scholarly journals Impact of tocilizumab administration on mortality in severe COVID-19

2020 ◽  
Author(s):  
Andrew Tsai ◽  
Oumou Diawara ◽  
Ronald G Nahass ◽  
Luigi Brunetti
Keyword(s):  
Pulmonary Disease ◽  
Propensity Scores ◽  
Medical Center ◽  
Healthcare Providers ◽  
Severity Of Illness ◽  
Standard Of Care ◽  
Care Group ◽  
Chronic Pulmonary Disease ◽  
Cytokine Storm ◽  
Novel Coronavirus

Background The novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to a cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. Methods A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. Results A total of 132 patients were included in the matched dataset (tocilizumab=66; standard of care=66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the standard of care group (odds ratio, 1.0; 95% confidence interval, 0.465 - 2.151; p=1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died. Interpretation The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.

scholarly journals Impact of tocilizumab administration on mortality in severe COVID-19

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrew Tsai ◽  
Oumou Diawara ◽  
Ronald G. Nahass ◽  
Luigi Brunetti
Keyword(s):  
Pulmonary Disease ◽  
Propensity Scores ◽  
Medical Center ◽  
Healthcare Providers ◽  
Severity Of Illness ◽  
Chronic Pulmonary Disease ◽  
Cytokine Storm ◽  
Significant Burden ◽  
History Of ◽  
Novel Coronavirus

Abstract The novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to an aberrant inflammatory response or cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. A total of 274 patients meeting inclusion and exclusion criteria were identified and 132 patients were included in the matched dataset (tocilizumab = 66; no tocilizumab = 66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group (odds ratio, 1.0; 95% confidence interval, 0.465 – 2.151; p = 1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.

scholarly journals Early Tocilizumab Dosing is Associated with Improved Survival In Critically Ill Patients Infected With Sars-CoV-2

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nicholas W. Van Hise ◽  
Nathan C. Skorodin ◽  
Robert M. Fliegelman ◽  
Vishnu Chundi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Markers ◽  
Standard Of Care ◽  
Control Group ◽  
Cytokine Storm ◽  
Novel Coronavirus ◽  
Multi Center Study ◽  
Center Study

AbstractBackgroundSARS-CoV-2 is a novel coronavirus that has rapidly expanded to become a pandemic, resulting in millions of deaths worldwide. The cytokine storm is caused by the release of inflammatory agents and results in a physiologic disruption. Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsThis was a multi-center study of patients infected with SARS-CoV-2, admitted between 3/13/20 and 4/16/20, requiring mechanical ventilation. Parameters that were evaluated included age, sex, race, usage of steroids, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was utilized for comparison (untreated).FindingsWe studied 118 patients who required mechanical ventilation. Eighty-one (81) received tocilizumab, compared to 37 who were untreated. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p=0.003). Dosing tocilizumab late was associated with an increased mortality compared to the untreated group (p=0.006).InterpretationEarly tocilizumab administration was associated with decreased mortality in critically ill SARS-Co-V-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.FundingThis work did not receive outside funding or sponsorship.

scholarly journals Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care

2020 ◽  
Author(s):  
Luca Quartuccio ◽  
Arianna Sonaglia ◽  
Dennis McGonagle ◽  
Martina Fabris ◽  
Maddalena Peghin ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Conflicts Of Interest ◽  
Standard Of Care ◽  
Good Prognosis ◽  
Care Group ◽  
List Type ◽  
Cytokine Storm ◽  
Prognostic Features ◽  
The Impact ◽  
Bacterial Superinfection

AbstractObjectiveApproximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or “cytokine storm”. Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point.MethodsBetween February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC).ResultsIn the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8±10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients.ConclusionHigher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.FundingThis research received no external funding.Conflicts of Interest“The authors declare no conflict of interest.”HighlightsThere is an urgent need for markers of prognosis in COVID-19.Higher inflammatory markers best select tocilizumab treatment.The ward based tocilizumab group showed better responses and less infections than ICU tocilizumab group.The former group may be the best for evaluating the impact of anti-cytokine therapy in COVID-19.The known poor risk factors for COVID-19 infection were present in the TOCI treated rather than in the good prognosis standard of care group.

