Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

Natalidad y riesgo reproductivo en adolescentes de Chile, 1990­1999 / Birth rates and reproductive risk in adolescents in Chile, 1990­1999

OBJETIVOS: Evaluar en madres adolescentes chilenas menores de 15 años y de 15 a 19 años las tendencias de la natalidad y del riesgo reproductivo en el período de 1990­1999. MÉTODOS: Sobre la base de datos extraídos de los Anuarios de demografía publicados por el Instituto Nacional de Estadísticas de Chile para 1990­1999, se calcularon las tendencias mostradas por el número de nacidos vivos y las tasas de mortalidad materna, fetal tardía, neonatal e infantil entre madres adolescentes menores de 15 años y de 15 a 19 años de edad. Se calculó el riesgo (razón de posibilidades, RP) de ambos grupos en comparación con el de mujeres de 20 a 34 años de edad. La comparación entre grupos se efectuó mediante la prueba de Fisher o de ji2, según el caso, y el análisis de tendencias en el período estudiado se realizó mediante la correlación de Pearson con un nivel alfa de 0,05. RESULTADOS: En el período estudiado, las tasas de mortalidad materna, fetal tardía, neonatal e infantil en madres adolescentes menores de 15 años fueron, respectivamente, de 41,9 (por 100 000 nacidos vivos [NV]), 5,1 (por 1 000 NV), 15,2 (por 1 000 NV) y 27,4 (por 1 000 NV); en adolescentes de 15 a 19 años, de 19,3, 4,1, 8,1 por 1 000 y 16,6, respectivamente, mientras que en adultas de 20 a 34 años dichas tasas fueron de 26,8, 5,0, 6,7 y 12,1, respectivamente. En las adolescentes menores de 15 años el mayor riesgo de muerte materna (RP = 1,56; IC95 por ciento: 0,50 a 4,31; P = 0,372) y de muerte fetal (RP = 1,02; IC95 por ciento: 0,76 a 1,36; P = 0,890) no fue estadísticamente significativo; en cambio, sí se detectó un riesgo significativamente mayor de muerte neonatal (RP = 2,27; IC95 por ciento: 1,92 a 2,68; P <0,0001) y el de muerte infantil (RP = 2,39; IC95 por ciento: 2,04 a 2,62; P <0,0001). Entre las madres adolescentes de 15 a 19 años, el riesgo de muerte materna (RP = 0,72; IC95 por ciento: 0,56 a 0,92; P <0,008) y el de muerte fetal (RP = 0,81; IC95 por ciento: 0,77 a 0,86; P <0,0001) fueron inferiores en grado significativo en comparación con los del grupo testigo, mientras que el riesgo de muerte neonatal (RP = 1,20; IC95 por ciento: 1,16 a 1,25; P <0,0001) y el de muerte infantil (RP = 1,38; IC95 por ciento: 1,35 a 1,42; P <0,0001) fueron significativamente superiores...

Objective. For Chilean teenage mothers under 15 years old and from 15 to 19 years old, to evaluate the trends in birth rates and reproductive risk for the period of 1990­1999. Methods. A database was constructed using data from the Demography Yearbook (Anuario de demografía) volumes published by Chile's National Institute of Statistics (Instituto Nacional de Estadísticas) for 1990­1999. From that database we calculated the trends in the number of live births and in the rates of maternal mortality, late fetal mortality, neonatal mortality, and infant mortality among the teenage mothers under 15 and from 15 to 19 years old. We calculated the risk odds ratio (OR) for both of those age groups in comparison with women from 20 to 34 years old. The groups were compared using Fisher's exact test or the chi-square test, and the analysis of trends in the period studied was carried out with Pearson's correlation, with an alpha level of 0.05. Results. In the period studied, for the teenage mothers under age 15, the respective rates for maternal mortality, late fetal mortality, neonatal mortality, and infant mortality were 41.9 per 100 000 live births, 5.1 per 1 000 live births, 15.2 per 1 000 live births, and 27.4 per 1 000 live births. For the adolescents from 15 to 19 years, the corresponding rates were 19.3, 4.1, 8.1, and 16.6; for the women 20­34 years old, they were 26.8, 5.0, 6.7, and 12.1. The adolescents under 15 had higher risks of maternal mortality (OR = 1.56; 95% confidence interval (CI): 0.50 to 4.31; P = 0.372) and of fetal mortality (OR = 1.02; 95% CI: 0.76 to 1.36; P = 0.890), but those differences were not statistically significant. However, the younger adolescents did have significantly higher risks of neonatal mortality (OR = 2.27; 95% CI: 1.92­2.68; P < 0.0001) and of infant mortality (OR = 2.39; 95% CI: 2.04 to 2.62; P < 0.0001). In comparison to the women 20­34 years old, the teenage mothers from 15 to 19 years old had significantly lower risks of maternal mortality (OR = 0.72; 95% CI: 0.56 to 0.92; P < 0.008) and of fetal mortality (OR = 0.81; 95% CI: 0.77 to 0.86; P < 0.0001) but significantly higher risks of neonatal mortality (OR = 1.20; 95% CI: 1.16 to 1.25; P < 0.0001) and of infant mortality (OR = 1.38; 95% CI: 1.35 to 1.42; P < 0.0001). Among both the older teenage mothers and the mothers 20­34 years old there was a significant downward trend in maternal, fetal, neonatal, and infant mortality rates in the period studied; in the younger adolescents only neonatal mortality and infant mortality declined significantly. There was a rising trend in the number of live births among the two groups of teenage mothers, but that trend was statistically significant only for the mothers under 15; among mothers 20­34 years old there was a statistically significant downward trend. Conclusions. In the period studied, the Chilean teenage mothers faced greater reproductive risk than did the women 20­34 years old. The number of live births among teenage mothers tended to rise during the 1990­1999 period, but the change was significant only for the mothers under age 15. These results point to the need to develop programs that improve both sex education and birth control practices starting in early adolescence