Síndrome do desconforto respiratório agudo associada à COVID-19 tratada com DEXametasona (CoDEX): delineamento e justificativa de um estudo randomizado / COVID-19-associated ARDS treated with DEXamethasone (CoDEX): study design and rationale for a randomized trial

RESUMO Objetivo: A infecção causada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) disseminou-se por todo o mundo e foi categorizada como pandemia. As manifestações mais comuns da infecção pelo SARS-CoV-2 (doença pelo coronavírus 2019 - COVID-19) se referem a uma pneumonia viral com graus variáveis de comprometimento respiratório e até 40% dos pacientes hospitalizados, que podem desenvolver uma síndrome do desconforto respiratório agudo. Diferentes ensaios clínicos avaliaram o papel dos corticosteroides na síndrome do desconforto respiratório agudo não relacionada com COVID-19, obtendo resultados conflitantes. Delineamos o presente estudo para avaliar a eficácia da administração endovenosa precoce de dexametasona no número de dias vivo e sem ventilação mecânica nos 28 dias após a randomização, em pacientes adultos com quadro moderado ou grave de síndrome do desconforto respiratório agudo causada por COVID-19 provável ou confirmada. Métodos: Este é um ensaio pragmático, prospectivo, randomizado, estratificado, multicêntrico, aberto e controlado que incluirá 350 pacientes com quadro inicial (menos de 48 horas antes da randomização) de síndrome do desconforto respiratório agudo moderada ou grave, definida segundo os critérios de Berlim, causada por COVID-19. Os pacientes elegíveis serão alocados de forma aleatória para tratamento padrão mais dexametasona (Grupo Intervenção) ou tratamento padrão sem dexametasona (Grupo Controle). Os pacientes no Grupo Intervenção receberão dexametasona 20mg por via endovenosa uma vez ao dia, por 5 dias, e, a seguir, dexametasona por via endovenosa 10mg ao dia por mais 5 dias, ou até receber alta da unidade de terapia intensiva, o que ocorrer antes. O desfecho primário será o número de dias livres de ventilação mecânica nos 28 dias após a randomização, definido como o número de dias vivo e livres de ventilação mecânica invasiva. Os desfechos secundários serão a taxa de mortalidade por todas as causas no dia 28, a condição clínica no dia 15 avaliada com utilização de uma escala ordinal de seis níveis, a duração da ventilação mecânica desde a randomização até o dia 28, a avaliação com o Sequential Organ Failure Assessment Score após 48 horas, 72 horas e 7 dias, e o número de dias fora da unidade de terapia intensiva nos 28 dias após a randomização.

Abstract Objective: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. Methods: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.

[Cytomegalovirus: congenital infection and clinical presentation in infants with respiratory distress syndrome]. / Citomegalovirus: infección congénita y presentacion clínica en recién nacidos con síndrome de dificultad respiratoria.

BACKGROUND: Respiratory distress syndrome (RDS) is a multifactorial and common disease that varies from 15 to 50 % in the newborn, causing 50 % of mortality. The RDS may be associated with bacterial and viral infections, and one of the most common viral agents is the cytomegalovirus (CMV). In the neonatal period the virus incidence goes from 0.4 to 2.5 % with a seroprevalence of 50 to 75 %; the incidence of infection in newborn with RDS is unknown. The objective was to determine the frequency of CMV infection in neonates with RDS and identify the risk factors associated with infection. METHODS: The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression.The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression. RESULTS: The frequency of CMV infection in 197 infants with RDS was 8.6 % (95 % CI, 4.7-12.5). The significant variables in newborn were: neutropenia (p = 0.012), thrombocytopenia (p = 0.021), mottled skin (p = 0.03), and the maternal significant variable was cervicovaginitis (p = 0.05). CONCLUSIONS: We reported for the first time the highest frecuency of CMV infection in newborns with RDS and the association of various risk factors with CMV infection.

Introducción: el síndrome de dificultad respiratoria (SDR) es una enfermedad común multifactorial que varía del 15 al 50 % en el recién nacido (RN), y la mortalidad es de 50 %. Puede estar asociado a infecciones bacterianas y virales, una de las más frecuentes: el citomegalovirus (CMV). En el periodo neonatal la incidencia de infección por CMV es de 0.4 a 2.5 % y la seroprevalencia de 50 a 75 %; se desconoce la incidencia de infección en los RN. El objetivo fue determinar la frecuencia de infección por CMV en recién nacidos con SDR e identificar factores de riesgo asociados a infección. Métodos: el DNA-CMV fue identificado en plasma por reacción en cadena de la polimerasa (PCR) cuantitativa, y las variables maternas y neonatales que definieron el cuadro clínico fueron analizadas por regresión logística. Resultados: la frecuencia de infección por CMV en 197 RN con SDR fue de 8.6 % (IC 95 % 4.7-12.5). Las variables significativas en los RN fueron: neutropenia (p = 0.012), trombocitopenia (p = 0.021), piel marmórea (p = 0.03) y la variable materna significativa fue cervicovaginitis (p = 0.05). Conclusiones: se reporta por primera vez la frecuencia más alta de infección por CMV en RN con SDR y la asociación de varios factores de riesgo con la infección por CMV.

[Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97]. / Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97.

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro Kourí Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in children's under 1 year of age.

Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97 / Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro KourY Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in childrens under 1 year of age.(AU)