Interferon-α2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19.

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG). STUDY DESIGN AND METHODS: Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases. RESULTS: Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels. CONCLUSIONS: Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

[Transfusion of convalescent plasma from patients with COVID -19]. / Transfusión de plasma convaleciente de pacientes con COVID-19.

There is currently no vaccine available and no specific medication against Coronavirus 2019 disease (COVID-19). The treatment is mainly based on support measures. In this context, several potentially useful therapies have been approved for use in clinical trials, such as convalescent plasma transfusion (CPT). PubMed was searched for studies on convalescent plasma and COVID-19, SARS or MERS. Studies on clinical efficacy in diseases caused by other coronaviruses (SARS-CoV and MERS-CoV) showed clinical improvement, increase of neutralizing antibodies, decreased mortality and absence of adverse events during and after treatment. We found 13 studies on this type of treatment used in patients with severe and critical COVID-19. Despite limitations regarding methodology, number of patients and the protocols for the analysis of donors' convalescent plasma, patients who received CPT showed clinical improvement, improvement of ventilatory patterns, resolution of lung injuries, decreased mortality, improvement of laboratory parameters, increase of neutralizing antibodies, decreased viral load and low frequency of adverse events.

Actualmente no existe vacuna disponible ni medicación específica contra la enfermedad por coronavirus 2019 (COVID-19). El tratamiento se basa fundamentalmente en medidas de soporte. En este contexto, se han aprobado múltiples terapias de potencial utilidad para su uso en ensayos clínicos, como la transfusión de plasma convaleciente (TPC). Se realizó una búsqueda en PubMed de estudios sobre plasma convaleciente y COVID-19, SARS o MERS. Los estudios sobre la eficacia clínica en enfermedades causadas por otros coronavirus (SARS-CoV y MERS-CoV) evidenciaron mejoría clínica, aumento de anticuerpos neutralizantes, disminución de la mortalidad y ausencia de eventos adversos durante y después del tratamiento. En el caso de la COVID-19, se encontraron 13 estudios en pacientes con la COVID-19 grave y crítica. Aunque existen limitaciones en la metodología, en el número de pacientes y en los protocolos para el análisis del plasma convaleciente de los donantes, los pacientes que recibieron TPC evidenciaron mejoría clínica, mejoría de patrones ventilatorios, resolución de lesiones pulmonares, disminución de mortalidad, mejoría de parámetros laboratoriales, aumento de anticuerpos neutralizantes, disminución de carga viral y baja frecuencia de eventos adversos.

Clinical outcomes for COVID-19 patients with diabetes mellitus treated with convalescent plasma transfusion in Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc on public health systems worldwide. The diagnosis of COVID-19 is well defined, but efficacious treatment is lacking. There is a big gap in knowledge regarding COVID-19 patients receiving convalescent plasma transfusion (CPT), especially those also suffering from diabetes mellitus (DM). In this study, among 3059 COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China, we documented the characteristics of 39 COVID-19 patients with DM receiving CPT and compared their baseline information and clinical outcomes to COVID-19 patients with DM receiving conventional treatment. We also performed the propensity-matched comparison of COVID-19 patients with DM between conventional treatment and CPT. The CPT was efficacious and beneficial for COVID-19 patients with DM, including severe or critically ill patients, without obvious adverse effects. Our data demonstrated that CPT significantly improved the clinical outcomes of COVID-19 patients with DM, especially the cure rate and duration of hospitalization compared with that in COVID-19 patients with DM receiving conventional treatment. This study not only provided a deeper understanding of characteristics in COVID-19 patients with DM receiving CPT but also highlighted the efficaciousness of CPT for COVID-19 patients with DM.

A Retrospective Study on the Effects of Convalescent Plasma Therapy in 24 Patients Diagnosed with COVID-19 Pneumonia in February and March 2020 at 2 Centers in Wuhan, China.

BACKGROUND This retrospective study aimed to describe the effects of convalescent plasma therapy in 24 patients diagnosed with coronavirus disease 2019 (COVID-19) pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during February and March 2020 in Wuhan, China. MATERIAL AND METHODS The confirmation of SARS-CoV-2 infection was made by the reverse transcription-polymerase chain reaction test. We retrospectively analyzed the clinical data and laboratory test reports of patients with severe COVID-19 pneumonia who received a convalescent plasma transfusion. RESULTS A total of 24 patients with COVID-19 pneumonia who were transfused with ABO-compatible convalescent plasma were enrolled in the study. Convalescent plasma transfusion showed an effective clinical outcome in 14 of 24 patients (an effective rate of 58.3%). No patients had an adverse reaction to the transfusion. Compared with before convalescent plasma transfusion, the lymphocyte count after convalescent plasma transfusion increased to a normal level (median: 0.80×109/L vs. 1.12×109/L, P=0.004). Other laboratory indicators such as white blood cells, high-sensitivity C-reactive protein, procalcitonin, alanine aminotransferase, and aspartate transaminase showed a decreasing trend after transfusion. CONCLUSIONS This retrospective observational clinical study showed that convalescent plasma therapy could have beneficial effects on patient outcomes. Recently, regulatory authorization has been given for the use of convalescent plasma therapy, and clinical guidelines have been developed for the collection and use of convalescent plasma and hyperimmune immunoglobulin in patients with COVID-19.

