However, only 2 of 36 SAEs were judged mainly because definitely related to the convalescent plasma transfusion from the treating physician. the treating physician. The 7-day time mortality rate was 14.9%. Summary Given the fatal nature of COVID-19 and the large human population of critically ill individuals included in these analyses, the mortality rate does not appear excessive. These early signals suggest that transfusion of convalescent plasma is definitely safe in hospitalized individuals with COVID-19. TRIAL Sign up ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT04338360″,”term_id”:”NCT04338360″NCT04338360. FUNDING Mayo Medical center, Biomedical Advanced Study and Development Expert (75A50120C00096), National Center for Improving Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Executive Study Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease SHP2 IN-1 (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Account, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc. = 3; probably, = 1; definitely, = 0) to the transfusion of COVID-19 convalescent plasma. There were 21 nondeath SAEs reported, with 7 reports of transfusion-associated circulatory overload (TACO), 11 reports of transfusion-related acute lung injury (TRALI), and 3 reports of severe sensitive transfusion reaction. All incidences of TACO and TRALI were judged as related (probably, = 9; probably, = 7; definitely, = 2) to the transfusion of COVID-19 convalescent plasma. The SAEs and their attributions are summarized in Table 2. Table 2 Serious adverse event characteristics (= 5,000) Open in a separate window On the first 7 days after the convalescent plasma transfusion, a total of 602 mortalities were observed. SHP2 IN-1 The overall 7-day time mortality rate was estimated to be 14.9% (95% CI, 13.8%, 16.0%) using the product limit estimator, an estimate that was numerically higher than the crude estimate of 12.0% at day time 7. Of the 3316 individuals admitted to the ICU, 456 mortalities were observed (16.7%, 95% CI, 15.3%, 18.1%). Of the 1682 hospitalized individuals not admitted to the ICU, 146 mortalities were observed (11.2%, 95% SHP2 IN-1 CI, 9.5%, 12.9%). Conversation Safety summary. With this initial statement of 5000 hospitalized individuals in the US with severe or life-threatening COVID-19, or who have been judged by a health care provider to be at high risk of progressing to severe or life-threatening COVID-19, the overall rate of recurrence of SAEs within 4 hours following a transfusion of COVID-19 convalescent plasma was less than 1% (= 36) and the 7-day time mortality DLL3 rate was 14.9%. Although 70% of these SAEs were deemed to be related to plasma transfusion by treating physicians, most of the SAEs (56%) were judged as probably related, suggesting uncertainty about the part of the transfusion per se in the adverse reaction. Additionally, the pace of SAEs definitely related to transfusion was objectively low (= 2, 0.1% of all transfusions). Although this study was not designed to evaluate effectiveness of convalescent plasma, we notice with optimism the relatively low mortality in treated individuals. The case fatality rate of COVID-19 has been reported to be approximately 4% among all individuals diagnosed with COVID-19 (2). However, the case fatality rate among hospitalized individuals is much higher and more variable at approximately 10%C20% (3, 5), particularly among individuals admitted to the ICU (4). Therefore, the 7-day time mortality rate of 14.9% reported here is not alarming, particularly because some of these plasma transfusions may be characterized as attempts at rescue or salvage therapy in patients admitted to the ICU with multiorgan failure, sepsis, and significant comorbidities. Despite these early and motivating safety signals, there are several risks of COVID-19 convalescent plasma transfusion in critically ill individuals that warrant attention SHP2 IN-1 in this initial assessment of security (12, 13). TRALI and TACO. The highest risk of mortality following plasma transfusion is likely due to sequelae pulmonary complications (14), and this risk SHP2 IN-1 is probably exacerbated from the underlying respiratory distress associated with COVID-19. TRALI and TACO are the 2 leading causes of transfusion-related mortality, and they are often hard to distinguish. These conditions have been emphasized in the plasma transfusion literature, but making an unequivocal dedication of plasma-related toxicity in critically ill individuals is definitely difficult in the face of ongoing conditions that resemble transfusion SAEs. As a result, it is likely that some of the reported SAEs represent natural progression of the ongoing pathological processes. The most common adverse event associated with plasma transfusion in critically ill individuals is definitely TACO, which results.