UNASSIGNED: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients.
UNASSIGNED: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections.
UNASSIGNED: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days.
UNASSIGNED: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

BACKGROUND: There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.
METHODS: The study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as \'dose\' of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation.
RESULTS: A total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28).
CONCLUSIONS: Higher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.

BACKGROUND: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic.
CONCLUSIONS: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.
Введение. При возникновении нового заболевания одним из наиболее доступных средств с установленной и доказанной терапевтической эффективностью в первую очередь являются препараты, содержащие специфические антитела к данному инфекционному агенту. Введение таких препаратов направлено на снижение количества возбудителя в макроорганизме и, как следствие, уменьшение тяжести симптомов заболевания либо выздоровление. Целью настоящего обзора является анализ опыта использования иммуноглобулинов и моноклональных антител при лечении больных COVID-19 в ходе пандемии. Результаты и заключение. Двумя основными группами медицинских средств защиты, блокирующих проникновение вируса SARS-CoV-2 в пермиссивные клетки, являются препараты, получаемые из плазмы крови реконвалесцентов (иммуноглобулин), и человеческие моноклональные антитела. В первой группе препаратов при лечении больных COVID-19 ведущее место занимает плазма крови реконвалесцентов. Данный препарат с успехом может быть использован для проведения экстренной профилактики на ранних стадиях заболевания. Основным недостатком терапии при использовании плазмы крови реконвалесцентов является трудность стандартизации ввиду значительного варьирования содержания специфических антител у доноров. Другим недостатком терапии при использовании препаратов первой группы являются нежелательные побочные реакции у реципиентов, возникающие при их введении. Альтернативным подходом при проведении терапии COVID-19 является использование гуманизированных и генно-инженерных человеческих моноклональных антител против определенных эпитопов вируса SARS-CoV-2, в частности, рецептор-связывающего домена S-белка, способных предотвратить проникновение вируса в пермиссивные клетки и прервать развитие манифестной инфекции. Преимуществами данных препаратов является их безопасность, высокая специфическая активность, возможность стандартизации, однако сложность их производства и высокая стоимость делают их малодоступными для массового использования в практической медицине.

The case of clinical trials for convalescent plasma during COVID-19 illustrates important lessons for realizing public sector approaches to biomedical research and development. These lessons, centering on mission, transparency, and spillover effects, can be translated to wider efforts to develop a \"public option\" for clinical trials.

Interventional clinical studies of convalescent plasma to treat COVID-19 were predominantly funded and led by public sector actors, including blood services operators. We aimed to analyze the processes of clinical studies of convalescent plasma to understand alternatives to pharmaceutical industry biopharmaceutical research and development, particularly where public sector actors play a dominant role. We conducted a qualitative, critical case study of purposively sampled prominent and impactful clinical studies of convalescent plasma during 2020-2021.

BACKGROUND: COVID-19 claimed millions of lives, mainly in the pre-vaccine era. Preliminary studies showed promising efficacy of convalescent plasma against SARS-CoV-2 (CP).
OBJECTIVE: To evaluate the efficacy of CP in patients hospitalized for COVID-19 with moderate severity.
METHODS: Retrospective, bicentric study including adults hospitalized for moderate (non-critical) COVID-19 who required oxygen therapy. CP donated by survivors of mild cases (600 cc) were searched for IgG anti-SARS-CoV-2. Its impact on mortality, hospital stay (days), and need for mechanical ventilation (IMV) was evaluated.
RESULTS: Of the 119 patients included, 58% were men (median age 60 years), 88% had comorbidity, and 43% had a high-risk CALL score. Forty-three patients (36%) received CP, only 15 (12.6%) early (< 7 days). Twenty-two patients had to be transferred to the intensive care unit; 18 received IMV, and 15 died (12.6%). The use of CP was not associated with changes in mortality (p = 0.16), need for IMV (p = 0.79), or hospital stay (p = 0.24). Its early administration (< 7 days of symptoms) did not show a significant association either. The presence of heart disease and subsequently requiring IMV were independent factors of mortality.
CONCLUSIONS: The use of CP in patients hospitalized for moderately severe COVID-19 was not associated with lower mortality, hospital stay, or the need for IMV.

