Bleeding disorders associated with severity of respiratory failure in covid-19 patients: A prospective observational study

INTRODUCTION: Despite the progress in understanding the pathophysiology of coagulopathy in COVID-19, data about the association and phasing of pathological changes in various parts of the hemostatic system with the development of acute respiratory distress syndrome (ARDS) are insufficient. OBJECTIVE: To determine association between the severity of respiratory failure and pathological changes in the hemostatic system in COVID-19 patients. MATERIALS AND METHODS: A prospective observational study included 204 patients with a confirmed diagnosis of severe and extremely severe COVID-19. Two groups were identified according to disease outcome: Fatal (n = 106) and survived (n = 98) groups. To assess dynamics of the clinical picture of the disease and to study the hemostatic profile, time points were determined: I point — the first day — admission to intensive care unit;II point — 3-5 days, III point — 7-10 days after ICU admission. The respiratory index was calculated to assess the severity of respiratory distress syndrome. Statistical data processing was carried out using the statistical software package MedCalc Version 20.110 (MedCalc Software Ltd, Belgium). RESULTS: A 2.15-fold decrease in the respiratory index was determined for fatal outcome in patients with severe and extremely severe COVID-19. The most important hemostatic parameters affecting the severity of respiratory failure are increased Willebrand factor concentration at I point of the study (21% contribution and inverse correlation), increased plasminogen activator inhibitor type 1 (PAI-1) level on 3-5 days (35% contribution and direct correlation), and activation of the coagulative component of hemostasis on 7-10 days (78% contribution and direct correlation). CONCLUSIONS: The severity of respiratory failure in patients with a confirmed diagnosis of severe and extremely severe COVID-19 is gradually associated with endotheliopathy (1 day), inhibition of parietal fibrinolysis (3-5 days) and activation of the coagulative component of hemostasis by 7-10 days of ICU stay. © 2023, Practical Medicine Publishing House LLC. All rights reserved.

Emergency Tracheostomy Due to a Myasthenic Crisis in a Post-COVID Patient: Report of a Case.

Myasthenia gravis is an autoimmune disorder caused by the production of antibodies that block either acetylcholine receptors or structural receptors of the neuromuscular junction. There is expanding evidence that novel coronavirus (2019-nCoV) disease can lead to the development of an autoimmune response. Myasthenic crisis, a life-threatening respiratory muscle weakness severe enough to necessitate intubation or tracheostomy, can be a potential complication of myasthenia gravis. In this report, we describe the case of a 57-year-old man with acute respiratory insufficiency requiring emergency tracheostomy. His health condition rapidly deteriorated 1 week after initiating systemic corticosteroid treatment for a suspected adult-onset asthma exacerbation. The patient had a history of COVID-19 infection and thymectomy, which were noted in his medical records. Serological testing and electrodiagnostic evaluation confirmed the diagnosis of myasthenia gravis. The patient was treated with plasma exchange, continuous neostigmine infusion, and prednisone. He was successfully decannulated and discharged with anticholinesterase inhibitors and long-term immunosuppression therapy. It is important to consider neurological disorders in the differential diagnosis for patients presenting with respiratory insufficiency, particularly during the COVID-19 pandemic.

Predictors of ICU Admission in Children with COVID-19: Analysis of a Large Mexican Population Dataset.

Children, although mostly affected mildly or asymptomatically, have also developed severe coronavirus disease 2019 (COVID-19). This study aims to assess potential predictors of intensive care unit (ICU) admission in a large population (n = 21,121) of children aged 0-9 years with laboratory-confirmed disease. We performed a cross-sectional analysis of a publicly available dataset derived from the normative epidemiological surveillance of COVID-19 in Mexico. The primary binary outcome of interest was admission to the ICU due to respiratory failure. Results showed that immunosuppressed children and those with a personal history of cardiovascular disease had a higher likelihood of being admitted to the ICU, while increasing age and the pandemic duration were associated with a lower likelihood of admission. The study's results have the potential to inform clinical decision-making and enhance management and outcomes for children affected by COVID-19 in Mexico.

