Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58). INTERPRETATION: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04362176; URL: www. CLINICALTRIALS: gov.

Orthotopic Liver Transplantation in a Cirrhotic Patient With Recent COVID-19 Infection.

The coronavirus disease 2019 (COVID-19) pandemic has led to a decrease in liver transplantation because of concerns regarding safety and healthcare resource utilization. There are scant data regarding the safety, optimal timing, and preferred postsurgical immunosuppression regimens for liver transplantation in patients recovered from COVID-19 infection. We describe our experience with one of the first reported cases of orthotopic liver transplantation in a patient who had recently recovered from COVID-19 infection. Using our experience as an example, orthotopic liver transplantation in patients that have recovered from COVID-19 may be safe.

Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. METHODS: This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514. FINDINGS: Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups. INTERPRETATION: There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed. FUNDING: Kiniksa Pharmaceuticals.

Daptomycin-Induced Acute Eosinophilic Pneumonia.

Antibiotic use in pneumonia is a common practice globally when there is suspicion for bacterial involvement. However, there have been few instances where the treatment is the cause of pulmonary symptoms, manifesting as so-called "multifocal pneumonia." Daptomycin is one of the main antibiotics known to have several adverse effects, including drug-induced pulmonary eosinophila. We present the case of a patient with probable daptomycin-induced acute eosinophilic pneumonia. Stopping the offending agent and concomitant steroid therapy resulted in resolution of symptoms and prevention of worsening respiratory distress.

Results of preoperative screening for COVID-19 correlate with the incidence of infection in the general population -a tertiary care experience.

Objectives: Many hospitals have recently instituted policies mandating preoperative COVID-19 testing. However, it is uncertain whether institutions can dictate such policies based on infection rates found in the general population. Therefore, the main aims of the study were to determine (1) what proportion of preoperative patients tested positive, (2) what percentage was asymptomatic, and (3) whether variations throughout time in numbers of positive patients reflected changes observed in our state.Methods: All COVID-19 preoperative screening tests (nasopharyngeal-swab RT-PCR testing) performed in our hospital between 04/13/2020 and 08/27/2020 were retrospectively reviewed. The unit of analysis was number of patients who tested negative/positive. Medical records of positive patients were reviewed to determine the presence of COVID-19 symptoms. A curve was created showing our number of positive patients per week and another one presenting the number of positive patients per day in Florida, both figures were compared.Results: A total of 7,213 patients from all specialties were preoperatively tested, out of which 85 were positive for an overall infection rate of 1.2%. In 18% (15/85) of positive patients, it was not possible to determine symptomatology. Among remaining patients, 49% (34/70) were asymptomatic while 51% (36/70) were symptomatic for COVID-19. Peak of positive cases occurred in mid-July in both curves, and the upward and downward tendencies in positive numbers mirrored each other.Conclusion: COVID-19 infection rate among our preoperative patients was very low. Nearly 50% of positive patients were asymptomatic. Our data suggest that a tertiary hospital can promulgate COVID-19 preoperative screening policies based on infection trends observed in the general population. However, in addition to the test, patients should be encouraged to self-quarantine for 14 days before surgery.

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.

Successful mobile extracorporeal membrane oxygenator for COVID-19 severe respiratory failure.

High volume extracorporeal membrane oxygenation (ECMO) centers have developed mobile ECMO programs in recent years to facilitate the implementation of ECMO support at hospitals with lower capabilities, and transfer these patients for further care. We report a case of mobile ECMO on a patient with coronavirus disease 2019-related acute respiratory distress syndrome, and discuss the potential application in the current severe acute respiratory syndrome coronavirus 2 pandemic.

Clinical Features of Respiratory Viral Infections Among Inpatients at a Major US Tertiary Care Hospital.

OBJECTIVES: Respiratory viral illnesses (RVI) are reliably diagnosed by respiratory viral panel using polymerase chain reaction (RVP-PCR); however, owing to the scant data, clinical presentation alone is unreliable in establishing viral etiology. The primary objective of this study was to characterize signs and symptoms of RVI among inpatients in a major tertiary care hospital. METHODS: Between 2013 and 2015, adult inpatients with RVI undergoing RVP-PCR were prospectively enrolled in our study. Clinical data were collected by interviews and electronic medical record reviews. Data analysis was performed using χ(2) testing, analysis of variance for continuous variables, and logistic regression modeling. RESULTS: Of 421 patients analyzed, 175 (41.7%) had a positive RVP-PCR. Patients were evenly matched at baseline except for renal disease. Multivariate logistic regression modeling demonstrated the following positive correlations: positive RVP-PCR with renal disease (odds ratio [OR] 2.08), cough (OR 2.28), and wheezing (OR 1.8); influenza with cough (OR 5.04), and renal disease (OR 2.17); metapneumovirus with age older than 65 (OR 3.24); respiratory syncytial viruses with wheezing (OR 3.42) and immunosuppression (OR 3.11); and parainfluenza with smoking (OR 3.16). Negative correlations included influenza with anosmia (OR 0.41); rhinovirus/enterovirus with feeling confined to bed (OR 0.3); metapneumovirus with smoking (OR 0.29); and parainfluenza with male sex (OR 0.22). CONCLUSIONS: In this descriptive study, we noted specific viral associations with clinical signs and symptoms among 421 inpatients with RVIs. With increasing RVP-PCR use, studies similar to ours may be able to better define the clinical presentation of RVIs and lead to evidence-based, clinical presentation-guided diagnostic and management algorithms.

Incidence of extended-spectrum-ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates that test susceptible to cephalosporins and aztreonam by the revised CLSI breakpoints.

The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or ≥1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBL-producing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates).