Objective: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). Trial Design and Participants: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24–48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. Interventions: The intervention group participants were infused 300 ml (200–400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. Outcomes: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. Results: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299–1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. Conclusion: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. Trial Registration: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.

Background The COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. Objective The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. Methods Eligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance. Results At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. Conclusions In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. Trial Registration ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681 International Registered Report Identifier (IRRID) PRR1-10.2196/23543

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Hepatitis B virus (HBV) is a significant cause of transfusiontransmitted infections. To achieve entirely HBV-safe transfusion still appears to be an unreachable objective, at least in the high-prevalence regions of the developing world. Transfusionrelated HBV safety depends on the screening technique adopted by the blood banks and its prevalence in the community, and the more sensitive the screening technique adopted the less the chance of transmitting HBV infection through the transfusion (1). All endeavors towards lowering the risk of transfusion transmitted HBV and/or HCV infection play an important role in prevention of this preventable human suffering. This is particularly significant in the developing countries with limited resources and overstretched health budgets. A recently published report by Dineva et al. is a remarkable achievement in this direction (2). The authors have introduced a simple, sensitive, instrument-independent technique for visual detection of multiple nucleic acid hybridization on the dipstick membrane. The report shows high sensitivity and reproducibility of the test for detection of HBV DNA, HCV RNA, and human immunodeficiency virus RNA among blood donors by minipools. Unfortunately, the genomic screening technology is still expensive and not affordable for the developing regions of the world where these viruses are highly endemic, which not only increases the risk of transfusion-transmitted HBV and/or HCV infection but is perhaps an important mode of spread of this infection. Most of the developing countries are screening the collected units of blood for HBsAg, anti-HBc, anti-HBs, and anti-HCV by enzyme immunoassay. The blood units which are anti-HBc positive or anti-HCV positive are rejected, thus leading to high rejection rates of collected units of blood. At this center, 3.2% of units are rejected because of isolated anti-HBc positivity (4). The rejection of these invaluable collected blood units and exclusion of the munificent volunteer blood donors because of isolated anti-HBc or anti-HCV positivity lead to chronic shortage of blood. The blood units which are isolated as being anti-HBc positive may not necessarily contain HBV DNA when tested by the nucleic acid amplification testing (NAT) technology, or anti-HCV-positive units may not be positive for HCV RNA if tested by PCR. Hence, they can perhaps be utilized if the low-cost genomic screening resources are made available to the developing countries; on the other hand, the anti-HBcand/or anti-HBs-positive donors might be positive for HBV DNA if tested by the sensitive NAT assay system (3, 5). The visual detection dipstick method for detection of HBV and HCV nucleic acid appears an attractive alternative to the intricate instrument-dependent methods for the countries with limited resources. This simple instrument-independent method is less expensive than the conventional instrumentdependent method and can be adopted by the blood banks of the developing countries where these viruses are highly endemic to possibly ensure the ac...

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