Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

EClinicalMedicine, Год журнала: 2021, Номер 31, С. 100683 - 100683

Опубликована: Янв. 1, 2021

BackgroundThe medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality life and mental health are poorly understood.MethodsFifty-eight COVID-19 patients post-hospital discharge 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary test (CPET), life, cognitive assessments.FindingsAt 2–3 months from disease-onset, 64% experienced breathlessness 55% reported fatigue. On MRI, abnormalities seen in lungs (60%), heart (26%), (10%) kidneys (29%). Patients exhibited changes the thalamus, posterior thalamic radiations sagittal stratum brain MRI demonstrated impaired performance, specifically executive visuospatial domains. Exercise tolerance (maximal oxygen consumption ventilatory efficiency CPET) distance significantly reduced. The extent extra-pulmonary intolerance correlated with serum markers inflammation acute illness severity. had a higher burden self-reported symptoms depression significant impairment all domains compared to (p<0.0001 0.044).InterpretationA proportion discharged hospital breathlessness, fatigue, limited capacity. Persistent lung findings common linked severity illness.FundingNIHR Oxford Health Biomedical Research Centres, British Heart Foundation Centre Excellence, UKRI, Wellcome Trust, Foundation.

Язык: Английский

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The signal pathways and treatment of cytokine storm in COVID-19

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Июль 7, 2021

Abstract The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It affected significant proportion of the population both physically mentally, destroyed businesses societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation monocytes macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, especially, cytokine storm (CS). CS characterized by hyperproduction an array pro-inflammatory cytokines closely associated with poor prognosis. These excessively secreted initiate different inflammatory signaling pathways via their receptors on immune tissue cells, resulting in complicated medical symptoms fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress multiorgan failure, ultimately leading to death most severe cases. Therefore, it clinically important understand initiation develop effective treatment strategies COVID-19. Herein, we discuss latest developments immunopathological characteristics focus current research status involved. We also induction, function, downstream signaling, existing potential interventions targeting these related signal pathways. believe comprehensive understanding will help better effectively control this disease diseases.

Язык: Английский

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COVID-19 vaccines: The status and perspectives in delivery points of view

Advanced Drug Delivery Reviews, Год журнала: 2020, Номер 170, С. 1 - 25

Опубликована: Дек. 24, 2020

Язык: Английский

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COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies

European Journal of Pharmacology, Год журнала: 2020, Номер 892, С. 173751 - 173751

Опубликована: Ноя. 24, 2020

Язык: Английский

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Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

Frontiers in Medicine, Год журнала: 2020, Номер 7

Опубликована: Дек. 3, 2020

The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought role angiotensin converting enzyme 2 (ACE2) back into scientific limelight. Since SARS-CoV-2 must bind ACE2 for entering host cells in humans, its expression and body localization are critical to track potential target organ this infection outline disease progression clinical outcomes. Here, we mapped physiological distribution, expression, activities discussed correlations mutal interactions with disparate symptoms present patients at level different organs. We highlighted that despite during ACE2-expressing organs may become direct targets, leading severe pathological manifestations, subsequent multiple failures, exact mechanism through which acts these is still heavily debated. Further efforts, also considering a personalized approach aimed consider specific patient differences mutual ACE2-SARS-CoV-2 long-term health effects associated COVID-19 currently mandatory.

Язык: Английский

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Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19

Critical Care, Год журнала: 2020, Номер 24(1)

Опубликована: Дек. 1, 2020

Abstract Background COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in samples but also blood, stool urine. Severe characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or load plasma associated severe response. Methods A total of 250 patients were recruited (50 outpatients, 100 hospitalized ward critically ill). Viral detection quantification was performed using droplet digital PCR, targeting the N1 N2 regions nucleoprotein gene. The association between severity evaluated multivariate logistic regression. Correlations biomarkers evidencing dysregulation calculating Spearman correlation coefficients. Results frequency higher ill (78%) compared (27%) outpatients (2%) ( p < 0.001). Critical had loads than non-critically patients, non-survivors showing highest values. When compared, did not show significant associations analysis. In contrast, when ICU both critical illness (OR [CI 95%], ): (3.92 [1.183–12.968], 0.025), (N1) (1.962 [1.244–3.096], 0.004); (N2) (2.229 [1.382–3.595], correlated levels chemokines (CXCL10, CCL2), indicative systemic inflammatory (IL-6, CRP, ferritin), activation NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation (D-Dimer INR), tissue damage (LDH, GPT), neutrophil (neutrophils counts, myeloperoxidase, GM-CSF) immunodepression (PD-L1, IL-10, lymphopenia monocytopenia). Conclusions are COVID-19. correlates key signatures responses, suggesting major role uncontrolled replication pathogenesis

Язык: Английский

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Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management

Drug Discovery Today, Год журнала: 2021, Номер 26(11), С. 2619 - 2636

Опубликована: Июль 29, 2021

Язык: Английский

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DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

PLoS Pathogens, Год журнала: 2021, Номер 17(5), С. e1009576 - e1009576

Опубликована: Май 20, 2021

The efficient spread of SARS-CoV-2 resulted in a unique pandemic modern history. Despite early identification ACE2 as the receptor for viral spike protein, much remains to be understood about molecular events behind dissemination. We evaluated contribution C-type lectin receptors (CLRS) antigen-presenting cells, widely present respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin MGL bind diverse glycans using multiple interaction areas. Using pseudovirus cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote transfer permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against enable inhibition this process. These data have been then confirmed authentic human lines. Thus, described mechanism potentiating spreading infection.

Язык: Английский

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A time-resolved proteomic and prognostic map of COVID-19

Cell Systems, Год журнала: 2021, Номер 12(8), С. 780 - 794.e7

Опубликована: Июнь 14, 2021

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of disease 139 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts enzyme activities, well untargeted plasma proteomes at 687 sampling points. report an initial spike a systemic inflammatory response, which gradually alleviated followed protein signature indicative tissue repair, metabolic reconstitution, immunomodulation. identify prognostic marker signatures for devising risk-adapted treatment strategies use machine learning classify therapeutic needs. show that models based on proteome are transferable independent cohort. Our study presents map linking routinely used parameters their dynamics infectious disease.

Язык: Английский

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Neutrophils and COVID-19: The road so far

International Immunopharmacology, Год журнала: 2020, Номер 90, С. 107233 - 107233

Опубликована: Ноя. 30, 2020

Язык: Английский

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