Coronavirus biology and replication: implications for SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 19(3), P. 155 - 170

Published: Oct. 28, 2020

The SARS-CoV-2 pandemic and its unprecedented global societal economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into human population. Although previous SARS-CoV MERS-CoV epidemics raised awareness need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. development effective intervention strategies relies on knowledge molecular cellular mechanisms infections, which highlights significance studying virus-host interactions at level identify targets antiviral elucidate critical viral host determinants that decisive severe disease. In this Review, we summarize first discoveries shape our current understanding infection throughout intracellular life cycle relate biology. elucidation similarities differences between other coronaviruses will support future preparedness combat infections.

Language: Английский

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Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

The Lancet, Journal Year: 2020, Volume and Issue: 396(10250), P. 535 - 544

Published: July 6, 2020

Language: Английский

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Management of post-acute covid-19 in primary care

BMJ, Journal Year: 2020, Volume and Issue: unknown, P. m3026 - m3026

Published: Aug. 11, 2020

What you need to know• Management of covid-19 after the first three weeks is currently based on limited evidence • Approximately 10% people experience prolonged illness Many such patients recover spontaneously (if slowly) with holistic support, rest, symptomatic treatment, and gradual increase in activity Home pulse oximetry can be helpful monitoring breathlessness Indications for specialist assessment include clinical concern along respiratory, cardiac, or neurological symptoms that are new, persistent, progressive

Language: Английский

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Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

Science, Journal Year: 2020, Volume and Issue: 369(6508)

Published: July 15, 2020

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry analyze 125 COVID-19 patients and compare them with recovered healthy individuals. Integrated analysis of ~200 ~50 clinical features revealed activation T cell B subsets in proportion patients. A subgroup had characteristic acute viral infection plasmablast reaching >30% circulating cells. However, another lymphocyte comparable that uninfected Stable versus dynamic immunological signatures were identified linked trajectories severity change. Our analyses three immunotypes associated poor improving health. These may have implications for design therapeutics vaccines COVID-19.

Language: Английский

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COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(9), P. 543 - 558

Published: July 20, 2020

Language: Английский

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Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

The Lancet, Journal Year: 2020, Volume and Issue: 396(10249), P. 479 - 488

Published: July 20, 2020

This is the first randomised controlled trial for assessment of immunogenicity and safety a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose vaccine efficacy study.This randomised, double-blind, placebo-controlled, phase 2 Ad5-vectored was done in single centre Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative previous severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection-free, eligible participate randomly assigned receive at 1 × 1011 viral particles per mL 5 1010 mL, placebo. Investigators allocated participants ratio 2:1:1 injection intramuscularly arm. The randomisation list (block size 4) generated by independent statistician. Participants, investigators, staff undertaking laboratory analyses masked group allocation. primary endpoints geometric mean titres (GMTs) specific ELISA antibody responses receptor binding domain (RBD) neutralising day 28. endpoint evaluation incidence adverse reactions within 14 days. All recruited received least one included analyses. study registered with ClinicalTrials.gov, NCT04341389.603 volunteers screened eligibility between April 11 16, 2020. 508 (50% male; age 39·7 years, SD 12·5) consented (1 n=253; n=129) placebo (n=126). In groups, RBD-specific antibodies peaked 656·5 (95% CI 575·2-749·2) 571·0 (467·6-697·3), seroconversion rates 96% 93-98) 97% (92-99), respectively, Both doses induced significant live SARS-CoV-2, GMTs 19·5 16·8-22·7) 18·3 (14·4-23·3) receiving particles, respectively. Specific interferon γ enzyme-linked immunospot assay post vaccination observed 227 (90%, 95% 85-93) 253 113 (88%, 81-92) 129 Solicited reported 183 (72%) 96 (74%) Severe 24 (9%) (1%) participant group. No serious documented.The safe, immune majority recipients after immunisation.National Key R&D Programme China, National Science Technology Major Project, CanSino Biologics.