Helmet Continuous Positive Airway Pressure in the Emergency Department: A Practical Guide.

Helmet continuous positive airway pressure is a simple, noninvasive respiratory support strategy to treat several forms of acute respiratory failure, such as cardiogenic pulmonary edema and pneumonia. Recently, it has been largely used worldwide during the COVID-19 pandemic. Given the increased use of helmet continuous positive airway pressure in the emergency department, we aimed to provide an updated practical guide for nurses and clinicians based on the latest available evidence. We focus our attention on how to set the respiratory circuit. Moreover, we discuss the interactions between flow generators, filters, and positive end-expiratory pressure valves and the consequences regarding the delivered gas flow, fraction of inspired oxygen, positive end-expiratory pressure, and noise level.

Pulmonary parenchymal involvement secondary to subcutaneous injection of silicone gels: a case report.

Pulmonary parenchymal involvement secondary to the subcutaneous injection of silicone gels is an unusual condition which occurs more frequently in women aged between 22 and 55 years. Although different theories have been put forward about its etiology, it is unknown and the condition may cause local and systemic complications and even have a fatal outcome. Few cases have been reported in South America and there is no report of this unique entity in Peru. We present the case of a previously healthy 28-year-old male transgender patient who, after an illegal subcutaneous injection of silicone gels in the gluteal region given by a non-healthcare professional, showed progressive respiratory distress and stabbing chest pain of approximately 7 out of 10 on the pain scale within the first 24 hours. Upon admission to the emergency room, respiratory failure was objectively evidenced since the patient had an oxygen saturation of 72 % at a FiO2 of 21 %, as well as pulmonary parenchymal involvement both in the CT scan and chest X-ray with signs highly suggestive of this pathology. Using a SARS-CoV-2 RNA real-time RT-PCR test performed on a respiratory specimen, COVID pneumonia, immunodeficiency disorders and pulmonary embolism were ruled out. Since there is no standard treatment, the patient was given relevant support measures such as the administration of supplemental oxygen at a low flow rate by binasal cannula, intravenous systemic corticosteroids and antibiotic therapy, thus achieving good progress with resolution of the initial clinical presentation. Then, after 10 days of intrahospital treatment, the patient was discharged.Copyright © La revista. Publicado por la Universidad de San Martin de Porres, Peru.

Factors associated with non-invasive positive pressure ventilation failure in a COVID-19 intermediate care unit.

BACKGROUND: The use of non-invasive positive pressure ventilation (NIPPV) in COVID-19 patients with hypoxaemia is still under debate. The aim was to evaluate the efficacy of NIPPV (CPAP, HELMET-CPAP or NIV) in COVID-19 patients treated in the dedicated COVID-19 Intermediate Care Unit of Coimbra Hospital and University Centre, Portugal, and to assess factors associated with NIPPV failure. METHODS: Patients admitted from December 1st 2020 to February 28th 2021, treated with NIPPV due to COVID-19 were included. Failure was defined as orotracheal intubation (OTI) or death during hospital stay. Factors associated with NIPPV failure were included in a univariate binary logistic regression analysis; those with a significance level of p < 0.001 entered a multivariate logistic regression model. RESULTS: A total of 163 patients were included, 64.4% were males (n = 105). The median age was 66 years (IQR 56-75). NIPPV failure was observed in 66 (40.5%) patients, 26 (39.4%) were intubated and 40 (60.6%) died during their hospital stay. The highest CRP (OR 1.164; 95%CI 1.036-1.308) and morphine use (OR 24.771; 95%CI 1.809-339.241) were identified as predictors of failure after applying multivariate logistic regression. Adherence to prone positioning (OR 0.109; 95%CI 0.017-0.700) and a higher value of the lowest platelet count during hospital stay (OR 0.977; 95%CI 0.960-0.994) were associated with a favorable outcome. CONCLUSIONS: NIPPV was successful in over half of patients. Highest CRP during hospital stay and morphine use were predictors of failure. Adherence to prone positioning and a higher value of the lowest platelet count during hospital stay were associated with a favourable outcome.