Patient isolation for infection control and patient experience

2018 ◽  
Vol 40 (2) ◽  
pp. 194-199
Author(s):  
Zishan K. Siddiqui ◽  
Sarah Johnson Conway ◽  
Mohammed Abusamaan ◽  
Amanda Bertram ◽  
Stephen A. Berry ◽  
...  
Keyword(s):  
Patient Experience ◽  
Dose Response ◽  
Medical Center ◽  
Academic Medical Center ◽  
Tertiary Care ◽  
Healthcare Providers ◽  
Severity Of Illness ◽  
Carrier State ◽  
Response Effect ◽  
Dose Response Effect

AbstractObjectiveHospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication.DesignRetrospective analysis of HCAHPS survey results over 5 years.SettingA 1,165-bed, tertiary-care, academic medical center.PatientsPatients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls.MethodsMultivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and “top-box” experience scores. Dose response to increasing percentage of days in isolation was also analyzed.ResultsPatients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed.ConclusionIsolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.

Abstract 111: Outcomes for Patients Receiving Cardiopulmonary Resuscitation During Novel Coronavirus Outbreak in The United States

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Priyanka Sheth ◽  
Habeeb F Kazimuddin ◽  
Douglas McElroy ◽  
Aniruddha Singh
Keyword(s):  
Patient Outcomes ◽  
Medical Center ◽  
Healthcare Providers ◽  
Patient Characteristics ◽  
The United States ◽  
Spontaneous Circulation ◽  
Healthcare Personnel ◽  
Chi Square ◽  
Significant Difference ◽  
Novel Coronavirus

Introduction: Since the start of the novel coronavirus outbreak in the U.S., the CDC and AHA have introduced new CPR guidelines involving increased precautions for protecting healthcare providers from infection. These precautions have been widely adopted for both known and potential COVID+ patients despite debate over increased strain on CPR providers and potentially inferior outcomes. In order to bridge the knowledge gap surrounding safe, effective CPR practices in the presence of COVID-19, patient outcomes for codes performed in our medical center since March 2020 were compared to those of the same time last year. Methods: A total of 94 hospital codes across 80 patients were included. Age, BMI, and code duration were tested for significant differences in means between groups using ANOVA, with pairwise comparisons done using Tukey’s HSD test. Discrete variables were tested for significant differences among groups using chi-square association tests. Results: Groups were well matched on patient characteristics. There were no significant differences in age, comorbidities, or rhythm type among groups. COVID+ patients had significantly higher BMI than non-COVID patients. Code duration was significantly greater in the COVID+ group. However, there was no significant difference in code survival; 5 of 10 COVID+ patients (50%) survived the code event, compared to 54 of 84 (64%) non-COVID patients. Only 1 of 10 (10%) COVID+ patients was discharged alive vs. 18 of 71 non-COVID patients (25%); while not significant, this difference is perhaps worthy of further attention. Conclusions: Patient outcomes between 2019 and 2020 were comparable, indicating that extra precautions taken by healthcare personnel during the COVID-19 outbreak are not degrading the quality of CPR administered. However, COVID+ patients had significantly longer code durations than non-COVID patients in both years, suggesting a greater difficulty in restoring spontaneous circulation in the virus group.

scholarly journals Dual-Histamine Blockade with Cetirizine - Famotidine Reduces Pulmonary Symptoms in COVID-19 Patients

