ABSTRACT Objective To evaluate deaths, hospitalizations, and persistence of symptoms in patients with COVID-19 after infection in an outpatient setting during the first COVID-19 wave in Brazil. Methods This prospective cohort was between April 2020 and February 2021. Hospitalized or non-hospitalized COVID-19 patients until five days after symptom onset were included. The outcomes measured were incidence of death, hospitalization, and persistence of more than two symptoms 60 days after discharge. Results Out of 1,198 patients enrolled in the study, 66.7% were hospitalized. A total of 289 patients died (1 [0.3%] non-hospitalized and 288 [36%] hospitalized). At 60 days, patients non-hospitalized during admission had more persistent symptoms (16.2%) compared to hospitalized (37.1%). The COVID-19 severity variables associated with the persistence of two or more symptoms were increased age (OR= 1.03; p=0.015), respiratory rate at hospital admission (OR= 1.11; p=0.005), length of hospital stay of more than 60 days (OR= 12.24; p=0.026), and need for intensive care unit admission (OR= 2.04; p=0.038). Conclusion COVID-19 survivors who were older, tachypneic at admission, had a hospital length of stay >60 days, and were admitted to the intensive care unit had more persistent symptoms than patients who did not require hospitalization in the early COVID-19 waves. ClinicalTrials.gov Identifier: NCT04479488. deaths hospitalizations COVID19 COVID 19 COVID-1 Brazil 202 2021 nonhospitalized non included death 6 discharge 1198 1 198 1,19 study 667 66 7 66.7 28 ( 0.3% 03 0 3 [0.3% 36% 36 [36% . hospitalized) 16.2% 162 16 2 (16.2% 37.1%. 371 37.1% 37 (37.1%) OR= OR (OR 1.03 103 p=0.015, p0015 p p=0.015 , 015 p=0.015) 1.11 111 11 p=0.005, p0005 p=0.005 005 p=0.005) 12.24 1224 12 24 p=0.026, p0026 p=0.026 026 p=0.026) 2.04 204 04 p=0.038. p0038 p=0.038 038 p=0.038) older >6 waves ClinicalTrialsgov ClinicalTrials gov Identifier NCT04479488 NCT COVID1 COVID- 20 119 1,1 66. 0.3 [0.3 [36 16.2 (16.2 37.1 (37.1% 1.0 10 p001 p=0.01 01 1.1 p000 p=0.00 00 12.2 122 p002 p=0.02 02 2.0 p003 p=0.03 > NCT0447948 1, 0. [0. [3 16. (16. 37. (37.1 1. p00 p=0.0 12. 2. NCT044794 [0 [ (16 (37. p0 p=0. NCT04479 (37 p=0 NCT0447 (3 p= NCT044 NCT04 NCT0

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098 Antecedentes sódioglicose sódio glicose renais investigados Métodos investigador multicêntrico randomizado aberto 50 11 1 1: mg hospitalar Conclusão críticos ClincalTrials.gov ClincalTrialsgov ClincalTrials gov NCT NCT0555809 5 NCT055580 NCT05558 NCT0555 NCT055 NCT05 NCT0

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098 Background rates Sodiumglucose Sodium glucose cotransporter2 cotransporter 2 cotransporter- outcomes sodiumglucose sodium investigated Methods investigatorinitiated, investigatorinitiated investigator initiated, initiated investigator-initiated multicenter openlabel open label 50 11 1 1: mg alone therapy stay Conclusion ClinicalTrialsgov ClinicalTrials gov registry NCT NCT0555809 5 NCT055580 NCT05558 NCT0555 NCT055 NCT05 NCT0