key: cord-0699481-whpdw25y authors: Marcolino, Milena S.; Ziegelmann, Patricia K.; Souza-Silva, Maira V.R.; do Nascimento, Israel J. Borges; Oliveira, Luana M.; Monteiro, Luanna S.; Sales, Thaís L.S.; Ruschel, Karen B.; Martins, Karina P.M.P.; Etges, Ana Paula B.S.; Molina, Israel; Polanczyk, Carisi A. title: Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: results from the Brazilian COVID-19 Registry date: 2021-01-12 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.01.019 sha: 5778d93f13fe999a276f7bcfabdf7e542fa60c89 doc_id: 699481 cord_uid: whpdw25y Objectives To describe clinical characteristics, laboratory and imaging findings, as well as in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. Methods Cohort study of laboratory-confirmed COVID-19 patients hospitalized from March to September 2020 at 25 hospitals. Study data were collected from medical records using Research Electronic Data Capture (REDCap) tools. Multivariate Poisson regression model was used to assess risk factors for in-hospital mortality. Results Of 2054 patients (52.6% male, median age 58 years old), in-hospital mortality was 22.0%, and 47.6% among those treated in the ICU. Hypertension (52.9%), diabetes (29.2%) and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation and 12.1% kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1% and acute heart failure in 3.6%. Age ≥65 years-old, chronic kidney disease, hypertension, C-reactive protein ≥100 mg/dL, platelet count <100 × 109/L, oxygen saturation <90%, supplementary oxygen requirement and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. Conclusions This study provides characteristics and in-hospital outcomes of consecutively hospitalized patients with confirmed COVID-19 in Brazil. Easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients. is not possible to predict whether the clinical characteristics of patients who are hospitalized due to COVID-19 and the determinants of severe disease in Brazil are the same observed in China and Europe. (Bambra et al., 2020) Knowing the characteristics of hospitalized COVID-19 patients, the need for resources and their clinical outcomes is of utmost importance to support clinical decision making and public health management. We therefore performed a multicenter study aimed to characterise clinical, laboratory and imaging features, as well as outcomes of patients with COVID-19 admitted to Brazilian hospitals. Additionally, we explored risk factors associated with in-hospital mortality. The Brazilian COVID- 19 For the purpose of the present study, patients who had completed hospitalization and were in the database by September 19, 2020 were included. Patients who were transferred to another hospital within the first three days after being admitted were only counted if data from the hospital they wound up at was available, otherwise they were excluded ( Figure 1 ). Sample size was not calculated, as all patients who met the inclusion criteria were included. Medical records were reviewed to collect data on patients' characteristics, including age, sex and occupation (whether the patient was a healthcare professional); pre-existing comorbid medical conditions and home medications; COVID-19 associated symptoms at hospital presentation; clinical assessment at admission, third and fifth admission days; laboratory, imaging, electrocardiographic and echocardiographic data; inpatient medications, treatment and outcomes. The data collection instrument was designed considering COVID-19 guidelines from the World Health Organization and the Brazilian Ministry of Health. Definitions can be assessed in Supplementary Material 1. Descriptive analyses were used to summarize all variables, stratified by in-hospital survival status. The Shapiro-Wilk normality test was performed to check for the normal distribution of continuous variables. As all variables had non-normal distribution, they were summarized using medians and interquartile ranges (IQR). Categorical variables were summarized with counts and percentages. The study population was divided into ten age groups Table 1 and Supplementary Table 1. In-hospital mortality was 22.0% (95% confidence interval [CI] 20.2-23.9%), and the median time between admission and death was 12 days (IQR: 6-18). Figure 2 shows admissions and mortality over time. The apparent higher mortality in September is due to the reduced number of cases who were hospitalized and in the database at that time. In-hospital mortality and hospital length of stay for those who died or were discharged alive by 10-year age intervals and sex are presented in Supplementary Table 2 . Overall, there was no difference in in-hospital mortality between men and women (22.9% vs. 21.1%, p=0.322), but it was higher for men compared with women at every 10-year age interval up to 69 years old. For the 84 healthcare workers included, mortality was 9.5%. The median age was 46 [IQR 37-55] years old, the median number of comorbidities was 1 (IQR 0-2) and the median time from symptom onset to presentation 7 (IQR 5-10) days. When adjusted for age and sex, being a healthcare worker was not significant associated with reduced mortality risk (RR=0.60; 95%CI 0.30-1.10). Overall, 79.8% patients had at least one comorbidity. Mortality among those with at least one comorbidity was higher compared with those with none (25.5% vs 8.6%, p<0.001), J o u r n a l P r e -p r o o f and the median number of comorbidities was higher among those who died when