COVID-19 convalescent plasma utilization in the United States: data from the National Inpatient Sample.

COVID-19 convalescent plasma (CCP) use between October-December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations, and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance.

Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy.

INTRODUCTION: When the COVID-19 pandemic struck no specific therapies were available and many turned to COVID-19 convalescent plasma (CCP), a form of antibody therapy. The literature provides mixed evidence for CCP efficacy. AREAS COVERED: PubMed was searched using the words COVID-19 and convalescent plasma and individual study designs were evaluated for adherence to the three principles of antibody therapy, i.e. that plasma 1) contain specific antibody; 2) have enough specific antibody to mediate a biological effect; and 3) be administered early in the course of disease. Using this approach, a diverse and seemingly contradictory collection of clinical findings was distilled into a consistent picture whereby CCP was effective when used according to the above principles of antibody therapy. In addition, CCP therapy in immunocompromised patients is useful at any time in the course of disease. EXPERT OPINION: CCP is safe and effective when used appropriately. Today, most of humanity has some immunity to SARS-CoV-2 from vaccines and infection, which has lessened the need for CCP in the general population. However, COVID-19 in immunocompromised patients is a major therapeutic challenge, and with the deauthorization of all SARS-CoV-2-spike protein-directed monoclonal antibodies, CCP is the only antibody therapy available for this population.

Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1.

Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity. Here we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations (Vax) with or without recent Omicron COVID-19, as well as infection without vaccination (CCP) to determine level of BQ.1.* neutralizing antibodies and percent of plasma samples with neutralizing activity. More than 90 % of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, and BF.7 with 100 % neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50 % neutralizing titres (GM (GMT50) were 314, 78 and 204 for BQ.1.1, XBB.1 and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently (within 6 months) received at least a third vaccine dose had about half of the GM (GMT50) for all viral variants. Boosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, neutralizing antibody source against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.

COVID-19 Serology Data Provide Guidance for Future Deployments of Convalescent Plasma.

Measurement of antibody content and function after a viral illness is important for diagnosis and selection of the best convalescent plasma (CP) units for passive immunization. Zhang et al. (mBio 14:e03523-22, 2013, https://doi.org/10.1128/mbio.03523-22) analyzed over 19,000 coronavirus disease 2019 (COVID-19) CP (CCP) samples from the early days of the COVID-19 pandemic and reported a moderately strong correlation between antibody amount and neutralizing titer. Strikingly, about one-third of the samples had little or no neutralizing activity. The results provide a detailed glimpse of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunologically naive humans and reveal major differences in the quality of CP units collected for passive therapy before antibody screening. Heterogeneity in CCP quality undoubtedly contributed to the variable therapeutic efficacy. Analysis of the COVID-19 serology data suggest that, for the next infectious disease emergency, the best approach after quick establishment of methods for robust antibody-level stratification would be to use CP units in the top quintile of antibody content and neutralizing capacity.

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS: Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%-6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%-11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. CONCLUSIONS: Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.

Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

Absence of pathogenic viruses in COVID-19 convalescent plasma.

BACKGROUND: It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID-19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers. METHODS: The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay. RESULTS: TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS-CoV-2. DISCUSSION: There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non-pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). CONCLUSIONS: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. CLINICAL TRIALS REGISTRATION: NCT04373460.

Endemic Human Coronavirus Antibody Levels Are Unchanged after Convalescent or Control Plasma Transfusion for Early Outpatient COVID-19 Treatment.

The impact of preexisting antibodies to the four endemic human coronaviruses (ehCoV) (229E, OC43, NL63, and HKU1) on severe (hospitalization) coronavirus disease 2019 (COVID-19) outcomes has been described in small cohorts. Many studies have measured ehCoV 229E, OC43, NL63, and HKU1 antibody levels weeks after recovery rather than in the first weeks of illness, which is more relevant to early hospitalizations. Antibody levels to the spike protein of the four coronaviruses (229E, OC43, NL63, and HKU1), as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were measured both before and immediately after convalescent or control plasma transfusion in 51 participants who were hospitalized and 250 who were not hospitalized, as well as in 71 convalescent and 50 control plasma donors as a subset from a completed randomized controlled trial. In COVID-19 convalescent plasma donors, the ehCoV spike antibodies were 1.2 to 2 times greater than the control donor unit levels, while donor COVID-19 convalescent plasma (CCP) SARS-CoV-2 spike antibodies were more than 600 times the control plasma units. Plasma transfusion, whether COVID-19 convalescent or control, did not alter the post-transfusion antibody levels for the endemic human coronaviruses (229E, OC43, NL63, and HKU1) in those hospitalized and not hospitalized, despite the 1.2- to 2-fold elevation in donor COVID-19 convalescent plasma. There was no influence of prior antibody levels to 229E, OC43, NL63, and HKU1 or post-transfusion antibody levels on subsequent hospitalization. These data, from a well-controlled prospective randomized clinical trial, add evidence that antibodies to ehCoV do not significantly impact COVID-19 outcomes, despite the apparent back-boosting of some ehCoV after SARS-CoV-2 infection. IMPORTANCE The relevance of preexisting immunity to the four endemic human coronaviruses in the first week of COVID-19 illness on the outcome of COVID-19 progression stems from the high prevalence of the ehCoV and SARS-CoV-2 coronaviruses. The question has been raised of whether therapeutic convalescent plasma or control plasma containing ehCoV antibodies might alter the outcome of COVID-19 progression to hospitalization. Here, we observed that plasma transfusion did not significantly change the preexisting ehCoV antibody levels. In over 50 hospitalized participants and 250 nonhospitalized participants, ehCoV antibody levels were comparable, without statistical differences. Antibody levels were stable over the more than 12 months of the intervention trial, with individual heterogeneity similar in hospitalized and nonhospitalized participants. The ehCoV antibodies in plasma transfusion did not alter the recipient preexisting antibody levels nor hasten the COVID-19 progression to hospitalization in this clinical trial data.

