ABSTRACT
ImportancePassive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. ObjectiveTo explore potential signals of efficacy of COVID-19 convalescent plasma. DesignOpen-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. SettingMulticenter, including 2,807 acute care facilities in the US and territories. ParticipantsAdult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. InterventionTransfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and MeasuresSeven and thirty-day mortality. ResultsThe 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. Conclusions and RelevanceThe relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. Trial RegistrationClinicalTrials.gov Identifier: NCT04338360 Key PointsO_ST_ABSQuestionC_ST_ABSDoes transfusion of human convalescent plasma reduce mortality among hospitalized COVID-19 patients? FindingsTransfusion of convalescent plasma with higher antibody levels to hospitalized COVID-19 patients significantly reduced mortality compared to transfusions with low antibody levels. Transfusions within three days of COVID-19 diagnosis yielded greater reductions in mortality. MeaningEmbedded in an Expanded Access Program providing access to COVID-19 convalescent plasma and designed to assess its safety, several signals consistent with efficacy of convalescent plasma in the treatment of hospitalized COVID-19 patients emerged.
ABSTRACT
BACKGROUND@#The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD.@*METHODS@#The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups.@*RESULTS@#The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups.@*CONCLUSIONS@#The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.