Blood transfusion capacity in low- and middle-income countries (LMICs), encompassing both the safety and adequacy of the blood supply, is limited. The challenges facing blood banks in LMICs include regulatory oversight, blood donor selection, collection procedures, laboratory testing, and post-transfusion surveillance. A high proportion of LMICs are unable to fully meet clinical demands for blood products, and many do not meet even the minimum threshold of collection (10 units per 1000 population). Suboptimal clinical transfusion practices, in large part due to a lack of training in transfusion medicine, contribute to blood wastage. During the COVID-19 pandemic, high- and LMICs alike experienced blood shortages, in large part due to quarantine and containment measures that impeded donor mobility. COVID-19 convalescent plasma (CCP) was particularly appealing for the treatment of patients with COVID-19 in LMICs, as it is a relatively inexpensive intervention and makes use of the existing blood collection infrastructure. Nonetheless, the challenges of using CCP in LMICs need to be contextualized among broad concerns surrounding blood safety and availability. Specifically, reliance on first time, family replacement and paid donors, coupled with deficient infectious disease testing and quality oversight, increase the risk of transfusion transmitted infections from CCP in LMICs. Furthermore, many LMICs are unable to meet general transfusion needs; therefore, CCP collection also risked exacerbation of pervasive blood shortages.

OBJECTIVE: Initial therapeutic efforts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included the use of plasma from convalescent donors containing anti-SARS-CoV-2 antibodies. High-neutralizing antibody titres are required for therapeutic efficacy. This study aims to show that immunoadsorption followed by tangential flow filtration can be used to obtain antibody concentrates with high-neutralizing capacities.
METHODS: Eligible donors (n = 10, five males and three females) underwent immunoadsorption using adsorber columns specific for human antibodies. Glycine-washed out eluates of 1.5 L volume were further concentrated by tangential flow filtration using 30 kDa ultrafiltration membranes. The same membranes were applied for diafiltrations to exchange residual glycine for 0.9% normal saline.
RESULTS: Antibody concentrates were obtained within 8 h from the start of donation and had 4.58 ± 1.95, 3.28 ± 1.28 and 2.02 ± 0.92 times higher total IgG, IgA and IgM concentrations, 3.29 ± 1.62 and 3.74 ± 0.6 times higher SARS-CoV-2 N and S antibody concentrations and 3.85 ± 1.71 times higher SARS-CoV-2 S-specific IgG concentrations compared to the donors\' peripheral blood. The specific SARS-CoV-2 virus neutralization capacities increased in all but one concentrate. All antibody concentrates (50-70 mL final volume) passed microbiological tests, were free of hazardous glycine levels and could be stored at -80°C and 4°C for 1 year with 20 ± 3% antibody loss.
CONCLUSIONS: Immunoadsorption followed by tangential flow filtration is a feasible procedure to collect IgG, IgA and IgM as well as SARS-CoV-2 N- and S-specific antibody concentrates of low volume, free of albumin and coagulation factors. Whether these concentrates can be used as passive immunisation in infected patients remains to be elucidated.

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.

Immunocompromised patients are at high risk to fail clearance of SARS-CoV-2. Prolonged COVID-19 constitutes a health risk and a management problem as cancer treatments often have to be disrupted. As SARS-CoV-2 evolves, new variants of concern have emerged that evade available monoclonal antibodies. Moreover, antiviral therapy promotes SARS-CoV-2 escape mutations, particularly in immunocompromised patients. These patients frequently suffer from prolonged infection. No successful treatment has been established for persistent COVID-19 infection. Here, we report on a series of 21 immunocompromised patients with COVID-19-most of them hematologic malignancies-treated with plasma obtained from recently convalescent or vaccinated donors or a combination thereof. Repeated dosing of SARS-CoV-2-antibody-containing plasma could clear SARS-CoV-2 infection in 16 out of 21 immunocompromised patients even if COVID-19-specific treatments failed to induce sustained viral clearance or to improve clinical course of SARS-CoV-2 infection. Ten patients were major responders defined as an increase delta(d)Ct of > = 5 after the first administration of convalescent and/or vaccinated plasma (C/VP). On average, SARS-CoV-2 PCR Ct values increased from a median value of 22.55 (IQR = 19.10-24.25) to a median value of 29.57 (IQR = 27.55-34.63; p = <.0001) in the major response subgroup. Furthermore, when treated a second time with C/VP, even 4 out of 5 of the initial nonresponders showed an increase in Ct-values from a median value of 23.13 (IQR = 17.75-28.05) to a median value of 32.79 (IQR = 31.75-33.75; p = .013). Our results suggest that C/VP could be a feasible treatment of COVID-19 infection in patients with hematologic malignancies who did not respond to antiviral treatment.