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.).

Convalescent Plasma Therapy in Severe COVID-19: A Pilot Study at the Beginning of the Pandemic Outbreak in Southern Chile.

Convalescent Plasma (CP) from patients who recovered from COVID-19 may present neutralizing antibodies against viral protein S of SARS-CoV-2 and emerged as a potential therapeutic alternative for patients with severe infection at the beginning of the COVID-19 pandemic breakout. Thus, this study aimed to evaluate the effect and safety of CP treatment in patients with severe COVID-19. METHODS: We designed a quasi-experimental study that included 156 patients with SARS-CoV-2 infection confirmed by RT-qPCR and severe symptoms who received CP. As a control group, we selected a historical cohort of 113 individuals admitted with COVID-19 and severe symptomatology before the starting date of the study. Clinical status and mortality during the study period were recorded. RESULTS: There were no adverse reactions to CP administration. In the CP group, days on mechanical ventilation were significantly lower than the control group (2.8±5.08 days vs. 4.7±6.19 days; p= 0.0081). Moreover, a significant difference was observed in the number of days stayed in the critical patient unit (CPU) in CP vs. controls (4.2±5.47 vs. 5.8±6.39 days, p= 0.0281). CONCLUSIONS: We observed no association between CP administration and survival at 14 days. Treatment with CP was safe and not associated with adverse events. In addition, using CP was associated with a reduction in both stay at the CPU and connection to mechanical ventilation.

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.

Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial.

BACKGROUND: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. METHODS: Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. RESULTS: Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test). CONCLUSIONS: Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

A Randomized Controlled Study Assessing Convalescent Immunoglobulins vs Convalescent Plasma for Hospitalized Patients With Coronavirus 2019.

BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19). METHODS: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients. RESULTS: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066). CONCLUSIONS: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Long-term antibody titers variation in unvaccinated patients receiving convalescent plasma or placebo for severe SARS-CoV-2 pulmonary infection.

BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Update on and Future Directions for Use of Anti-SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19.

As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti-SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti-SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.

Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection.

OBJECTIVES: Current evidence favors plasma to be effective against coronavirus disease 2019 (COVID-19) in critically ill patients in the early stages of infection. We investigated the safety and efficacy of convalescent plasma in specifically late-stage (designated as after 2 weeks of hospital admission) severe COVID-19 infection. We also conducted a literature review on the late-stage use of plasma in COVID-19. METHODS: This case series examined eight COVID-19 patients admitted to the intensive care unit (ICU) who met criteria for severe or life-threatening complications. Each patient received one dose (200 mL) of plasma. Clinical information was gathered in intervals of 1 day pretransfusion and 1 hour, 3 days, and 7 days posttransfusion. The primary outcome was effectiveness of plasma transfusion, measured by clinical improvement, laboratory parameters, and all-cause mortality. RESULTS: Eight ICU patients received plasma late in the course of COVID-19 infection, on average at 16.13 days postadmission. On the day before transfusion, the averaged initial Sequential Organ Failure Assessment (SOFA) score, PaO2:FiO2 ratio, Glasgow Coma Scale (GCS), and lymphocyte count were 6.5, 228.03, 8.63, and 1.19, respectively. Three days after plasma treatment, the group averages for the SOFA score (4.86), PaO2:FiO2 ratio (302.73), GCS (9.29), and lymphocyte count (1.75) improved. Although the mean GCS improved to 10.14 by posttransfusion day 7, the other means marginally worsened with an SOFA score of 5.43, a PaO2:FiO2 ratio of 280.44, and a lymphocyte count of 1.71. Clinical improvement was noted in six patients who were discharged from the ICU. CONCLUSIONS: This case series provides evidence that convalescent plasma may be safe and effective in late-stage, severe COVID-19 infection. Results showed clinical improvement posttransfusion as well as decreased all-cause mortality in comparison to pretransfusion predicted mortality. Randomized controlled trials are needed to conclusively determine benefits, dosage, and timing of treatment.

