scholarly journals The Activin/FLRG pathway associates with poor COVID-19 outcomes in hospitalized patients

2021 ◽  
Author(s):  
Megan McAleavy ◽  
Qian Zhang ◽  
Peter J. Ehmann ◽  
Jianing Xu ◽  
Matthew F. Wipperman ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Viral Load ◽  
Hospital Admission ◽  
Activin A ◽  
Severe Form ◽  
Cytokine Storm ◽  
Acute Respiratory Disease ◽  
Hamster Model ◽  
All Cause Mortality ◽  
Nf Kappab

A subset of hospitalized COVID-19 patients, particularly the aged and those with co-morbidities, develop the most severe form of the disease, characterized by Acute Respiratory Disease Syndrome (ARDS), coincident with experiencing a “cytokine storm." Here, we demonstrate that cytokines which activate the NF-kappaB pathway can induce Activin A. Patients with elevated Activin A, Activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that Activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of Activin. To evaluate this, the role for Activin A was examined in a hamster model of SARS-CoV2 infection, via blockade of Activin A signaling. The hamster model demonstrated that use of an anti-ActivinA antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of Activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.

scholarly journals Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway

2021 ◽  
Author(s):  
Megan McAleavy ◽  
Qian Zhang ◽  
Jianing Xu ◽  
Li Pan ◽  
Matthew Wakai ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Activin A ◽  
Severe Form ◽  
Acute Respiratory Disease ◽  
Nf Kappa B ◽  
Sample Median ◽  
Longitudinal Outcomes ◽  
All Cause Mortality ◽  
Patients At Risk ◽  
Nf Kappab

SummaryA fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.

scholarly journals REGEN-COV for the Treatment of Hospitalized Patients with Covid-19

2021 ◽  
Author(s):  
Selin Somersan-Karakaya ◽  
Eleftherios Mylonakis ◽  
Vidya P. Menon ◽  
Jason C. Wells ◽  
Shazia Ali ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Viral Load ◽  
Supplemental Oxygen ◽  
Hospitalized Patients ◽  
Low Flow ◽  
Baseline Viral Load ◽  
Post Exposure Prophylaxis ◽  
Positive Trend ◽  
Risk Of Death ◽  
All Cause Mortality

Background: Hospitalized patients with Covid-19 experience high mortality rates, ranging from 10-30%. Casirivimab and imdevimab (REGEN-COV) is authorized in various jurisdictions for use in outpatients with Covid-19 and in post-exposure prophylaxis. The UK-based platform RECOVERY study reported improved survival in hospitalized seronegative patients treated with REGEN-COV, but in most of the world, anti-spike monoclonal antibody therapy is currently not approved for use in hospitalized patients. Methods: In this phase 1/2/3 double-blind placebo-controlled trial, patients on low-flow or no supplemental oxygen hospitalized with Covid-19 were randomized (1:1:1) to 2.4 g or 8.0 g REGEN-COV or placebo and characterized at baseline for viral load and SARS-CoV-2 endogenous immune response. Results: 1336 patients on low-flow or no supplemental oxygen were treated. The primary endpoint was met: in seronegative patients, the LS mean difference (REGEN-COV vs. placebo) for TWA change from baseline viral load was -0.28 log10 copies/mL (95% CI: -0.51, -0.05; P=0.0172). The primary clinical analysis of death or mechanical ventilation from day 6-29 in patients with high-viral load had a strong positive trend but did not reach significance. REGEN-COV reduced all-cause mortality in seronegative patients through day 29 (RRR, 55.6%; 95% CI: 24.2%, 74%). No safety concerns were noted overall nor in seropositive patients. Conclusions: In hospitalized patients with Covid-19 on low-flow or no oxygen, REGEN-COV treatment reduced viral load and the risk of death or mechanical ventilation as well as all-cause mortality in the overall population, with the benefit driven by seronegative patients and no harm observed in seropositive patients. (ClinicalTrials.gov number, NCT04426695.)

