A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19 DOI
Michael E. Bowdish, Christina E. Barkauskas, Jessica Overbey

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2022, Volume and Issue: 207(3), P. 261 - 270

Published: Sept. 13, 2022

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety allogeneic mesenchymal in mechanically-ventilated moderate or severe COVID-19-induced failure. Methods: Patients were randomized to two infusions 2 million cells/kg sham infusions, addition the standard care. We hypothesized that cell therapy would be superior control primary endpoint 30-day mortality. The key secondary was ventilator-free survival within 60 days, accounting deaths withdrawals a ranked analysis. Measurements Main Results: At third interim analysis, data monitoring board recommended trial halt enrollment prespecified mortality reduction from 40% 23% unlikely achieved (n = 222 out planned 300). Thirty-day 37.5% (42/112) recipients versus 42.7% (47/110) (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P 0.43). no significant differences days alive off ventilation (median rank, 117.3 [interquartile range, 60.0-169.5] 102.0 54.0-162.5] subjects; higher is better). Resolution improvement at 30 observed 51/104 (49.0%) 46/106 (43.4%) (odds ratio, 1.36; 0.57-3.21). infusion-related toxicities overall serious adverse events over similar. Conclusions: cells, while safe, did not improve 60-day and/or COVID-19-related syndrome.

Language: Английский

SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis DOI Creative Commons
Daniel Wendisch, Oliver Dietrich, Tommaso Mari

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(26), P. 6243 - 6261.e27

Published: Nov. 27, 2021

Language: Английский

Citations

423
The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19 DOI
Christoph Schultheiß, Edith Willscher, Lisa Paschold

et al.

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(6), P. 100663 - 100663

Published: June 1, 2022

Language: Английский

Citations

317
Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19 DOI Open Access
Gavin D. Perkins, Chen Ji, Bronwen Connolly

et al.

JAMA, Journal Year: 2022, Volume and Issue: 327(6), P. 546 - 546

Published: Jan. 24, 2022

Importance

Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness safety of these noninvasive strategies.

Objective

To determine whether either CPAP or HFNO, compared conventional therapy, improves clinical outcomes hospitalized COVID-19–related failure.

Design, Setting, Participants

A parallel group, adaptive, randomized trial 1273 adults The was conducted between April 6, 2020, May 3, 2021, across 48 care hospitals UK Jersey. Final follow-up occurred on June 20, 2021.

Interventions

Adult were to receive (n = 380), HFNO 418), therapy 475).

Main Outcomes Measures

primary outcome a composite tracheal intubation mortality within 30 days.

Results

stopped prematurely due declining COVID-19 case numbers end funded recruitment period. Of (mean age, 57.4 [95% CI, 56.7 58.1] years; 66% male; 65% White race), data available 1260. Crossover interventions 17.1% participants (15.3% 11.5% 23.6% group). requirement days significantly lower (36.3%; 137 377 participants) vs (44.4%; 158 356 (absolute difference, −8% −15% −1%],P .03), but not different (44.3%; 184 415 (45.1%; 166 368 −1% 6%],P .83). Adverse events 34.2% (130/380) 20.6% (86/418) 13.9% (66/475) group.

Conclusions Relevance

Among COVID-19, an initial strategy reduced risk there no significant difference therapy. study may underpowered comparison early termination crossover among groups should be considered when interpreting findings.

Trial Registration

isrctn.org Identifier:ISRCTN16912075

Language: Английский

Citations

306
Monocytes and Macrophages in COVID-19 DOI Creative Commons
Rainer Knoll, Joachim L. Schultze, Jonas Schulte-Schrepping

et al.

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

Published: July 21, 2021

COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The characterized primarily, but not exclusively, respiratory clinical manifestations ranging from mild common cold symptoms, including cough fever, severe distress multi-organ failure. Macrophages, heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes complex ontogeny present in all mammalian organs, play critical roles developmental, homeostatic host defense processes tissue-dependent plasticity. In case infection, they are responsible for early pathogen recognition, initiation resolution inflammation, as well repair tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, recruited under pathological conditions such infections the affected defend organism against invading pathogens aid efficient inflammation. Given their pivotal function potential danger posed dysregulated hyperinflammation, understanding monocyte macrophage phenotypes key tackling disease's mechanisms. Here, we outline current knowledge on monocytes macrophages homeostasis summarize concepts findings role COVID-19. While blood patients moderate inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized loss HLA-DR expression induction S100 alarmin dominant feature disease. Pulmonary infiltrating inflammatory hyperactivated state resulting detrimental loop pro-inflammatory cytokine release recruitment cytotoxic effector cells thereby exacerbating damage at site infection.