Association of complement pathways with COVID-19 severity and outcomes.

OBJECTIVES: Complement activation has been implicated in COVID-19 pathogenesis. This study aimed to assess the levels of complement activation products and full-length proteins in hospitalized patients with COVID-19, and evaluated whether complement pathway markers are associated with outcomes. METHODS: Longitudinal measurements of complement biomarkers from 89 hospitalized adult patients, grouped by baseline disease severity, enrolled in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial and treated with intravenous sarilumab (200 mg or 400 mg) or placebo (NCT04315298), were performed. These measurements were then correlated with clinical and laboratory parameters. RESULTS: All complement pathways were activated in hospitalized patients with COVID-19. Alternative pathway activation was predominant earlier in the disease course. Complement biomarkers correlated with multiple variables of multi-organ dysfunction and inflammatory injury. High plasma sC5b-9, C3a, factor Bb levels, and low mannan-binding lectin levels were associated with increased mortality. Sarilumab treatment showed a modest inhibitory effect on complement activation. Moreover, sera from patients spontaneously deposited C5b-9 complex on the endothelial surface ex vivo, suggesting a microvascular thrombotic potential. CONCLUSION: These results advance our understanding of COVID-19 disease pathophysiology and demonstrate the importance of specific complement pathway components as prognostic biomarkers in COVID-19.

A new logistic regression derived combined index for early prediction of in-hospital mortality in COVID-19 patients

BACKGROUND: While the type and the number of treatments for Coronavirus Disease 2019 (COVID-19) have substantially evolved since the start of the pandemic a significant number of hospitalized patients continue to succumb. This requires ongoing research in the development and improvement of early risk stratification tools. METHOD(S): We developed a prognostic score using epidemiological, clinical, laboratory, and treatment variables collected on admission in 130 adult COVID-19 patients followed until in-hospital death (N.=38) or discharge (N.=92). Potential variables were selected via multivariable logistic regression modelling conducted using a logistic regression univariate analysis to create a combined index. RESULT(S): Age, Charlson Comorbidity Index, P/F ratio, prothrombin time, C-reactive protein and troponin were the selected variables. AUROC indicated that the model had an excellent AUC value (0.971, 95% CI 0.926 to 0.993) with 100% sensitivity and 83% specificity for in-hospital mortality. The Hosmer-Lemeshow calibration test yielded non-significant P values (chi2=1.79, P=0.99) indicates good calibration. CONCLUSION(S): This newly developed combined index could be useful to predict mortality of hospitalized COVID-19 patients on admission.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Survey of Home Cleaning Practices With Noninvasive Ventilation Equipment

Purpose:Home noninvasive ventilation (NIV) equipment is often observed to be dirty, potentially increasing patients' risk of respiratory infection. This study aimed to describe the cleaning practices of home NIV patients. Method(s):This single-site, cross-sectional, observational study surveyed 100 patients from the respiratory failure clinic regarding cleaning instructions, cleaning habits, barriers, and motivators to cleaning. Open-ended responses were analyzed with basic content analysis and closed categorical responses with frequencies and percentages. Result(s):Of 100 participants, 77% responded. Cleaning instructions most commonly recalled included cleaning with soapy water for masks (26/47, 55%), head straps (19/47, 40%), and tubing (21/47, 45%);vinegar solution for humidifiers (9/39, 23%);and replacing filters (14/39, 36%). Fourteen respondents reported barriers to cleaning, including forgetfulness (7/14, 50%) and physical difficulties (6/14, 43%). Commonly reported cleaning practices included soapy water to soak masks (28/77, 36%) and tubing (35/77, 46%), weekly masks (34/77, 44%) and tubing cleaning (29/77, 38%), vinegar solution to clean humidifiers for the 36 humidifier users (15/36, 44%), monthly humidifier cleaning (13/36, 36%), and monthly filter cleaning/replacement (36/77, 47%). Conclusion(s):Few respondents could recall specific instructions about when and how to clean their equipment. Many reported routine cleaning, with varied methods and frequencies. Our results will inform future NIV equipment cleaning educational package design.Copyright © Cardiovascular and Pulmonary Section, APTA.