scholarly journals Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Eleni Papoutsi ◽  
Vassilis G. Giannakoulis ◽  
Eleni Xourgia ◽  
Christina Routsi ◽  
Anastasia Kotanidou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Meta Analysis ◽  
Mortality And Morbidity ◽  
Icu Admission ◽  
All Cause Mortality ◽  
Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

scholarly journals A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19

2021 ◽  
pp. 088506662199405
Author(s):  
Justine J. Ko ◽  
Clay Wu ◽  
Neha Mehta ◽  
Noah Wald-Dickler ◽  
Wei Yang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Intensive Care ◽  
Los Angeles ◽  
Usual Care ◽  
Low Income ◽  
Corticosteroid Treatment ◽  
Intensive Care Patients ◽  
Institutional Review ◽  
Mortality Effect ◽  
All Cause Mortality

Objectives: This study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring intensive care. Design: This is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit (ICU) admission. Patients admitted and requiring oxygen supplementation were treated with no steroids, methylprednisolone, or dexamethasone. Setting: This study takes place in the ICU’s at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles. Patients: All eligible patients admitted to the ICU for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study. Interventions: A total of 262 patients were grouped as receiving usual care (n = 75), methylprednisolone dosed at least at 1mg/kg/day for ≥ 3 days (n = 104), or dexamethasone dosed at least at 6 mg for ≥7 days (n = 83). Measurements and Main Results: All-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient. In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days ( P < 0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, P = 0.0385). Conclusions: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

scholarly journals C-Reactive Protein and All-Cause Mortality in a Large Hospital-Based Cohort

2008 ◽  
Vol 54 (2) ◽  
pp. 343-349 ◽  
Author(s):  
Claudia Marsik ◽  
Lili Kazemi-Shirazi ◽  
Thomas Schickbauer ◽  
Stefan Winkler ◽  
Christian Joukhadar ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Acute Phase ◽  
Cox Regression ◽  
Disease Risk ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Low Sensitivity

Abstract Background: C-reactive protein (CRP), an acute-phase protein, is a sensitive systemic marker of inflammation and acute-phase reactions. Testing CRP concentrations at hospital admission may provide information about disease risk and overall survival. Methods: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3–7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis. Results: Compared to individuals within the reference category (CRP &lt;5 mg/L), hazard ratios (HR) for all-cause mortality increased from 1.4 (5–10 mg/L category) to 3.3 in the highest category (&gt;80 mg/L, all P &lt;0.001). CRP was associated with various causes of death. The relation of CRP to cancer death was stronger than to vascular death. Younger patients with increased CRP had relatively far worse outcome than older patients (maximal HR: ≤30 years: 6.7 vs &gt;60 years: 1.7–3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (&gt;80 mg/L: HR 22.8 vs 1.4). Conclusion: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high CRP not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.

scholarly journals Tocilizumab in hospitalized patients with COVID-19: A meta analysis of randomized controlled trials

2021 ◽  
Author(s):  
Vijairam Selvaraj ◽  
Mohammad Saud Khan ◽  
Kwame Dapaah-Afriyie ◽  
Arkadiy Finn ◽  
Chirag Bavishi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Controlled Trials ◽  
Standard Therapy ◽  
Treatment Guidelines ◽  
Meta Analysis ◽  
Hospitalized Patients ◽  
Controlled Trials ◽  
Mortality And Morbidity ◽  
Randomized Controlled ◽  
All Cause Mortality