Language: Английский

Citations

237
Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study DOI Creative Commons
S. Charfeddine, Hassen Ibn Hadj Amor, Jihen Jdidi

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Nov. 30, 2021

The COVID-19 disease is a multisystem due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after infection may be persistent endothelial dysfunction. Our study focused on evaluation of quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath large cohort long patients determine whether long-covid 19 symptoms are associated This cross-sectional multicenter observational prospective recruitment patients. A total 798 were included this study. 618 (77.4%) had symptoms. mean EQI was 2.02 ± 0.99 IC95% [1.95-2.08]. 397 (49.7%) impaired EQI. Fatigue, chest pain, neuro-cognitive difficulties significantly dysfunction an <2 adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, severity acute infection. In multivariate analysis, (EQI <2), female gender, severe clinical status at need oxygen supplementation independent risk factors syndrome. Long symptoms, specifically non-respiratory These findings allow better care

Language: Английский

Citations

175
Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations DOI Creative Commons
Matteo Parotto, Mariann Gyöngyösi, Kathryn L. Howe

et al.

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(8), P. 739 - 754

Published: July 17, 2023

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after phase, lasting for weeks months initial illness. The post-acute sequelae COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID post-COVID-19 condition. substantial burden this multisystem condition is felt at individual, health-care system, socioeconomic levels, on an unprecedented scale. Survivors COVID-19-related critical illness risk respiratory distress syndrome, sepsis, chronic illness, these multidimensional morbidities might be difficult to differentiate from specific effects COVID-19. We provide overview manifestations in adults. explore various organ systems, describe potential pathophysiological mechanisms, consider challenges providing clinical care support survivors manifestations. Research needed reduce incidence optimise therapeutic rehabilitative patients.

Language: Английский

Citations

137
The human genetic epidemiology of COVID-19 DOI Open Access
Mari Niemi, Mark J. Daly, Andrea Ganna

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 533 - 546

Published: May 2, 2022

Language: Английский

Citations

119
Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19 DOI
Fotios Karagiannis, Konrad Peukert, Laura Surace

et al.

Nature, Journal Year: 2022, Volume and Issue: 609(7928), P. 801 - 807

Published: July 28, 2022

Language: Английский

Citations

114
Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials DOI Open Access
Alain Amstutz, Benjamin Speich, France Mentré

et al.

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(5), P. 453 - 464

Published: Feb. 22, 2023

Language: Английский

Citations

92
Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection DOI Creative Commons
Stephanie A Richard, Simon Pollett, Anthony C Fries

et al.

JAMA Network Open, Journal Year: 2023, Volume and Issue: 6(1), P. e2251360 - e2251360

Published: Jan. 18, 2023

Importance Understanding the factors associated with post-COVID conditions is important for prevention. Objective To identify characteristics persistent post–COVID-19 symptoms and to describe medical encounters. Design, Setting, Participants This cohort study used data from Epidemiology, Immunology, Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) implemented in US military health system (MHS); MHS beneficiaries aged 18 years or older who tested positive SARS-CoV-2 February 28, 2020, through December 31, 2021, were analyzed, 1-year follow-up. Exposures infection. Main Outcomes Measures The outcomes analyzed included survey-reported 6 months after infection International Statistical Classification Related Health Problems, Tenth Revision diagnosis categories reported records following vs 3 before Results More than half 1832 participants these analyses 44 (1226 [66.9%]; mean [SD] age, 40.5 [13.7] years), male (1118 [61.0%]), unvaccinated at time their (1413 [77.1%]), had no comorbidities (1290 [70.4%]). A total 728 (39.7%) illness that lasted 28 days longer (28-89 days: 364 [19.9%]; ≥90 [19.9%]). prior (risk ratio [RR], 1.39; 95% CI, 1.04-1.85), moderate (RR, 1.80; 1.47-2.22) severe 2.25; 1.80-2.81) initial illnesses, more hospitalized (RR per each day hospitalization, 1.02; 1.00-1.03), a Charlson Comorbidity Index score 5 greater 1.55; 1.01-2.37) likely report symptoms. Among participants, postinfection vaccination was 41% lower risk reporting 0.59; 0.40-0.89). higher pulmonary 2.00; 1.40-2.84), diabetes 1.46; 1.00-2.13), neurological 1.29; 1.02-1.64), mental health–related encounters 1.28; 1.01-1.62) symptom onset baseline (before infection). Conclusions Relevance In this study, acute illness, score, being COVID-19 lasting more. seek care diabetes, pulmonary, neurological, least compared pre-COVID use patterns. These findings may inform risk-benefit policy.

Language: Английский

Citations

65