Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(16), P. 1491 - 1502

Published: Feb. 25, 2021

The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.We evaluated tocilizumab and sarilumab an ongoing international, multifactorial, adaptive platform trial. Adult Covid-19, within 24 hours after starting organ support the intensive care unit (ICU), were randomly assigned to receive (8 mg per kilogram body weight), (400 mg), or standard (control). primary outcome was respiratory cardiovascular support-free days, on ordinal scale combining in-hospital death (assigned a value -1) days free day 21. trial uses Bayesian statistical model predefined criteria for superiority, efficacy, equivalence, futility. An odds ratio greater than 1 represented improved survival, more both.Both met efficacy. At that time, 353 had been tocilizumab, 48 sarilumab, 402 control. median number 10 (interquartile range, -1 16) group, 11 0 15) control group. adjusted cumulative ratios 1.64 (95% credible interval, 1.25 2.14) 1.76 1.17 2.91) as compared control, yielding posterior probabilities superiority 99.9% 99.5%, respectively. analysis 90-day survival showed pooled antagonist groups, hazard comparison group 1.61 2.08) probability 99.9%. All secondary analyses supported these antagonists.In Covid-19 receiving ICUs, treatment outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Language: Английский

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Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

The Lancet, Journal Year: 2021, Volume and Issue: 397(10285), P. 1637 - 1645

Published: April 30, 2021

Language: Английский

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Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ, Journal Year: 2020, Volume and Issue: unknown, P. m2980 - m2980

Published: July 30, 2020

To compare the effects of treatments for coronavirus disease 2019 (covid-19). Living systematic review and network meta-analysis. WHO covid-19 database, a comprehensive multilingual source global literature, up to 3 December 2021 six additional Chinese databases 20 February 2021. Studies identified as 1 were included in analysis. Randomised clinical trials which people with suspected, probable, or confirmed randomised drug treatment standard care placebo. Pairs reviewers independently screened potentially eligible articles. After duplicate data abstraction, bayesian meta-analysis was conducted. Risk bias studies assessed using modification Cochrane risk 2.0 tool, certainty evidence grading recommendations assessment, development, evaluation (GRADE) approach. For each outcome, interventions classified groups from most least beneficial harmful following GRADE guidance. 463 enrolling 166 581 patients included; 267 (57.7%) 89 814 (53.9%) are new previous iteration; 265 (57.2%) evaluating at 100 events met threshold inclusion analyses. Compared care, three drugs reduced mortality mostly severe moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 7 fewer, certainty), interleukin-6 receptor antagonists when given (23 1000, 36 Janus kinase inhibitors (44 64 high certainty). two probably reduce hospital admission non-severe disease: nirmatrelvir/ritonavir (36 41 26 certainty) molnupiravir (19 29 5 Remdesivir may (29 6 low Only had quality reduction time symptom resolution (3.3 days 4.8 1.6 certainty); several others showed possible benefit. Several increase adverse leading discontinuation; hydroxychloroquine increases mechanical ventilation (moderate Corticosteroids, antagonists, confer other important benefits covid-19. Molnupiravir This not registered. The protocol is publicly available supplementary material. article living that will be updated reflect emerging evidence. Updates occur years date original publication. fifth version published on 30 July 2020 (BMJ 2020;370:m2980), versions can found supplements. When citing this paper please consider adding number access clarity.

Language: Английский

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Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19

JAMA, Journal Year: 2021, Volume and Issue: 326(6), P. 499 - 499

Published: July 6, 2021

Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Language: Английский

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Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

The Lancet, Journal Year: 2021, Volume and Issue: 397(10274), P. 605 - 612

Published: Feb. 1, 2021

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 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.

Language: Английский

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COVID-19: breaking down a global health crisis

Annals of Clinical Microbiology and Antimicrobials, Journal Year: 2021, Volume and Issue: 20(1)

Published: May 18, 2021

Abstract Coronavirus disease 2019 (COVID-19) is the second pandemic of twenty-first century, with over one-hundred million infections and two deaths to date. It a novel strain from Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); 7th known member coronavirus family cause in humans, notably following Middle East syndrome (MERS), (SARS). The most characteristic feature this single-stranded RNA molecule includes spike glycoprotein on its surface. Most patients COVID-19, which elderly immunocompromised are at risk, complain flu-like symptoms, including dry cough headache. common complications include pneumonia, acute respiratory distress syndrome, septic shock, cardiovascular manifestations. Transmission SARS-CoV-2 mainly via droplets, either directly air when an infected patient coughs or sneezes, form fomites surfaces. Maintaining hand-hygiene, social distancing, personal protective equipment (i.e., masks) remain effective precautions. Patient management supportive care anticoagulative measures, focus maintaining function. Therapy dexamethasone, remdesivir, tocilizumab appear be promising date, hydroxychloroquine, lopinavir, ritonavir, interferons falling out favour. Additionally, accelerated vaccination efforts have taken place internationally, several vaccinations being mass deployed. In response COVID-19 pandemic, countries stakeholders varying precautions combat contain spread virus dampen collateral economic damage. This review paper aims synthesize impact global, micro macro scale.