COVID-19: Recent Advances in Lung Ultrasound

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV 2) has become a global threat that has led to tremendous societal instability. The SARS-CoV-2 can exhibit a drastic variation in terms of the signs and symptoms in the patient's body. This virus manifests its existence through cough, fever, sore throat, body aches, chest pain, headaches, and dyspnoea. These can lead to life-threatening respiratory insufficiency, thereby affecting several other organs such as the kid-ney, heart, lungs, liver, and nervous system. The lungs are the primary target site for SARS-CoV-2 and several diagnoses are being deployed in real time for treatment purposes. Although chest CT is the standard method for early diagnosis and management of Coronavirus Disease (COVID-19), lung ultrasound (US) has some merits over chest CT and may be used in addition to it in the workup of COVID-19. The goal of our review is to look at the observations of the reports on lung ultrasound in COVID-19 patients and the current advances.Copyright © 2023 Bentham Science Publishers.

Intermediate Respiratory Care Units: Questions and Answers

The intermediate respiratory care units (UCRI) are areas of monitoring and specialized care of patients with acute or chronic-exacerbated respiratory failure, whose severity does not require admission to an intensive care unit, but which due to their complexity cannot be treated in conventional hospitalization. Although the COVID-19 pandemic has proven its usefulness in the management of critical respiratory patients, the historical trajectory of the UCRI comes from many years ago, in which its cost-effectiveness has been demonstrated by far. This document presents a series of questions and answers on the history of the UCRI, in addition to the criteria for admission, infrastructure, human and technical resources, and the types of existing Units. Within the UCRI year 2021-2022 designated by the Spanish Society of Pneumology and Thoracic Surgery, any scientific dissemination linked to the in-depth knowledge of these units is timely, where multidisciplinarity and the work of professionals related to the care of critical respiratory patients converge.Copyright © 2022

Design and construction of automated mechanical ventilation equipment

This document presents the requirements met for the design, construction and initial validation of a mechanical ventilation system to be used in patients with respiratory insufficiency, which in the initial context was due to the COVID-19 pandemics. The design required the use of computer aided drawing software (Computer Aided Design) CAD and the construction required the use of installed capabilities in mechanical, electropneumatic, electronic, biomedical and automation manufacturing of institutes and centers of the Universidad Don Bosco (El Salvador). The adjust-ment, configuration and programming tasks were in charge of research professors specialized in these dis-ciplines. The elements used for its construction were available in the Salvadoran market, considering the closure of borders as a government measure to face the expansion of the pandemics. After the design, manufacturing and commissioning stage, conditions of the supplied air were measured with the help of professionals dedicated to the maintenance of medical equipment and with the approval of internist doctors. The results achieved are those obtained with paramedical equipment and with first aid equipment, and consequently it has been foreseen that the equipment can be tested in a subsequent instance with the certified medical union. © 2022, Universidad Politecnica Salesiana. All rights reserved.

The physiopathology of COVID acute respiratory failure

The current COVID-19 pandemic has posed an unusual challenge to health services in all countries. Although physiopathological knowledge about other coronaviruses, mainly SARS-CoV-1 and MERS, has been useful, SARS-CoV-2 has very particular aspects. Its lethality is lower than the previous ones, but its infectivity is much higher, which has resulted in a global expansion, not reached by previous viruses. The physiopathology of acute respiratory failure, in COVID-19, is especially complex and must be understood under a triple prism: specific viral action, the immunopathological response (which in turn has several phases) and the microvascular response. The fact that the elderly are particularly fragile to this virus is a particular challenge. Firstly, to understand what the differential physiopathological facts are. Secondly, to transfer this knowledge to the diagnostic and therapeutic field, in an attempt to reduce morbidity and mortality in this age group. At present, we need to continue to deepen our knowledge of the physiopathology of respiratory failure in the elderly in order to achieve the final objective in therapeutic terms. © Springer Nature Switzerland AG 2020.