Applying Gamification Principles and Therapeutic Movement Sequences to Design an Interactive Physical Activity Game: Development Study.

BACKGROUND: Depression is a severe illness that has accelerated with the spread of COVID-19 and associated lockdowns. As a result, reported physical activity has substantially decreased, further increasing depressive symptoms. OBJECTIVE: This study aims to explain the use of gamification principles to develop content for an interactive physical activity game for depression based on clinically proven depression diagnostic criteria. METHODS: We discuss related work in this field, the game design framework, the users' depression severity, how we customize the contents accordingly, the gradual progression of the game to match exercise principles, and user flow optimization. RESULTS: We provide a brief description of each of the games developed, including instructions on how to play and design aspects for flow, audio, and visual feedback methods. Exergames (interactive physical activity-based games) stimulate certain physical fitness factors such as improving reaction time, endurance, cardiovascular fitness, and flexibility. In addition, the game difficulty progresses based on various factors, such as the user's performance for successful completion, reaction time, movement speed, and stimulated larger joint range of motions. Cognitive aspects are included, as the user has to memorize particular movement sequences. CONCLUSIONS: Mental health issues are linked to behavior and movement; therefore, future physical activity-based interactive games may provide excellent stimulation for inducing user flow, while physical activity can help train various physical fitness factors linked to depression.

Proposal of a Novel Framework in Korea for a Total Safe-Care Fitness Solution in the COVID-19 Era

Physical activity is a crucial factor for maintaining not only physical health status, but vast amounts of research have shown its link with better mental health. Supporting the use of gyms for the safety of its practitioners is vital in the new norm and living with COVID-19. Therefore, in this study we show research supporting the development of a framework for a Total Safe-Care Fitness Solution based on a multimodal COVID-19 tracking system integrating computer vision and data from wearable sensors. We propose a framework with three areas that need to be integrated: a COVID-19 vaccine and health status recognition system (QR code scan prior to entry to the gym, and physiological signals monitored by a smart-band and a health questionnaire filled in prior to entry to the gym);an accident detection system (video and smart-band based);and a gym-user digital tracking system (CCTV and smart-band based). We show the proposed architecture for the integration of these systems and provide practical tips on how to implement it in testbeds for feasibility testing. To the best of our knowledge, this is the first proposed COVID-19 tracking system of use in gyms that includes a predictive model for accident detection for safer exercise participation through health monitoring.

The Potential Role of Passive Antibody-Based Therapies as Treatments for Monkeypox.

Monkeypox, a zoonosis caused by the orthopox monkeypox virus (MPXV) that is endemic to Central and West Africa, was previously linked to sporadic outbreaks and rare, travel-associated cases. An outbreak of monkeypox in 2022 has spurred a public health emergency of international concern, and this outbreak is unprecedented in terms of its scale and epidemiology. The outbreak has been focused overwhelmingly in men who have sex with men; however, the trajectory of the outbreak remains uncertain, with spread now being reported in women and children. The mortality has been low (<1%), yet the morbidity is high. Vaccines and oral antiviral agents that have been developed to protect against smallpox are available for use against monkeypox. However, the supply has been unable to match the demand during the outbreak. Passive antibody-based therapies, such as hyperimmune globulin (HIG), monoclonal antibodies, and convalescent plasma (CP), have been used against a diverse array of infectious diseases, culminating in their extensive use during the COVID-19 pandemic. Passive antibody-based therapies could play a role in the treatment of monkeypox, either as a temporizing role amid a shortfall in vaccines and antivirals or a complementary role to direct-acting antivirals. Drawing on the collective experience to date, there are regulatory, administrative, and logistical challenges to the implementation of antibody-based therapies. Their efficacy is contingent upon early administration and the presence of high-titer antibodies against the targeted pathogen. Research is needed to address questions pertaining to how to qualify HIG and CP and to determine their relative efficacy against MPXV, compared to antecedent therapies and preventative strategies. IMPORTANCE Monkeypox is an infection caused by the monkeypox virus (MPXV). The clinical findings in monkeypox include fever and rash. Historically, most cases of human monkeypox were reported in Africa. This changed in 2022, with a massive escalation in the number of cases across multiple countries, mainly affecting men who have sex with men. Although vaccines and oral antiviral medications are available for the treatment of monkeypox, their supply has been overwhelmed by the unprecedented number of cases. Antibody-based therapies (ABTs) have long been used to treat infectious diseases. They are produced in a laboratory or from plasma that has been collected from individuals who have recovered from an infection or have been vaccinated against that infection (in this case, monkeypox). ABTs could play a role in the treatment of monkeypox, either while awaiting oral medications or as a complementary treatment for patients that are at risk of severe disease.

Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources.

The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody titer units. Here, we systematically review Omicron-neutralizing plasma activity data, and report that approximately 47% (424/902) of CCP samples from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geometric mean of geometric mean titers for 50% neutralization GM(GMT50) of ~13, representing a > 20-fold reduction from WA-1 neutralization. Non-convalescent subjects who had received two doses of mRNA vaccines had a GM(GMT50) for Omicron BA.1 neutralization of ~27. However, plasma from vaccinees recovering from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT(50)) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had a GM(GMT50) > 450 for BA.4/5 and >1,500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and for future plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that escape therapeutic monoclonal antibodies.

Healthcare Worker Mental Health and Wellbeing During COVID-19: Mid-Pandemic Survey Results.

Introduction/Background: HealthCare worker (HCW) mental health and wellbeing are uniquely affected by the complexities of COVID-19 due to exposure to the virus, isolation from family and friends, risk and uncertainty. Little if any inquiry has examined the effects on an entire healthcare system, particularly immediately post-surge. We sought to examine the prevalence of psychiatric symptoms and behavioral health difficulties as a healthcare system transitioned out of the first wave. We assessed the effects of work role, setting and individual diversity factors on employee distress and coping strategies. Materials and Methods: This was an Institutional Review Board approved, unfunded, voluntary survey sent via REDCap link, to all employees of Hartford HealthCare, a mid-sized healthcare system (N ≈ 29,900) between May 15th and June 26th, 2020. Two system-wide emails and two emails targeting managers were sent during this time frame. Eight thousand four hundred and ninety four employees (28.4% of all e-mails distributed) participated in the survey, representing clinical, support, administrative, and medical staff across hospital, outpatient, residential, and business settings. The survey contained items assessing personal background, work environment/culture, and formal measures, including: patient health questionnaire-9 (PHQ-9), general anxiety disorder-7 (GAD-7), primary care post-traumatic stress disorder screen for DSM-5 (PC-PTSD), alcohol use disorders identification test (AUDIT-C), and the insomnia severity index (ISI). Results: Almost 1/3 of respondents (31%) reported symptoms of clinically significant anxiety; 83% moderate to severe depression; and 51% moderate to severe insomnia. Thirteen percent screened positive for post-traumatic stress disorder. Frontline staff (p ≤ 0.001 vs. others) and females (p < 0.001 vs. males) endorsed the highest levels of distress, while race (p ≤ 0.005) and ethnicity (p < 0.03 for anxiety, PTSD and insomnia) had a complex and nuanced interaction with symptoms. Conclusion: Pandemic stress effects all healthcare employees, though not equally. The effects of work role and environment are intuitive though critical. These data suggest individual diversity factors also play an important role in mental health and wellbeing. All must be considered to optimize employee functioning.

Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients.

BACKGROUND: Persistent viral RNA shedding of SARS-CoV-2 following COVID-19 has increasingly been recognized, with limited understanding of its implications on outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively assessed for persistent viral shedding across Northwestern Medicine Healthcare (NMHC) patients between March and August 2020. We assessed for predictors of persistent viral shedding, in-hospital delirium, and six-month mortality using binary logistic regression. RESULTS: Of the 2,518 hospitalized patients with an RT-PCR-confirmed diagnosis of COVID-19, 959 underwent repeat SARS-CoV-2 RT-PCR at least fourteen days from initial positive testing. Of those, 405 (42.2%) patients were found to have persistent viral shedding. Persistent viral shedding was associated with male sex, increased BMI, diabetes mellitus, chronic kidney disease, and exposure to corticosteroids during initial COVID-19 hospitalization. Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjusting for factors including severity of respiratory dysfunction (OR 2.45; 95% CI 1.75, 3.45). Even after adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding remained significantly associated with increased six-month mortality (OR 2.43; 95% CI 1.42, 4.29). CONCLUSIONS: Persistent viral shedding occurs frequently in hospitalized COVID-19 patients and is associated with in-hospital delirium and increased six-month mortality.

Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

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.