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.

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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

Background/Objective: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and marked dysplastic features. Establishing MDS diagnosis is difficult due to nonspecific clinical presentation and imprecise morphological criteria. In anticipation to improve the diagnostic approach in this field, we aimed to characterize the clinical and morphological features of patients presented with cytopenias with a special focus on MDS. Methods: We comprehensively reviewed all medical record of patients who were referred to the hematology laboratory at KFSH-RC, Riyadh, Saudi Arabia, between January 2009 and March 2016 for evaluation of bone marrow aspirates and trephine biopsies due to severe and persistent cytopenia(s) to rule out MDS. Results: A total of 183 patients, 155 adult and 28 pediatric, were identified. In the adult group, MDS was diagnosed in 82 (52.9%) patients, with a male-to-female (M:F) ratio of 1.6:1 and mean age at diagnosis of 50 years. According to the World Health Organization (WHO) 2017 criteria, MDS subtypes were as follows: MDS with single lineage dysplasia (SLD, 5%), MDS with ring sideroblasts and SLD (MDS-RS-SLD 7%), MDS with multilineage dysplasia (MDS-MLD 21%), MDS with deletion of chromosome 5q (MDS del(5q), 2%), MDS unclassifiable (MDS-U7%), hypoplastic MDS (h-MDS 4%), MDS with excess blasts-1 (MDS-EB1, 20%), MDS with excess blasts-2 (MDS- EB2, 28%), and therapy-related MDS (6%). Laboratory and morphological features were described. In both groups, cytogenetic abnormalities were classified according to the Revised International Prognostic Scoring System cytogenetic risk groups. In adults, the dominating cytogenetic abnormalities were monosomy 5 and monosomy 7 seen in 20.7% and 24.4% of patients, respectively. Peripheral cytopenia not due to MDS was diagnosed in 54 (34.8%) patients, with a mean age of 43 years and M:F ratio of 1:1. The cause of these cytopenias were as follows: bone marrow failure (BMF, 22%), peripheral destruction (20%), drug induced (20%), anemia of chronic disease (16%), B12 deficiency (7%), infection (7%), paroxysmal nocturnal hemoglobinuria (4%), idiopathic cytopenia of undetermined significance (2%), and idiopathic dysplasia of undetermined significance (2%). A definite diagnosis of MDS was not possible in 19 patients due to insufficient clinical data. In the pediatric group, MDS was diagnosed in 14/28 (50%) patients, with M:F ratio of 1.8:1 and mean age at diagnosis of 4 years. MDS subtypes (WHO 2017) in 14 patients were as follows: refractory cytopenia of childhood (RCC, 42.8%), MDS-EB1 (42.8%), and MDS-EB2 (14.2%). Laboratory and morphological features were described. The prevalent cytogenetic abnormality was monosomy 7 in six/14 (42.8%) patients. Cytopenias due to other causes were diagnosed in eight/28 patients (28.5%), with a mean age of 6.5 years and M:F ratio of 1.6:1. The causes of non-MDS related cytopenia were: congenital BMF (4 patients), peripheral destruction (2 patients), immune deficiency (1 patient), and viral infection (1 patient). A definite diagnosis of MDS could not be made in six/28 (21.4%) patients. Conclusion: MDS is the cause of cytopenia in a significant number of patients referred for evaluation of cytopenias, appears at younger age, and tends to be more aggressive than that reported in international studies. Anemia, dysplastic neutrophils in the peripheral blood, and dysplastic megakaryocytes in the bone marrow trephine biopsy are the most reliable features in distinguishing MDS from other alternative diagnoses.