Convalescent plasma transfusion in severe COVID-19 patients: Clinical and laboratory outcomes.

INTRODUCTION: The objective of this study was to investigate the effect of convalescent plasma (CP) transfusion on clinical and serial laboratory parameters in severe COVID-19 patients. The Coronavirus Disease 2019 (COVID-19) pandemic presents a challenge to the healthcare system worldwide due to the limited treatment options available. The body of evidence reported that CP containing anti- COVID-19 antibodies could be effective against the infection. MATERIALS AND METHODS: This was a cross-sectional study that involved retrospective data collection of severe COVID-19 adult patients who received CP transfusion along with the best-of-care (CP group, n: 53) and best-of-care only (control group, n: 53). An age, gender, and comorbidity were manually matched approximately at a 1:1 ratio. RESULTS: The prevalence of adverse transfusion reactions was 5.7%. A shorter duration of oxygen support (median: 12 days vs 14 days, P=0.030) and a shorter duration of mechanical ventilation (median: 6 days vs 10 days, P=0.048) were found in the CP group. The laboratory parameters were also improved. However, there was no significant difference in the mechanical ventilation rate, length of hospital stay, length of intensive care unit (ICU) stay, and mortality rate across both groups (P = 0.492, 0.614, 0.793, 0.374). CONCLUSION: CP transfusion is safe and effective in the treatment of severe COVID-19 patients. However, a revision of our approaches such as early CP transfusion and use of a high-titre anti-COVID-19 neutralising antibody (nAb) unit is necessary to unlock the full potential benefits of CP transfusion among COVID-19 patients.

Convalescent plasma therapy in critically Ill COVID-19 patients: A retrospective cohort study.

Background: Convalescent plasma (CP) therapy can be defined as a passive immunity transfer approach involving the administration of plasma for therapeutic purposes to inpatients hospitalized due to an active virus infection. Passive immunity antibodies can reduce target organ damage and directly neutralize the responsible pathogens. A limited number of studies on the use of CP have reported that critically ill patients can benefit from CP therapy. Aim: We aimed in this study as the outcomes of CP therapy in critically ill coronavirus disease 2019 (COVID-19) patients in intensive care unit (ICU) and determine the differences between the recovery and mortality groups. Patients and Methods: This retrospective design study involved critically ill patients who were diagnosed with COVID-19 pneumonia or who were suspected of having COVID-19 in the ICU between April 1, 2020, and June 1, 2020. Comorbidity of patients, respiratory findings, hemodynamic data, laboratory data, and poor prognostic measures were compared between mortality and recovery group. Results: Convalescent plasma (CP) therapy was supplied for 41 (13.58%) patients in total of 302 COVID-19 patients. Twenty-nine patients were died in total of 41 COVID-19 patients who supplied CP therapy. The mortality rate is 70.73% in CP therapy. There was a significantly higher incidence (P < 0.021) of invasive mechanical ventilation (IMV) and significantly lower mean arterial pressure (MAP) values in mortality group (P < 0.05). There were significantly higher NLR values (P < 0.05), lower platelet count (P < 0.05), lower of glomerular filtration rate (GFR) level (P < 0.05), higher creatinine values (P < 0.05), higher lactate dehydrogenase (LDH) levels (P < 0.05), higher D-dimer levels (P < 0.05), higher level of pro-brain natriuretic peptide (BNP) (P = 0.000), rate of fever (P = 0.031), arrythmia (P = 0.024), and transfusion-associated circulatory overload (TACO) (P = 0.008) were more often in mortality group. Conclusion: Convalescent plasma therapy seems not useful in critically ill COVID-19 patients.

Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19). METHODS: Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. RESULTS: Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, -.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM. CONCLUSIONS: Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.

High-Dose Convalescent Plasma for Treatment of Severe COVID-19.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET).

