Outcomes of Extremely Prolonged (> 50 d) Venovenous Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure. DESIGN: Retrospective cohort study. SETTING: A large tertiary urban care center. PATIENTS: Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35-51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70-128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2-14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation. CONCLUSIONS: Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure.

Heart transplantation for COVID-19 myopathy in the United States.

Evidence on characteristics and outcomes of patients undergoing heart transplantation for coronavirus disease 2019 (COVID-19) associated cardiomyopathy is limited to case reports. Of all 6,332 patients aged ≥18 years undergoing heart transplantation from July 2020 through May 2022 in the United Network for Organ Sharing database, 12 (0.2%) patients had COVID-19 myocarditis and 98 (1.6%) patients with the same level of care had non-COVID-19 myocarditis. Their median age was 49 (range 19-74) years. All patients were hospitalized in the intensive care unit and 92.7% (n = 102) were on life support prior to transplantation. No patients with COVID-19 myocarditis required ventilation while waitlisted. Survival free from graft failure was 100% among COVID-19 patients and 88.5% among non-COVID-19 patients at a median of 257 (range 0-427) days post-transplant. These findings indicate that transplantation is rarely performed for COVID-19 related cardiomyopathy in the United States, yet early outcomes appear favorable in select patients.

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe ARDS From COVID-19.

RATIONALE: There are limited therapeutic options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. OBJECTIVES: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-induced respiratory failure. METHODS: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to standard of care. We hypothesized that cell therapy would be superior to sham-control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis. MEASUREMENTS AND MAIN RESULTS: At the third interim analysis, the Data and Safety Monitoring Board recommended that the trial halt enrollment as the pre-specified mortality reduction from 40% to 23% was unlikely to be achieved (n=222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (RR 0.88;95% CI 0.64,1.21;p=0.43). There were no significant differences in days alive off ventilation within 60 days (median rank 117.3 [IQR:60.0,169.5] in cell patients and 102.0 [IQR:54.0,162.5] in controls; higher is better). Resolution or improvement of ARDS at 30-days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) of control patients (OR 1.36;95% CI 0.57, 3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. CONCLUSIONS: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate/severe COVID-related acute respiratory distress syndrome. Clinical trial registration available at www. CLINICALTRIALS: gov, ID:NCT04371393. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Heart transplantation for COVID-19 myopathy in the United States

Evidence on characteristics and outcomes of patients undergoing heart transplantation for coronavirus disease 2019 (COVID-19) associated cardiomyopathy is limited to case reports. Of all 6332 patients aged ≥18 years undergoing heart transplant from July 2020 through May 2022 in the United Network for Organ Sharing database, 12 (0.2%) patients had COVID-19 myocarditis and 98 (1.6%) patients with the same level of care had non-COVID-19 myocarditis. Their median age was 49 (range 19-74) years. All patients were hospitalized in the intensive care unit and 92.7% (n=102) were on life support prior to transplantation. No patients with COVID-19 myocarditis required ventilation whilst waitlisted. Survival free from graft failure was 100% among COVID-19 patients and 88.5% among non-COVID-19 patients at a median of 257 (range 0-427) days post-transplant. These findings indicate that transplantation is rarely performed for COVID-19 related cardiomyopathy in the United States, yet early outcomes appear favorable in select patients.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

SARS-CoV-2-related outcomes after surgical procedures on SARS-CoV-2-positive patients in a large, urban, safety net medical center.

