COVID-19 Outcomes in a US Cohort of Persons Living with HIV (PLWH).

Reported coronavirus disease 2019 (COVID-19) outcomes in persons living with HIV (PLWH) vary across cohorts. We examined clinical characteristics and outcomes of PLWH with COVID-19 compared with a matched HIV-seronegative cohort in a mid-Atlantic US healthcare system. Multivariate logistic regression was used to explore factors associated with hospitalization and death/mechanical ventilation among PLWH. Among 281 PLWH with COVID-19, the mean age was 51.5 (SD 12.74) years, 63% were male, 86% were Black, and 87% had a HIV viral load <200 copies/mL. Overall, 47% of PLWH versus 24% (p < 0.001) of matched HIV-seronegative individuals were hospitalized. Rates of COVID-19 associated cardiovascular and thrombotic events, AKI, and infections were similar between PLWH and HIV-seronegative individuals. Overall mortality was 6% (n = 18/281) in PLWH versus 3% (n = 33/1124) HIV-seronegative, p < 0.0001. Among admitted patients, mortality was 14% (n = 18/132) for PLWH and 13% (n = 33/269) for HIV-seronegative, p = 0.75. Among PLWH, hospitalization associated with older age aOR 1.04 (95% CI 1.01, 1.06), Medicaid insurance aOR 2.61 (95% CI 1.39, 4.97) and multimorbidity aOR 2.98 (95% CI 1.72, 5.23). Death/mechanical ventilation associated with older age aOR 1.06 (95% CI 1.01, 1.11), Medicaid insurance aOR 3.6 (95% CI 1.36, 9.74), and multimorbidity aOR 4.4 (95% CI 1.55, 15.9) in adjusted analyses. PLWH were hospitalized more frequently than the HIV-seronegative group and had a higher overall mortality rate, but once hospitalized had similar mortality rates. Older age, multimorbidity and insurance status associated with more severe outcomes among PLWH suggesting the importance of targeted interventions to mitigate the effects of modifiable inequities.

Transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection: a double-blinded, phase 2 randomized, controlled trial.

BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) 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 new SARS-CoV-2 infection. RESULTS: 180 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 screening SARS-CoV-2 RT-PCR positivity. 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. 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) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Rapid Deployment of a Free, Privacy-Assured COVID-19 Symptom Tracker for Public Safety During Reopening: System Development and Feasibility Study.

BACKGROUND: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of cases of coronavirus disease (COVID-19) in the United States has exponentially increased. Identifying and monitoring individuals with COVID-19 and individuals who have been exposed to the disease is critical to prevent transmission. Traditional contact tracing mechanisms are not structured on the scale needed to address this pandemic. As businesses reopen, institutions and agencies not traditionally engaged in disease prevention are being tasked with ensuring public safety. Systems to support organizations facing these new challenges are critically needed. Most currently available symptom trackers use a direct-to-consumer approach and use personal identifiers, which raises privacy concerns. OBJECTIVE: Our aim was to develop a monitoring and reporting system for COVID-19 to support institutions conducting monitoring activities without compromising privacy. METHODS: Our multidisciplinary team designed a symptom tracking system after consultation with experts. The system was designed in the Georgetown University AvesTerra knowledge management environment, which supports data integration and synthesis to identify actionable events and maintain privacy. We conducted a beta test for functionality among consenting Georgetown University medical students. RESULTS: The symptom tracker system was designed based on guiding principles developed during peer consultations. Institutions are provided access to the system through an efficient onboarding process that uses clickwrap technology to document agreement to limited terms of use to rapidly enable free access. Institutions provide their constituents with a unique identifier to enter data through a web-based user interface to collect vetted symptoms as well as clinical and epidemiologic data. The website also provides individuals with educational information through links to the COVID-19 prevention recommendations from the US Centers for Disease Control and Prevention. Safety features include instructions for people with new or worsening symptoms to seek care. No personal identifiers are collected in the system. The reporter mechanism safeguards data access so that institutions can only access their own data, and it provides institutions with on-demand access to the data entered by their constituents, organized in summary reports that highlight actionable data. Development of the system began on March 15, 2020, and it was launched on March 20, 2020. In the beta test, 48 Georgetown University School of Medicine students or their social contacts entered data into the system from March 31 to April 5, 2020. One of the 48 users (2%) reported active COVID-19 infection and had no symptoms by the end of the monitoring period. No other participants reported symptoms. Only data with the unique entity identifier for our beta test were generated in our summary reports. CONCLUSIONS: This system harnesses insights into privacy and data sharing to avoid regulatory and legal hurdles to rapid adaption by entities tasked with maintaining public safety. Our pilot study demonstrated feasibility and ease of use. Refinements based on feedback from early adapters included release of a Spanish language version. These systems provide technological advances to complement the traditional contact tracing and digital tracing applications being implemented to limit SARS-CoV-2 transmission during reopening.