ABSTRACT
BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.
Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Antibodies, Viral , Betacoronavirus , COVID-19/therapy , Humans , Immunization, Passive , Immunoglobulin A , Immunoglobulin G/therapeutic use , SARS-CoV-2 , Treatment Outcome , COVID-19 SerotherapyABSTRACT
Objetivo: determinar la utilidad predictiva de la escala rápida de emergencias (REMS) en términos de mortalidad intrahospitalaria y estancia de pacientes adultos sean quirúrgicos o no que ingresan al servicio de urgencias del Hospital de San José de Bogotá. Método: estudio analítico, retrospectivo de pacientes que ingresaron a urgencias de un hospital de cuarto nivel de Bogotá, Colombia, entre septiembre 2016 y febrero 2017. Resultados: se incluyeron 1080 pacientes aleatoriamente con una frecuencia de muerte intrahospitalaria de 10.19% (n: 110), mediana de edad en los fallecidos de 73 años vs 55 años en los no fallecidos. La mediana calculada del puntaje de la escala REMS fue significativamente mayor en el grupo con de muerte intrahospitalaria 7 (5-10) que en los que no fallecieron 3 (0-3). Según el modelo de regresión logística las variables más relacionadas con muerte intrahospitalaria fueron: días de estancia intrahospitalaria (OR: 1.08 IC 95% 1.04-1.12), escala REMS (OR: 1.5 IC 95% 1.34 -1.7), inmunocompromiso (OR: 6.27 IC 95% 2.12-18.5) y patología oncológica (OR 12 IC 95% 6.25-26.6). El punto de corte asociado con mortalidad fue de 6 para la escala, teniendo en cuenta las otras variables que impactaron en la mortalidad se establece un OR de 4.3 (IC 95% 2.3 - 8). El poder discriminativo de la prueba da una AUC de 0.97 considerado bueno. Conclusiones: en nuestra población la escala REMS fue un buen predictor de mortalidad intrahospitalaria en urgencias por condición quirúrgica o no, considerándola como buena herramienta para la toma de decisiones clínicas, derivación y usos de recursos. No es posible establecer esta relación en condición traumática debido al tamaño de la muestra. Teniendo en cuenta el análisis de otras variables es posible establecer una nueva escala en la cual se incluya el REMS y variables asociadas estadísticamente significativas.
Objective: to test the Rapid Emergency Medicine Score (REMS) utility as a predictor in terms of in-hospital mortality and hospital stay in adult surgical and non-surgical patients admitted to the emergency department (ED) of Hospital de San José in Bogotá. Method: this was an analytic retrospective study including patients admitted to a fourth level hospital in Bogotá, Colombia ED, between September 2016 and February 2017. Results: 1080 patients were randomly included obtaining an in-hospital mortality rate of 10.19% (n: 110), median age of nonsurvivors 73 years vs 55 years of survivors. The estimated median REMS was significantly higher in the in-hospital nonsurvivors group 7 (5-10) than that in the survivors group 3 (0-3). A logistic regression analysis demonstrated variables most related with in-hospital death were: days of hospital stay (OR: 1.08 95% CI 1.04 to 1.12), REMS (OR: 1.5 95% CI 1.34 to 1.7), immunocompromised state (OR: 6.27 95% CI 2.12 to 18.5) and oncologic pathology (OR 12 95% 6.25 to 26.6). The mortality cut off point for the scale was 6. An OR of 4.3 (95% CI 2.3 to 8) was obtained considering the other variables that impacted mortality. The discriminatory power of the area under the curve (AUC) value of 0.97 was considered good. Conclusions: in our population REMS was a good predictor tool of in-hospital mortality in surgical and non-surgical patients admitted to the ED, and was considered a good tool for clinical decision making, classification and resource use. This score could not be employed to discriminate trauma patients due to the sample size. Considering the analysis of other variables, a new scale including REMS may be developed including associated statistically significant variables.