BACKGROUND: Despite immunoglobulin replacement (IgRT) therapy, some patients with primary antibody deficiency (PAD) continue to develop respiratory infections. Recurrent and severe respiratory infections, particularly pneumonia, can lead to significant morbidity and mortality. Therefore, we sought to determine the risk factors of developing pneumonia in PAD patients, already receiving IgRT. METHODS: We evaluated clinical and laboratory features of PAD patients enrolled in the US Immune Deficiency Network (USIDNET) registry by April 2017. Patients were included if they met the following criteria: (1) PAD diagnosis (common variable immunodeficiency (CVID), agammaglobulinemia, hypogammaglobinemia, and specific antibody deficiency (SAD) and (2) available data on infections before and after IgRT. Patients were excluded if they were not receiving IgRT, or if no pre/post infections data were available. Descriptive and multivariable logistic regression analyses were used to identify factors associated with pneumonia post-IgRT. RESULTS: A total of 1232 patients met the inclusion criteria. Following IgRT, 218 patients (17.7%) were reported to have at least one pneumonia episode. Using multivariate logistic regression analysis, we found a statistically significant increased risk of pneumonia in patients with asthma (OR: 2.55, 95% CI (1.69-3.85), p < 0.001) bronchiectasis (OR: 3.94, 95% CI (2.29-6.80), p < 0.001), interstitial lung disease (ILD) (OR: 3.28, 95%CI (1.43-7.56), p < 0.005), splenomegaly (OR: 2.02, 95%CI (1.08-3.76), p < 0.027), allergies (OR: 2.44, 95% CI [1.44-4.13], p = 0.001), and patients who were not on immunosuppressives (OR: 1.61; 95%CI [1.06-2.46]; p = 0.027). For every 50 unit increase in IgA, the odds of reporting pneumonia post IgRT decreased (OR: 0.86, 95% CI [0.73-1.02], p = 0.062). Infectious organisms were reported in 35 of 218 patients who reported pneumonia after IgRT. Haemophilus influenzae was the most frequently reported (n = 11, 31.43%), followed by Streptococcus pneumoniae (n = 7, 20.00%). CONCLUSION: Our findings suggest PAD patients with chronic and structural lung disease, splenomegaly, and allergies were associated with persistent pneumonia. However, our study is limited by the cross-sectional nature of the USIDNET database and limited longitudinal data. Further studies are warranted to identify susceptible causes and explore targeted solutions for prevention and associated morbidity and mortality. CLINICAL IMPLICATIONS: Patients with primary antibody deficiency with structural lung disease, allergies, and splenomegaly are associated with persistent pneumonia post-IgRT.

Active surveillance of serious adverse events following transfusion of COVID-19 convalescent plasma.

BACKGROUND: The reported incidence of adverse reactions following Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) transfusion has generally been lower than expected based on the incidence of transfusion reactions that have been observed in studies of conventional plasma transfusion. This raises the concern for under-reporting of adverse events in studies of CCP that rely on passive surveillance strategies. MATERIALS AND METHODS: Our institution implemented a protocol to actively identify possible adverse reactions to CCP transfusion. In addition, we retrospectively reviewed the charts of inpatients who received CCP at Stanford Hospital between May 13, 2020 and January 31, 2021. We determined the incidence of adverse events following CCP transfusion. RESULTS: A total of 49 patients received CCP. Seven patients (14%) had an increased supplemental oxygen requirement within 4 h of transfusion completion, including one patient who was intubated during the transfusion. An additional 11 patients (total of 18, 37%) had increased oxygen requirements within 24 h of transfusion, including 3 patients who were intubated. Six patients (12%) fulfilled criteria for transfusion-associated circulatory overload (TACO). CONCLUSION: Using an active surveillance strategy, we commonly observed adverse events following the transfusion of CCP to hospitalized patients. It was not possible to definitively determine whether or not these adverse events are related to CCP transfusion. TACO was likely over-diagnosed given overlap with the manifestations of COVID-19. Nevertheless, these results suggest that the potential adverse effects of CCP transfusion may be underestimated by reports from passive surveillance studies.

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.