Introducing helmet non-invasive ventilation during COVID-19 pandemic: Early experience of two centres.

Purpose: The helmet is a novel interface for delivering non-invasive ventilation (NIV). We conducted a case series to characterize introduction of the helmet interface in both COVID and non-COVID patients at two-centres. Methods: We enrolled all patients with respiratory failure admitted to the Juravinski Hospital (Hamilton, Canada) and St. Joseph's Health Center (Syracuse, New York) between November 1, 2020 and June 30, 2021 who used the helmet interface (Intersurgical StarMed) as part of this introduction into clinical practice. We collected patient demographics, reason for respiratory failure, NIV settings, device-related complications and outcomes. We report respiratory therapist's initial experiences with the helmet using descriptive results. Results: We included 16 patients with a mean age of 64.3 ± 10.9 years. The most common etiology for respiratory failure was pneumonia (81.3%). The median duration of NIV during the ICU admission was 67.5 (15.3, 80.8) hours, with a mean maximum PS of 13.9 ± 6.6 cm H2O and a mean maximum PEEP of 10.4 ± 5.1 cm H20. Three patients (18.7%) did not tolerate the helmet. Ten (62.5%) patients ultimately required intubation, and 7 (43.4%) patients died while in the ICU. The most common reason for intubation was worsening hypoxia (70%). No adverse events related to the helmet were recorded. Conclusion: Over the 8-month period of this study, we found that the helmet was well tolerated in over 80% of patients, although, more than half ultimately required intubation. Randomized controlled trials with this device are required to fully assess the efficacy of this interface.

Extracorporeal Membrane Oxygenation for COVID-19: Comparison of Outcomes to Non-COVID-19-Related Viral Acute Respiratory Distress Syndrome From the Extracorporeal Life Support Organization Registry.

To compare complications and mortality between patients that required extracorporeal membrane oxygenation (ECMO) support for acute respiratory distress syndrome (ARDS) due to COVID-19 and non-COVID-19 viral pathogens. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Nine-thousand two-hundred ninety-one patients that required ECMO for viral mediated ARDS between January 2017 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of interest were mortality during ECMO support and prior to hospital discharge. Time-to-event analysis and logistic regression were used to compare outcomes between the groups. Among 9,291 included patients, 1,155 required ECMO for non-COVID-19 viral ARDS and 8,136 required ECMO for ARDS due to COVID-19. Patients with COVID-19 had longer duration of ECMO (19.6 d [interquartile range (IQR), 10.1-34.0 d] vs 10.7 d [IQR, 6.3-19.7 d]; p < 0.001), higher mortality during ECMO support (44.4% vs 27.5%; p < 0.001), and higher in-hospital mortality (50.2% vs 34.5%; p < 0.001). Further, patients with COVID-19 were more likely to experience mechanical and clinical complications (membrane lung failure, pneumothorax, intracranial hemorrhage, and superimposed infection). After adjusting for pre-ECMO disease severity, patients with COVID-19 were more than two times as likely to die in the hospital compared with patients with non-COVID-19 viral ARDS. CONCLUSIONS: Patients with COVID-19 that require ECMO have longer duration of ECMO, more complications, and higher in-hospital mortality compared with patients with non-COVID-19-related viral ARDS. Further study in patients with COVID-19 is critical to identify the patient phenotype most likely to benefit from ECMO and to better define the role of ECMO in the management of this disease process.

Intensive Care and Organ Support Related Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis.