Language: Английский

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Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

Gut, Journal Year: 2021, Volume and Issue: 70(4), P. 698 - 706

Published: Jan. 11, 2021

Although COVID-19 is primarily a respiratory illness, there mounting evidence suggesting that the GI tract involved in this disease. We investigated whether gut microbiome linked to disease severity patients with COVID-19, and perturbations composition, if any, resolve clearance of SARS-CoV-2 virus.In two-hospital cohort study, we obtained blood, stool patient records from 100 laboratory-confirmed infection. Serial samples were collected 27 up 30 days after SARS-CoV-2. Gut compositions characterised by shotgun sequencing total DNA extracted stools. Concentrations inflammatory cytokines blood markers measured plasma.Gut composition was significantly altered compared non-COVID-19 individuals irrespective had received medication (p<0.01). Several commensals known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale bifidobacteria underrepresented remained low resolution. Moreover, perturbed exhibited stratification concordant elevated concentrations C reactive protein, lactate dehydrogenase, aspartate aminotransferase gamma-glutamyl transferase.Associations between microbiota levels suggest magnitude possibly via modulating host immune responses. Furthermore, dysbiosis resolution could contribute persistent symptoms, highlighting need understand how microorganisms are inflammation COVID-19.

Language: Английский

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Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19

Allergy, Journal Year: 2020, Volume and Issue: 75(7), P. 1564 - 1581

Published: May 12, 2020

As a zoonotic disease that has already spread globally to several million human beings and possibly domestic wild animals, eradication of coronavirus 2019 (COVID-19) appears practically impossible. There is pressing need improve our understanding the immunology this contain pandemic by developing vaccines medicines for prevention treatment patients. In review, we aim on immune response immunopathological changes in patients linked deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings acute-phase reactants, serum biochemistry COVID-19. Similar many other viral infections, asymptomatic present significant but currently unknown fraction affected individuals. majority patients, 1-week, self-limiting typically occurs, which ends with development neutralizing antiviral T cell antibody immunity. The IgM-, IgA-, IgG-type virus-specific antibodies levels are important measurements predict population immunity against whether cross-reactivity coronaviruses taking place. High load during first infection repeated exposure virus especially healthcare workers can be an factor severity disease. It should noted aspects severe unique COVID-19 rarely observed lymphopenia eosinopenia, extensive pneumonia lung tissue damage, storm leading multiorgan failure. Lymphopenia causes defect regulatory At same time, starts activation cytokine-secreting cells innate adaptive mechanisms both contribute poor prognosis. Elevated reactants early predictors high severity. Prevention disease, novel approaches prevent their will main routes future research areas. learn live amidst virus, assist containing treat individual

Language: Английский

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CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Dec. 4, 2020

Abstract In face of the everlasting battle toward COVID-19 and rapid evolution SARS-CoV-2, no specific effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor mediates virus infection by binding to spike protein. Although ACE2 is expressed in lung, kidney, intestine, its expressing levels are rather low, especially lung. Considering great infectivity COVID-19, we speculate that SARS-CoV-2 may depend on other routes facilitate infection. Here, first discover an interaction between host cell CD147 The loss or blocking Vero E6 BEAS-2B lines anti-CD147 antibody, Meplazumab, inhibits amplification. Expression human allows entry into non-susceptible BHK-21 cells, which can be neutralized extracellular fragment. Viral loads detectable lungs (hCD147) mice infected with but not those virus-infected wild type mice. Interestingly, virions observed lymphocytes lung tissue from patient. Human T cells property natural deficiency pseudovirus dose-dependent manner, specifically inhibited Meplazumab. Furthermore, entering endocytosis. Together, our study reveals novel route, CD147-spike protein, provides important target developing drug against COVID-19.

Language: Английский

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Individuals with obesity and COVID‐19: A global perspective on the epidemiology and biological relationships

Obesity Reviews, Journal Year: 2020, Volume and Issue: 21(11)

Published: Aug. 26, 2020

The linkage of individuals with obesity and COVID-19 is controversial lacks systematic reviews. After a search the Chinese English language literature on COVID-19, 75 studies were used to conduct series meta-analyses relationship obesity-COVID-19 over full spectrum from risk mortality. A review mechanistic pathways for presented. Pooled analysis show more at positive, >46.0% higher (OR = 1.46; 95% CI, 1.30-1.65; p < 0.0001); hospitalization, 113% 2.13; 1.74-2.60; ICU admission, 74% 1.74; 1.46-2.08); mortality, 48% increase in deaths 1.48; 1.22-1.80; 0.001). Mechanistic are presented depth factors linked risk, severity their potential diminished therapeutic prophylactic treatments among these individuals. Individuals large significant increases morbidity mortality COVID-19. There many mechanisms that jointly explain this impact. major concern vaccines will be less effective obesity.

Language: Английский

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