Effectiveness of ACB-IP 1.0 Universal Pathogen Free Concentrated Cocktail Convalescent Plasma in COVID-19 Infection

BACKGROUNDThe efficacy of SARS-CoV2 single donor convalescent plasma (CP) varied according to the application time and the amount of antibody that is administered. Single donor CP has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the safety and efficacy of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled CP product was investigated. MATERIALS AND METHODSA total of sixteen patients were treated with either single donor CP (N:9) or pathogen-free, concentrated, pooled CP (ACB-IP 1.0) (N:7).RESULTSFive out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor CP. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor CP (0.9642) in 1:256 dilution (ρ<0.01)The mortality rates of the patients treated with ACB-IP 1.0 plasma were statistically lower (p< 0.05) than the patients treated with single donor CP. The administration of either single donor CP or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization (ρ< 0.01).CONCLUSIONThe present study established ACB-IP 1.0 plasma product as a safe and potentially effective treatment for COVID-19, allowing rapid access to patients in need.TRIAL REGISTRATIONTrial Registration Number: NCT04769245Trial Registration Date: 17.03.2021

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.

Immunotherapy in the Treatment of COVID-19

The high mortality rate in COVID-19 can be explained by the development of a hyperinflammatory syndrome, characterized by a cytokine storm and extensive thrombus formation. The main direction for preventing the development of hyperinflammatory syndrome and reducing mortality from COVID-19 is immune therapy, however, the data on the efficacy and criteria for prescribing immune drugs is very heterogeneous. The purpose of this review is to analyze the results of clinical trials on the use of various types of immune therapy and possible criteria for its prescription. Analysis of literature data showed that the most effective among the existing variants of immune therapy were monoclonal antibodies to IL-6, the use of donor plasma in the early stages of treatment. Janus kinase inhibitors, intravenous immunoglobulin improved the clinical characteristics of patients, but did not affect the mortality rate. An analysis of possible predictor-markers of the development of a cytokine storm revealed an increase in the number of neutrophils > 11 × 103/ml, a decrease in the number of lymphocytes > 1000 × 103/ml, an increase in the level of IL-6 > 24 pg/ml, LDH > 300 IU/L, D-dimer > 1000 ng/ml, and CRP > 10 mg/dL as the most informative and accessible in clinical practice at the moment.

No substantial pre-existing B cell immunity against SARS-CoV-2 in healthy adults

SummaryPre-existing immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. Various studies recently provided evidence of pre-existing T cell immunity against SARS-CoV-2 in unexposed individuals. In contrast, the presence and clinical relevance of a pre-existing B cell immunity remains to be fully elucidated. Here, we provide a detailed analysis of the B cell response to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated the memory B cell response to SARS-CoV-2 in 150 adults sampled pre-pandemically. Comprehensive screening of donor plasma and purified IgG samples for binding and neutralization in various functional assays revealed no substantial activity against SARS-CoV-2 but broad reactivity to endemic betacoronaviruses. Moreover, we analyzed antibody sequences of 8,174 putatively SARS-CoV-2-reactive B cells on a single cell level and generated and tested 158 monoclonal antibodies. None of the isolated antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of relevant pre-existing antibody and B cell immunity against SARS-CoV-2 in unexposed adults.

Characteristics of high titer convalescent plasma and antibody dynamics following administration in patients with severe COVID-19

We characterized the antibody composition of COVID-19 convalescent plasma (CCP) and the immunologic responses of hospitalized COVID-19 patients after receiving CCP or non-immune fresh frozen plasma (FFP). Despite selection of CCP with significantly higher total IgG than recipients, neutralizing antibody levels did not differ between donor plasma and CCP recipients.

Characteristics of convalescent plasma donors and their antibody titers in Bangladesh

Background: Convalescent plasma is considered a promising therapy for severe COVID-19 disease. It is collected from the voluntary donors. Measurement of the antibody titer is necessary before transfusion to predict the outcome in the recipients. Characteristics of the convalescent plasma donors in Bangladesh and their antibody titers are not known.Methods: Convalescent plasma was collected from the voluntary donors who survived the COVID-19 disease to transfuse to the severe COVID-19 patients under a randomized control trial. Total IgG antibody titer was measured in the donor plasma by indirect enzyme-linked immunosorbent assay. Data was collected in a preformed questionnaire before donor plasma collection.Results: The median age is 32 (18-55) years. Fever, cough, sore throat, diarrhea was most common among 68.3% of the symptomatic participants and the remaining 31.7% were asymptomatic at the time when they were RT-PCR positive. Overall, 57.1% of participants had mild symptoms, 11.1% had moderate symptoms and none had severe symptoms. Participants’ antibody titers were measured 41.68±14.072SD days after the RT-PCR positive date. Rapid qualitative test could not detect antibody in 11 (17.5%) potential donors. Of the remaining 52 (82.5%) antibody positive participants titer was measured in 43 participants and found 1:320 in 17 (27.0%) (n=63), 1:160 in another 17 (27.0%) (n=63) and 1:80 in rest of the 9 (14.28%) (n=63) Participants. The mean titer of the donors who were hospitalized during their illness (1:274.29) was statistically significantly higher (p=0.043, CI>95%). The mean titer was also higher in female than in male, symptomatic than asymptomatic participants and in donors of A positive blood group. However, these finding are not statistically significant. Antibody titer does not correlate with time of RT-PCR negativity from initial RT-PCR positivity, time from RT-PCR positivity to titer date, age and body mass index.Conclusions: All RT-PCR positive COVID-19 patients subsequently may not develop antibody. Although antibody titer among hospitalized symptomatic patients was significantly higher, further study is needed to recommend optimal convalescent plasma donor criteria.

THE EFFECTIVENESS OF ACB-IP 1.0 UNIVERSAL PATHOGEN FREE CONCENTRATED COCKTAIL CONVALESCENT PLASMA IN COVID-19 INFECTION

Introduction The efficacy of SARS-CoV2 standard single donor convalescent plasma varied according to the application time and most importantly the amount of antibody that is administered. Single donor plasma has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the efficacy and safety of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled convalescent plasma was investigated. Methods In this study, ACB-IP 1.0 convalescent plasma product was prepared as follows; first, convalescent plasma was collected from different donors, then pathogen-inactivation was carried-out, and isohemagglutinins were cryodepleted, respectively. Finally, concentrated convalescent plasma product was pooled and stored until use. A total of sixteen patients were treated with two different convalescent plasma products. Nine patients were treated with standard single donor convalescent plasma and seven were treated with pathogen-free, concentrated, pooled convalescent plasma (ACB-IP 1.0) between 01 March 2020 and 31 December 2020. The outcomes of these two plasma products were compared regarding SARS-CoV2 antibody titers, neutralizing antibody activities, length of hospitalization and mortality rates. Results Five out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor plasma. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor plasma (0.9642) in 1:256 dilution (ρ=0.0087) The mortality rate of the patients treated with ACB-IP 1.0 plasma showed statistically lower (p: 0,033) than the patients treated with single donor plasma. The administration of either single donor plasma or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization compared to administration of either plasma to the patients later than eight days (ρ= 0,0021) Discussion Pathogen-free, concentrated, pooled convalescent plasma may resolve the bias in SARS-CoV2 antibody titers and neutralizing antibody activities, without requiring blood group compatibility that allows patient accessibility in a shorter time and has safe plasma characteristic. This study indicates that ACB-IP 1.0 may be a superior product compared to standard single donor plasma.