BACKGROUND: Beginning on March 16, 2020, nonurgent scheduled operations at a large, urban, safety net medical center were canceled. The purpose of this study was to determine complications associated with severe acute respiratory syndrome coronavirus 2 infection for all operations done from March 16 to June 30, 2020. STUDY DESIGN: This study was a single-institution, retrospective observational analysis of data for all surgical procedures and all severe acute respiratory syndrome coronavirus 2 tests done in the medical center from March 16 to June 30, 2020. The charts of all severe acute respiratory syndrome coronavirus 2-positive patients who had a surgical procedure during the study time period were retrospectively reviewed to assess the outcomes. RESULTS: Of 2,208 operations during that time, 29 (1.3%) patients were severe acute respiratory syndrome coronavirus 2-positive and were asymptomatic at the time of their operations. Twenty-four (82.7%) of the 29 required urgent or emergent procedures. The median time between availability of test results and operations for these patients was 0.63 + 1.94 days. With median follow-up of 89 days, none of the 29 patients died from severe acute respiratory syndrome coronavirus 2-related causes, and none developed clinically evident thromboembolism or required reintubation secondary to severe acute respiratory syndrome coronavirus 2-related pneumonia. CONCLUSION: By operating on carefully screened, asymptomatic severe acute respiratory syndrome coronavirus 2-positive patients, it was possible to eliminate major complications and mortality due to severe acute respiratory syndrome coronavirus 2 infection.

Mortality and Readmission Rates Among Patients With COVID-19 After Discharge From Acute Care Setting With Supplemental Oxygen.

Importance: To optimize patient outcomes and preserve critical acute care access during the COVID-19 pandemic, the Los Angeles County Department of Health Services developed the SAFE @ HOME O2 Expected Practice (expected practice), enabling ambulatory oxygen management for COVID-19. Objective: To assess outcomes of patients with COVID-19 pneumonia discharged via the expected practice approach to home or quarantine housing with supplemental home oxygen. Design, Setting, and Participants: This retrospective cohort study included 621 adult patients with COVID-19 pneumonia who were discharged from 2 large urban public hospitals caring primarily for patients receiving Medicaid from March 20 to August 19, 2020. Patients were included in the analysis cohort if they received emergency or inpatient care for COVID-19 and were discharged with home oxygen. Interventions: Patients receiving at least 3 L per minute of oxygen, stable without other indication for inpatient care, were discharged from either emergency or inpatient encounters with home oxygen equipment, educational resources, and nursing telephone follow-up within 12 to 18 hours of discharge. Nurses provided continued telephone follow up as indicated, always with physician back-up. Main Outcomes and Measures: All-cause mortality and all-cause 30-day return admission. Results: A total of 621 patients with COVID-19 pneumonia (404 male [65.1%] and 217 female [34.9%]) were discharged with home oxygen. Median age of these patients was 51 years (interquartile range, 45-61 years), with 149 (24.0%) discharged from the emergency department and 472 (76%) discharged from inpatient encounters. The all-cause mortality rate was 1.3% (95% CI, 0.6%-2.5%) and the 30-day return hospital admission rate was 8.5% (95% CI, 6.2%-10.7%) with a median follow-up time of 26 days (interquartile range, 15-55 days). No deaths occurred in the ambulatory setting. Conclusions and Relevance: In this cohort study, patients with COVID-19 pneumonia discharged on home oxygen had low rates of mortality and return admission within 30 days of discharge. Ambulatory management of COVID-19 with home oxygen has an acceptable safety profile, and the expected practice approach may help optimize outcomes, by ensuring right care in the right place at the right time and preserving access to acute care during the COVID-19 pandemic.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).

Rapid Adaptation of a Surgical Research Unit to Conduct Clinical Trials During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has brought most ongoing clinical trials to a standstill, while at the same time emphasizing the need for new therapeutic treatments and strategies to mitigate the morbidity and mortality related to COVID-19. Recent publication of several observational studies has generated much discussion surrounding efficacy of drugs including hydroxychloroquine, azithromycin, and remdesivir, stressing the need for high-quality prospective, randomized control trials in patients with COVID-19. Ongoing "stay at home" orders and institutional policies mandating "work from home" for nonessential employees, which includes most research personnel, have impacted the ability to implement and conduct clinical studies. This article discusses the approach of an experienced clinical trials unit to make adjustments for ongoing studies and ensure the safety of study participants. At the same time, plans were implemented to continue collection of data to achieve endpoints, safely enroll and follow participants in studies offering potential benefit, and quickly implement new COVID-19 clinical trials. The existence of a Division of Clinical Research with regulatory, budgeting, contracting, and coordinating expertise within a department of surgery can successfully accommodate a crisis situation and rapidly adapt to new requirements for the safe, efficient, and effective conversion to a remote work force without compromising the research process.