2020 ◽  
Author(s):  
Reed B. Hogan ◽  
Reed B. Hogan ◽  
Tim Cannon ◽  
Maria Rappai ◽  
John Studdard ◽  
...  
Keyword(s):  
Cohort Study ◽  
Medical Center ◽  
Standard Of Care ◽  
Cytokine Storm ◽  
Do Not Resuscitate ◽  
Combination Drug ◽  
Inpatient Outcomes ◽  
High Acuity ◽  
Duration Of Hospitalization ◽  
Concomitant Medications

AbstractBackgroundThe COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 blockers improve COVID-19 inpatient outcomes?MethodsA physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg and famotidine 20 mg b.i.d. plus standard-of-care.ResultsOf all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine blockade for at least 48 hours, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 hours of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited reductions in symptom progression when compared to published reports of COVID-19 patients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes.ConclusionsThis physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a new safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine blockers.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals AEROBIC EXERCISE VOLUME, NOT PRESCRIPTION, INFLUENCES POST-CONCUSSION SYMPTOMS: A RANDOMIZED CLINICAL TRIAL

2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0014
Author(s):  
David R. Howell ◽  
Danielle Hunt ◽  
Stacey E. Aaron ◽  
William P. Meehan ◽  
Can Ozan Tan
Keyword(s):  
Clinical Trial ◽  
Aerobic Exercise ◽  
Symptom Severity ◽  
Exercise Prescription ◽  
Standard Of Care ◽  
Care Group ◽  
Initial Symptom ◽  
Initial Visit ◽  
Severity Scores ◽  
Text Figure

Background: Current recommendations for sport-related concussion uniformly emphasize the importance of physical activity. However, specifics of this recommendation remain vague and do not account for an exercise dosage or compliance. Purposes: First, we examined if an 8-week individualized sub-symptom threshold aerobic exercise prescription, initiated within the first two weeks of concussion, alleviates symptom severity or affects the amount of exercise performed during the study. Second, we examined whether prescription adherence, rather than randomized group assignment, reflects the actual impact of aerobic exercise in post-concussion recovery. Methods: For this single-site prospective randomized clinical trial, participants completed an aerobic exercise test within 14 days of injury, and were randomized to an individualized aerobic exercise program or standard-of-care, and returned for assessments 1 month and 2 months after the initial visit (Table 1). The aerobic exercise group was instructed to exercise 5 days/week, 20 minutes/day, at a target heart rate based on an exercise test at the initial visit. Participants reported their symptom exercise volume each week over the 8-week study period, and reported symptoms at each study visit (initial, 1 month, 2 month). Results: Initial symptom severity was not different between randomized groups (Figure 1A), and no significant differences in symptom severity were found at the 4-week (Figure 1B) or 8-week (Figure 1C) assessment. In addition, there was no significant differences between groups for average weekly exercise volume during the first four weeks (Figure 2A) or second four weeks (Figure 2B) of the study. During the first four weeks of the study, 65% (n=11/17) of the exercise intervention participants were compliant with their exercise recommendation (≥100 min/week), compared to 45% (n=9/20) of the standard-of-care group (p=0.33). During the second four weeks of the study, 71% (n=12/17) of the exercise prescription group exercised ≥100 min/week, compared to 55% (n=11/20) of the standard-of-care group (p=0.50). When grouped by exercise volume, the group who exercised ≥100 minutes/week during the first month of the study reported significantly lower symptom severity scores than those who exercised <100 minutes/week (Figure 3B), despite similar initial symptom severity scores (Figure 3A). Conclusion: Participant randomization within 14 days of concussion did not lead to a significant reduction in symptoms, or greater exercise volume. Given that greater exercise volume was associated with lower symptoms after one month of the study, researchers and clinicians should pay particular attention to adherence to aerobic exercise programs for the treatment of concussion. [Table: see text][Figure: see text][Figure: see text][Figure: see text]

scholarly journals Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms

2021 ◽  
Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  
Keyword(s):  
Decision Making ◽  
Male Patient ◽  
Young Male ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Invasive Ventilation ◽  
Organ Systems ◽  
The Central Nervous System

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.

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