ABSTRACTBackgroundTo date, only dexamethasone has been shown to reduce mortality in COVID-19 patients. Tocilizumab has been recently added to the treatment guidelines for hospitalized COVID-19 patients, but data remains conflicting.MethodsElectronic databases such as MEDLINE, EMBASE and Cochrane central were searched from March 1, 2020, until February 28th, 2021, for randomized controlled trials evaluating the efficacy of tocilizumab in hospitalized COVID-19 patients. The outcomes assessed were all-cause mortality at 28 days, mechanical ventilation, and time to discharge.ResultsEight studies (with 6,311 patients) were included in the analysis. In total, 3,267 patients received tocilizumab, and 3,044 received standard care/placebo. Pooled analysis showed a significantly decreased risk of all-cause mortality at 28 days (RR 0.90, 95% CI 0.83-0.97, p=0.009) and progression to mechanical ventilation (RR 0.79, 95% CI 0.70-0.90, p=0.0002) in the tocilizumab arm compared to standard therapy or placebo. In addition, there was a trend towards improved median time to hospital discharge (RR 1.18, 95% CI 1.05-1.34, p=0.007).ConclusionsTocilizumab therapy improves outcomes of mortality and need for mechanical ventilation, in hospitalized patients with COVID-19 infection compared with standard therapy or placebo. Our findings suggest the efficacy of tocilizumab therapy in hospitalized COVID-19 patients and strengthen the concept that tocilizumab is a promising therapeutic intervention to improve mortality and morbidity in COVID-19 patients.

scholarly journals Misfortune never comes singly - the first case of COVID-19 with rupture of thoracic aortic aneurysm

2020 ◽  
Author(s):  
Kun Zhao ◽  
Zhang Cao ◽  
Changju Zhu ◽  
Yi Zhang ◽  
Feifan Chen
Keyword(s):  
Aortic Aneurysm ◽  
Severe Acute Respiratory Syndrome ◽  
Hospital Admission ◽  
Thoracic Aortic Aneurysm ◽  
Warning Signs ◽  
Cytokine Storm ◽  
Case Presentation ◽  
First Case

Abstract Background: SARS-CoV-2 is a newly discovered virus, leading COVID-19 a global threaten nowadays. Case Presentation: The first case of a patient with a thoracic aortic aneurysm (TAA) that became infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported here. The patient died suddenly from a ruptured aorta 19 h after hospital admission. Conclusion: COVID-19 patients with TAA should attract the highest vigilance as COVID-19 might expedite the process of TAA rupture through cytokine storm syndrome, leading to rapid death with little or no warning signs.

scholarly journals COVID-19 in pregnant women of Siberia and the Far East. Article

2020 ◽  
pp. 41-48
Author(s):  
N. V Artymuk ◽  
T. E Belokrinitskaya ◽  
O. S Filippov ◽  
E. M Shifman
Keyword(s):  
Mechanical Ventilation ◽  
Pregnant Women ◽  
Far East ◽  
Federal District ◽  
Severe Form ◽  
Comparative Assessment ◽  
Siberian Federal District ◽  
The Far East ◽  
Operational Information ◽  
Far Eastern

The purpose of the study was to conduct a comparative assessment of the incidence and characteristics of the course of the NCI COVID-19 in pregnant women in the Siberian Federal District and Far Eastern Federal District. Materials and methods. The analysis of operational information on the incidence of NCI COVID-19 and the features of the course in pregnant women, women in childbirth and puerperas provided by the chief obstetrician-gynecologists of the Siberian Federal District and the Far Eastern Federal District on May 25, 2020 is carried out. Results. The results of the study showed that the proportion of pregnant women among patients with COVID-19 in the Siberian Federal District and the Far Eastern Federal District is 0.82 %. Pneumonia was registered in almost every third patient (28.4 %), but the disease, on the whole, was characterized by a milder course than in the general population of patients: a severe form of the disease was diagnosed in 3.6 % of women, hospitalization in RAO was performed in 1.9 % of cases, mechanical ventilation was required by 0.6 % of patients. There were no cases of maternal and perinatal mortality. Conclusion. The course of the disease in pregnant women in the Siberian Federal District and the Far Eastern Federal District was characterized by a milder course relative to the general patient population. However, final conclusions can only be drawn after the pandemic is over. щей популяции больных. Однако окончательные выводы можно будет сделать только после завершения пандемии.

COVID-19 and hematologic diseases: Risk factors and long-term follow-up of CHRONOS19 Registry.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18715-e18715
Author(s):  
Kristina Zakurdaeva ◽  
Olga A. Gavrilina ◽  
Anastasia N. Vasileva ◽  
Sergei Dubov ◽  
Vitaly S. Dubov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Disease Progression ◽  
Primary Endpoint ◽  
Acute Leukemias ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Long Term Follow Up

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]

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