To perform a systematic review and meta-analysis to generate estimates of mortality in patients with COVID-19 that required hospitalization, ICU admission, and organ support. DATA SOURCES: A systematic search of PubMed, Embase, and the Cochrane databases was conducted up to December 31, 2021. STUDY SELECTION: Previously peer-reviewed observational studies that reported ICU, mechanical ventilation (MV), renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO)-related mortality among greater than or equal to 100 individual patients. DATA EXTRACTION: Random-effects meta-analysis was used to generate pooled estimates of case fatality rates (CFRs) for in-hospital, ICU, MV, RRT, and ECMO-related mortality. ICU-related mortality was additionally analyzed by the study country of origin. Sensitivity analyses of CFR were assessed based on completeness of follow-up data, by year, and when only studies judged to be of high quality were included. DATA SYNTHESIS: One hundred fifty-seven studies evaluating 948,309 patients were included. The CFR for in-hospital mortality, ICU mortality, MV, RRT, and ECMO were 25.9% (95% CI: 24.0-27.8%), 37.3% (95% CI: 34.6-40.1%), 51.6% (95% CI: 46.1-57.0%), 66.1% (95% CI: 59.7-72.2%), and 58.0% (95% CI: 46.9-68.9%), respectively. MV (52.7%, 95% CI: 47.5-58.0% vs 31.3%, 95% CI: 16.1-48.9%; p = 0.023) and RRT-related mortality (66.7%, 95% CI: 60.1-73.0% vs 50.3%, 95% CI: 42.4-58.2%; p = 0.003) decreased from 2020 to 2021. CONCLUSIONS: We present updated estimates of CFR for patients hospitalized and requiring intensive care for the management of COVID-19. Although mortality remain high and varies considerably worldwide, we found the CFR in patients supported with MV significantly improved since 2020.

Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study.

BACKGROUND: Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. METHODS: This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. RESULTS: 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6-24.0] J/min in patients with and 13.2 [10.2-18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3). CONCLUSION: A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.

Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial.

Background: An urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality. Methods: Using an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (<6 L/min oxygen for two consecutive days) and mortality. Data were evaluated biweekly in comparison to pre-specified criteria for graduation (i.e., likely efficacy), futility, and safety, with an adaptive sample size of 40-125 individuals per agent and a Bayesian analytical approach. Criteria were designed to achieve rapid screening of agents and to identify large benefit signals. Concurrently enrolled controls were used for all analyses. https://clinicaltrials.gov/ct2/show/NCT04488081. Findings: The first 7 agents evaluated were cenicriviroc (CCR2/5 antagonist; n = 92), icatibant (bradykinin antagonist; n = 96), apremilast (PDE4 inhibitor; n = 67), celecoxib/famotidine (COX2/histamine blockade; n = 30), IC14 (anti-CD14; n = 67), dornase alfa (inhaled DNase; n = 39) and razuprotafib (Tie2 agonist; n = 22). Razuprotafib was dropped from the trial due to feasibility issues. In the modified intention-to-treat analyses, no agent met pre-specified efficacy/graduation endpoints with posterior probabilities for the hazard ratios [HRs] for recovery ≤1.5 between 0.99 and 1.00. The data monitoring committee stopped Celecoxib/Famotidine for potential harm (median posterior HR for recovery 0.5, 95% credible interval [CrI] 0.28-0.90; median posterior HR for death 1.67, 95% CrI 0.79-3.58). Interpretation: None of the first 7 agents to enter the trial met the prespecified criteria for a large efficacy signal. Celecoxib/Famotidine was stopped early for potential harm. Adaptive platform trials may provide a useful approach to rapidly screen multiple agents during a pandemic. Funding: Quantum Leap Healthcare Collaborative is the trial sponsor. Funding for this trial has come from: the COVID R&D Consortium, Allergan, Amgen Inc., Takeda Pharmaceutical Company, Implicit Bioscience, Johnson & Johnson, Pfizer Inc., Roche/Genentech, Apotex Inc., FAST Grant from Emergent Venture George Mason University, The DoD Defense Threat Reduction Agency (DTRA), The Department of Health and Human ServicesBiomedical Advanced Research and Development Authority (BARDA), and The Grove Foundation. Effort sponsored by the U.S. Government under Other Transaction number W15QKN-16-9-1002 between the MCDC, and the Government.