. Elevated concentrations are more related disease. Recombinant human ACE2, exogenous used supplement endogenous ACE2. It may represent potent treatment future. However, specific administration concentration needs further investigated.

Language: Английский

---

Immunocompromised Patients with Protracted COVID-19: a Review of “Long Persisters”

Current Transplantation Reports, Journal Year: 2022, Volume and Issue: 9(4), P. 209 - 218

Published: Nov. 12, 2022

Abstract Purpose of Review Certain immunocompromised individuals are at risk for protracted COVID-19, in which SARS-CoV-2 leads to a chronic viral infection. However, the pathogenesis, diagnosis, and management this phenomenon remain ill-defined. Recent Findings Herein, we review key aspects infection individuals, or so-called long persisters, describe clinical presentation, factors, treatment modalities condition, as well intra-host evolution. Based on available data, also propose framework criteria with approach syndrome. Summary Protracted COVID-19 is an uncharacterized syndrome affecting patients B-cell depletion; our proposed diagnostic definitions will inform much needed future research.

Language: Английский

---