Transfusion support in COVID-19 patients: Impact on hospital blood component supply during the outbreak.

BACKGROUND: During the COVID-19 outbreak, most hospitals deferred elective surgical procedures to allow space for the overwhelming number of COVID-19 patient admissions, expecting a decrease in routine blood component requirements. However, because transfusion support needs of COVID-19 patients are not well known, its impact on hospital blood supply is uncertain. The objective of this study was to assess the effect of the COVID-19 pandemic on transfusion demand. STUDY DESIGN AND METHODS: Transfusion records during the peak of the COVID-19 pandemic (March 1-April 30, 2020) were reviewed in our center to assess changes in blood requirements. RESULTS: During this period 636 patients received a total of 2934 blood components, which reflects a 17.6% reduction in transfusion requirements with regard to the same period of 2019, and blood donations in Madrid dropped by 45%. The surgical blood demand decreased significantly during the outbreak (50.2%). Blood usage in the hematology and oncology departments remained unchanged, while the day ward demand halved, and intensive care unit transfusion needs increased by 116%. A total of 6.2% of all COVID inpatients required transfusion support. COVID-19 inpatients consumed 19% of all blood components, which counterbalanced the savings owed to the reduction in elective procedures. CONCLUSION: Although only a minority of COVID-19 inpatients required transfusion, the expected reduction in transfusion needs caused by the lack of elective surgical procedures is partially offset by the large number of admitted patients during the peak of the pandemic. This fact must be taken into account when planning hospital blood supply.

Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present herein the results of an interim analysis of 316 patients enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain IgG titer convalescent plasma is efficacious in early-disease patients.

A 63-Year-Old Woman with SARS-CoV-2 Infection, Who Developed Severe COVID-19 Pneumonia and Was Supported with Convalescent Plasma Therapy.

BACKGROUND There is no evidence-based treatment for coronavirus disease 2019 (COVID-19). We report the case of a 63-year-old woman with SARS-CoV-2 infection who developed severe COVID-19 pneumonia and was treated with convalescent plasma. CASE REPORT A 63-year-old woman who presented with severe and prolonged course of COVID-19 disease (fever up to 39.4°C, persistent cough, and dyspnea) received a convalescent plasma transfusion, which led to complete recovery. The diagnosis was confirmed by RT-PCR testing using the CFX96 Real-Time System (Bio-Rad, USA) from nasopharyngeal swabs. In laboratory tests, an increase in acute-phase parameters was observed. Chest computed tomography (CT) showed abnormalities typical for COVID-19. On days 9 and 11 of the disease, she received the convalescent plasma prepared from a single plasmapheresis donation from a male donor. This male donor was qualified as a convalescent plasma donor according to Polish guidelines, which are compliant with European guidelines. He donated plasma at the Regional Centre for Transfusion Medicine in Bialystok, Poland. The therapy with convalescent plasma led to clinical improvement and normalization of inflammatory parameters. CONCLUSIONS This report presents a case of severe COVID-19 pneumonia in a 63-year-old woman who was given supportive treatment with convalescent plasma. Ongoing clinical trials will determine whether convalescent plasma therapy is an effective treatment for SARS-CoV-2 infection.

Non-optimal effectiveness of convalescent plasma transfusion and hydroxychloroquine in treating COVID-19: a case report.

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in treating critically ill patients with COVID-19, and hydroxychloroquine could potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving combination therapy with CP transfusion and hydroxychloroquine for the first time. CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His temperature returned to normal and the OI ascended above 300 on day 11. Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission. CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.

Transfusion Thresholds for Adult Respiratory Extracorporeal Life Support: An Expert Consensus Document.

Severe acute respiratory distress syndrome (ARDS) can complicate novel pandemic coronavirus disease (COVID-19). Extracorporeal life support (ECLS) represents the final possible rescue strategy. Variations in practice, combined with a paucity of rigourous guidelines, may complicate blood-product resource availability and allocation during a pandemic. We conducted a literature review around venovenous extracorporeal membrane oxygenation (VV-ECMO) transfusion practices for platelets, packed red blood cells, fresh frozen plasma, prothrombin complex concentrate, and antithrombin. Pertinent society guidelines were examined, and the practice of Canadian ECLS experts was sampled through an environmental scan. This paper represents a synthesis of these explorations, combined with input from the Canadian Cardiovascular Critical Care (CANCARE) Society, Canadian Society of Cardiac Surgeons, and the Canadian Critical Care Society. We offer a pragmatic guidance document for restrictive transfusion thresholds in nonbleeding patients on VV-ECMO, which may attenuate transfusion-related complications and simultaneously shield national blood product inventory from strain during pandemic-induced activation of the National Plan for the Management of Shortages of Labile Blood Components.

Convalescent plasma to treat coronavirus disease 2019 (COVID-19): considerations for clinical trial design.

Case series studying convalescent plasma use in the treatment of COVID-19 have been promising, but additional, high-quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness. Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor. There are many clinical trials studying treatment of, and prophylaxis against, COVID-19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the "Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19" protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.