Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection

BACKGROUNDThe efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODSThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer ([≥]1:320) CCP with standard plasma. Asymptomatic participants aged [≥]18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection. RESULTS180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups. CONCLUSIONIn this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection. Trial RegistrationClinicaltrial.gov number NCT04323800.

Mortality Associated With Intubation and Mechanical Ventilation in Patients with COVID-19

ObjectiveThe need for critical care, hemodynamic support, renal replacement therapy, and mechanical ventilation have emerged as key features of the SARS-nCoV-2 (COVID-19) pandemic. The primary aim of this study was to determine the in-hospital mortality rate of mechanically ventilated patients. We also sought to determine the risk of in-hospital mortality by age, gender, race, ethnicity, and body mass index. MethodsWe performed a retrospective cohort study to determine the mortality rate among inpatient adults with COVID-19 on mechanical ventilation in the Nuvance Health system between March 1, 2020 and July 17, 2020. Patients were included if they were 18 years or older, had a laboratory confirmed COVID-19 diagnosis, were admitted to hospitals within the Nuvance Health network (7 hospitals), and were on mechanical ventilation at any time during their inpatient stay. ResultsOverall mortality in our cohort of 304 patients was 53.3%. Multivariable logistic regression including age, gender, race, ethnicity, and BMI demonstrated patients over 71 years old had greater risk of mortality compared to patients ages 61-70, and females had half the risk compared to males. There was no significant difference in risk of mortality given race, ethnicity, or BMI. ConclusionsIn adult patients with confirmed COVID-19 infection requiring mechanical ventilation and intensive care, advanced age (>71 years old) and male gender are associated with increased risk of mortality. This information contributes to a collective body of evidence to support ongoing planning and decision-making among clinicians and for directed infection prevention programming.

Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in COVID-19

BackgroundThis study is the first of its kind to assess the impact of preemptive therapeutic dose anticoagulation on mortality compared to prophylactic anticoagulation among COVID-19 patients. Its findings provide insight to clinicians regarding the management of COVID-19, particularly with the known prothrombotic state. Research QuestionTo determine the impact of anticoagulation on in-hospital mortality among COVID-19 positive patients with the a priori hypothesis that there would be a lower risk of in-hospital mortality with use of preemptive therapeutic over prophylactic dose enoxaparin or heparin. Study Design and MethodsO_ST_ABSStudy DesignC_ST_ABSRetrospective cohort study from April 1 - April 25, 2020. The date of final follow-up was June 12, 2020. SettingTwo large, acute care hospitals in Western Connecticut. ParticipantFive hundred and one inpatients were identified after discharge as 18 years or older and positive for SARS-CoV-2. The final sample size included 374 patients after applying exclusion criteria. Demographic variables were collected via hospital billing inquiries, while the clinical variables were abstracted from patients medical records. ExposurePreemptive enoxaparin or heparin at a therapeutic or prophylactic dose. Main OutcomIn-hospital mortality. ResultsWhen comparing preemptive therapeutic to prophylactic anticoagulation through multi-variable analysis, risk of in-hospital mortality was 2.3 times greater in patients receiving preemptive therapeutic anticoagulation (95% CI = 1.0, 4.9; p = 0.04). InterpretationAn increase in in-hospital mortality was observed with preemptive therapeutic anticoagulation. Thus, in the management of COVID-19 and its complications, we recommend further research and cautious use of preemptive therapeutic over prophylactic anticoagulation.