compared to those discharged alive ( Cough (65.1%), dyspnea (61.6%) and fever (59.0%) were the most common symptoms at hospital presentation. Dyspnea and neurological impairment at hospital admission were more common among patients who died (Table 2) . Seventy-three (3.6%) patients who were admitted for other reasons later developed COVID-19 during their stay. Excluding these patients, the median time from symptom onset to presentation was 6 (IQR 3-9) days. The median duration of symptoms prior to the hospitalization was shorter for patients who died compared to those who survived (5 [IQR [2] [3] [4] [5] [6] [7] [8] vs. 7 [IQR 4-10], respectively; p<0.001). Laboratory and imaging findings are presented in Table 3 and Supplementary Table 3 . Patients who died from COVID-19 infection had higher mean white blood cell counts, higher absolute neutrophil counts, lower lymphocyte counts, higher creatinine and increased inflammatory response with significantly elevated C-reactive protein (CRP) levels. Chest X-rays were done in 1219 patients (59.3%) at admission and it was abnormal in 98.7% the most common pattern being a reticular interstitial thickening in 53.0% and ground Public or mixed hospitals had higher mortality rates compared with private ones (24.7% vs. 26.2% vs. 10.8%, p<0.001), and they were associated with higher mortality risk at univariate analysis. Those differences could be explained by the coexistence of other variables (age, comorbidities; delayed access to healthcare, different criteria for hospitalization). In fact, the average number of comorbidities was lower in patients from private hospitals (1 [IQR 0-2]) than the ones from public and mixed hospitals (2 [IQR 1-3] for both, p<0.001). Once eliminating the collinearity effect of those variables, no effect over prognosis was observed among the types of hospital. This factor is especially relevant in the Brazilian Healthcare System. Users of public or mixed hospitals could have different socio-economical profiles. A recent study conducted using data from the Brazilian Surveillance System also showed increased mortality in regions with a lower development index level, as well as among black populations, representing a regional and ethnicity effect, respectively. (Baqui et al., 2020) Additionally, low income has been associated with higher incidence of comorbidities such as hypertension, cardiovascular disease, chronic kidney disease and obesity. (Singu et al., 2020) J o u r n a l P r e -p r o o f What could have been a pre-condition of poor prognosis might have been compensated by excellent care in the public health system. Although Brazil is a country with one of the highest COVID-19-related death tolls for healthcare workers, the large number refers more to the high absolute number of cases than to a high mortality itself. (Domínguez-Varela, 2020) Mortality among healthcare workers was lower than the overall patients in our study, which may be associated to younger age, lower prevalence of comorbidities and awareness to identify early signs of deterioration. The analysis of secondary outcomes confirms the growing body of evidence of the multi-systemic nature of COVID-19, affecting not only the respiratory system, but also the kidneys, cardiovascular and nervous systems. Acute kidney injury was seen in almost a third of patients, and in over 68% of those who died. This is a higher proportion than in previous Additionally, as it is based in a mandatory registration system, at patient admission to emergency departments the complete fulfillment of the notification form might be compromised due to the high demand (several incoming patients hourly), insufficient staffing with medical personnel and also the presence of severe cases, which requires more attention. Additionally, the data entry with free-text fields from multiple locations and professionals causes an inherent contrast on the use of medical terms and description, which also results in a heterogeneity of fulfilment. Therefore, the most complete and accurate medical history (including information about underlying diseases and a more detailed description of symptoms) is sometimes not possible to be achieved. (Nascimento et al., 2020) One of the main strengths of the study was the fact that it is a real-life database, which included comprehensive data of a large sample size of patients from 25 hospitals in different Brazilian regions, able to ensure diversity of the population studied. Data were obtained by detailed medical record review, with higher degree of detail than electronic abstraction of structured data elements. Data was submitted to periodic auditing to ensure data quality and the analysis provided a thorough assessment of various outcomes in hospitalized COVID-19 patients. The data may be useful to inform healthcare planning in preparation for the next phase of the pandemic. The next step would be to create and validate a prediction tool for in-hospital mortality based on the prediction model, to support frontline clinical decision making. The sponsors had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Data are available upon reasonable request. 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Total number of valid cases for each analysis is presented HR: heart rate, SBP: systolic blood pressure, RR: respiratory rate AMI: acute myocardial infarction, ECMO: extracorporeal membrane oxygenation, HF: heart failure, ICU: intensive care unit, RRT: renal replacement therapy.