Language: Английский

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Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Feb. 11, 2021

SUMMARY Background Tocilizumab is a monoclonal antibody that binds to the receptor for interleukin (IL)-6, reducing inflammation, and commonly used treat rheumatoid arthritis. We evaluated safety efficacy of tocilizumab in adult patients admitted hospital with COVID-19 evidence both hypoxia systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation Therapy [RECOVERY]), assessing several possible treatments hospitalised UK. Those participants (oxygen saturation <92% on air or requiring oxygen therapy) inflammation (C-reactive protein [CRP] ≥75 mg/L) were eligible randomisation usual standard care alone versus plus at dose 400 mg 800 (depending weight) given intravenously. A second could be 12 24 hours later if patient’s condition had not improved. The primary outcome was 28-day mortality, assessed intention-to-treat population. registered ISRCTN (50189673) clinicaltrials.gov ( NCT04381936 ). Findings Between 23 April 2020 January 2021, 4116 adults included assessment tocilizumab, including 562 (14%) receiving invasive mechanical ventilation, 1686 (41%) non-invasive respiratory support, 1868 (45%) no support other than oxygen. Median CRP 143 [IQR 107-204] mg/L 3385 (82%) corticosteroids randomisation. Overall, 596 (29%) 2022 allocated 694 (33%) 2094 died within 28 days (rate ratio 0·86; 95% confidence interval [CI] 0·77-0·96; p=0·007). Consistent results seen all pre-specified subgroups patients. In particular, clear mortality benefit those corticosteroids. Patients more likely discharged from alive (54% vs. 47%; rate 1·22; CI 1·12-1·34; p<0·0001). Among ventilation baseline, less reach composite endpoint death (33% 38%; risk 0·85; 0·78-0·93; p=0·0005). Interpretation improved survival clinical outcomes. These benefits regardless level additional Funding UK Research Innovation (Medical Council) National Institute Health (Grant ref: MC_PC_19056).

Language: Английский

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Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

Emerging Microbes & Infections, Journal Year: 2021, Volume and Issue: 10(1), P. 507 - 535

Published: Jan. 1, 2021

Without modern medical management and vaccines, the severity of Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) might approach magnitude 1894-plague (12 million deaths) 1918-A(H1N1) influenza (50 pandemics. The COVID-19 was heralded 2003 SARS epidemic which led to discovery human civet SARS-CoV-1, bat SARS-related-CoVs, Middle East (MERS)-related CoV HKU4 HKU5, other novel animal coronaviruses. suspected animal-to-human jumping 4 betacoronaviruses including coronaviruses OC43(1890), SARS-CoV-1(2003), MERS-CoV(2012), SARS-CoV-2(2019) indicates their significant potential. presence a large reservoir in bats wild mammals, culture mixing selling them urban markets with suboptimal hygiene, habit eating exotic mammals highly populated areas, rapid frequent air travels from these areas are perfect ingredients for brewing rapidly exploding epidemics. possibility emergence hypothetical SARS-CoV-3 or viruses animals laboratories, therefore needs global preparedness should not be ignored. We reviewed representative publications on epidemiology, virology, clinical manifestations, pathology, laboratory diagnostics, treatment, vaccination, infection control as 20 January 2021, is 1 year after person-to-person transmission SARS-CoV-2 announced. difficulties mass testing, labour-intensive contact tracing, importance compliance universal masking, low efficacy antiviral treatment disease, possibilities vaccine antiviral-resistant virus variants becoming another common cold discussed.

Language: Английский

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Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline

European Respiratory Journal, Journal Year: 2021, Volume and Issue: 57(4), P. 2100048 - 2100048

Published: March 10, 2021

Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising standardising management through evidence-based guidelines may improve quality care therefore patient outcomes.A task force from the European Respiratory Society endorsed by Chinese Thoracic identified priority interventions (pharmacological non-pharmacological) for initial version this "living guideline" using PICO (population, intervention, comparator, outcome) format. The GRADE approach was used assessing evidence strength recommendations. Systematic literature reviews were performed, data pooled meta-analysis where possible. Evidence tables presented to decision frameworks formulate recommendations.Based on available at time guideline development (20 February, 2021), panel makes strong recommendation in favour use systemic corticosteroids requiring supplementary oxygen ventilatory support, anticoagulation hospitalised patients. conditional interleukin (IL)-6 receptor antagonist monoclonal antibody treatment high-flow nasal continuous positive airway pressure hypoxaemic failure. make recommendations against hydroxychloroquine lopinavir-ritonavir. Conditional are made azithromycin, combined colchicine, remdesivir, latter case specifically mechanical No remdesivir supplemental oxygen. Further research made.The base COVID-19 now supports specific interventions. These will be regularly updated further becomes available.

Language: Английский

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