Epidemiologic and clinical features of patients with COVID-19 in Brazil

ABSTRACT Objective This study describes epidemiological and clinical features of patients with confirmed infection by SARS-CoV-2 diagnosed and treated at Hospital Israelita Albert Einstein , which admitted the first patients with this condition in Brazil. Methods In this retrospective, single-center study, we included all laboratory confirmed COVID-19 cases at Hospital Israelita Albert Einstein , São Paulo, Brazil, from February until March 2020. Demographic, clinical, laboratory and radiological data were analyzed. Results A total of 510 patients with a confirmed diagnosis of COVID-19 were included in this study. Most patients were male (56.9%) with a mean age of 40 years. A history of a close contact with a positive/suspected case was reported by 61.1% of patients and 34.4% had a history of recent international travel. The most common symptoms upon presentation were fever (67.5%), nasal congestion (42.4%), cough (41.6%) and myalgia/arthralgia (36.3%). Chest computed tomography was performed in 78 (15.3%) patients, and 93.6% of those showed abnormal results. Hospitalization was required for 72 (14%) patients and 20 (27.8%) were admitted to the Intensive Care Unit. Regarding clinical treatment, the most often used medicines were intravenous antibiotics (84.7%), chloroquine (45.8%) and oseltamivir (31.9%). Invasive mechanical ventilation was required by 65% of Intensive Care Unit patients. The mean length of stay was 9 days for all patients (22 and 7 days for patients requiring or not intensive care, respectively). Only one patient (1.38%) died during follow-up. Conclusion These results may be relevant for Brazil and other countries with similar characteristics, which are starting to deal with this pandemic.

Given the rapid spread of the COVID-19, clinical and epidemiological data of several countries are being published on a daily basis. (7)(8)(9) However, no studies have been reported to date presenting the characteristics of COVID-19 patients diagnosed in Brazil.

❚ OBJECTIVE
To describe epidemiological and clinical features of patients with confirmed infection by SARS-CoV-2, diagnosed and treated at Hospital Israelita Albert Einstein, which admitted the first patients with this condition in Brazil.

❚ METHODS Study design and oversight
This was a retrospective, observational, single-center study, which included all consecutive patients with a confirmed diagnosis of COVID-19, at HIAE, between February 26, 2020 and March 25, 2020. The study was supported by an internal grant from HIAE and designed by the investigators. The study was approved by the Research Ethics Committee of the organization, protocol number 3.921.190, CAAE: 30047620.3.0000.0071, and the National Commission for Research Ethics.

Patients
The diagnosis of the COVID-19 disease was performed according to the WHO interim guidance. (10) A confirmed case of COVID-19 was defined as a positive result of real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. (11) All cases included in the current analysis had laboratory confirmation.

Data sources
The data were obtained from patients' electronic medical records (EMR), including inpatients and outpatients with laboratory-confirmed COVID-19. Data collected included demographic, clinical, laboratorial and radiological information, and was anonymized so that patients could not be identified.
Demographic characteristics included age, sex, tobacco smoking, weight and body mass index (BMI). Clinical information included medical, travel einstein (São Paulo). 2020;18:1-7 and exposure history, signs, symptoms, underlying comorbidities, continuous medication use and treatment measures (i.e., antiviral therapy, steroid therapy, respiratory support and kidney replacement therapy). Laboratory assessment consisted of complete blood count, assessment of renal and liver function, and measurements of electrolytes, D-dimer, procalcitonin, lactate dehydrogenase, C-reactive protein, and creatine kinase. Radiologic abnormality was defined based on the medical report documented in the EMR. Disease duration from onset of symptoms, hospital and Intensive Care Unit (ICU) length of stay (LOS) were also documented.

Statistical analysis
Continuous variables were expressed as means with standard deviations, medians, minimum and maximum values. Categorical variables were summarized as counts and percentages. No imputation was made for missing data. All statistics are deemed to be descriptive only, considering that the cohort of patients in our study was not derived from random selection. All analyses were performed using Microsoft Excel 2013.

Demographic and clinical characteristics
Between February 26 and March 25, 2020, a total of 769 patients were diagnosed with COVID-19 at HIAE. This study included 510 (66%) patients, for whom data regarding demographics, clinical symptoms, laboratory and imaging findings were available in the EMR. The remaining 259 patients had only used the hospital laboratory facilities, and were followed-up by physicians not working in our service network.
Patients' demographic and clinical characteristics are shown in table 1. A total of 34.4% had a recent international travel history and 5.7% had been at the same marriage celebration in Bahia, a state in the Northeast region of Brazil; 184 (61.1%) patients had a history of close contact either with a positive or suspected case of COVID-19. Most patients were male (56.9%) and the mean age was 40 years. Only 0.6% of patients were younger than 11 years old and 6.5% were older than 65 years.
Fever was present in only 15.6% of patients upon admission, but 67.5% had a reported history of fever, followed by nasal congestion (42.4%), cough (41.6%)  Table 2 demonstrates the radiologic and laboratory findings upon admission. Only 7.3% of patients were initially evaluated with chest radiographs, whereas 15.3% were submitted to computed tomography (CT). Of the radiographs performed, 24.3% had some abnormality, while 93.6% of CT scans showed abnormal results. The most common patterns on chest CT were ground-glass opacity (84.6%) and bilateral patchy shadowing (79.5%).  Upon admission, lymphocytopenia was identified in 76.3% of patients, thrombocytopenia in 25.9%, and leukopenia in 21.5%. Most patients had elevated levels of both C-reactive protein and lactate dehydrogenase. Less common findings were elevated levels of D-dimer, aspartate aminotransferase and alanine aminotransferase. The hospitalized group had more patients with higher levels of C-reactive protein, procalcitonin and lactate dehydrogenase. The other results do not show any major difference between groups. A viral panel was collected in 146 (29%) patients, and it was positive for rhinovirus in nine cases, influenza B in two cases, and influenza A, in one case.

Treatment and complications
As shown in table 3, 72 (14%) patients had been hospitalized at HIAE by the time of the analysis. Among einstein (São Paulo). 2020;18:1-7 those, 20 patients (27.8%) required intensive care during their hospital stay; in that, 12 were referred from the emergency room to the ICU, and eight presented worsening of the clinical condition at inpatients units and were transferred to the ICU. The majority of patients received intravenous antibiotic therapy (84.7%), 45.8% received chloroquine and 31.9% oseltamivir. Oxygen therapy was necessary in 44.4% of hospitalized patients; 23.6% required mechanical ventilation (18.1% invasive and 5.6% non-invasive) and extracorporeal membrane oxygenation (ECMO) was used in only one case. Considering patients admitted to the ICU, invasive mechanical ventilation was required by 65% of them. During hospital admission, most patients were diagnosed with pneumonia (58.3%), followed by acute kidney injury (9.7%) and ARDS (8.3%). The mean LOS was 9 days; considering only patients requiring intensive care, the mean ICU LOS was 15.25 days, and the mean total LOS was 22 days, whereas for patients not admitted to the ICU, the mean LOS was 7 days. Only one patient died in this series, that is, 1.38% mortality rate.

❚ DISCUSSION
It took 3 months from the first diagnosed case of COVID-19 in China until diagnosis of patient zero in Brazil, on February 26, 2020, at HIAE. During 16 days after the first diagnosis, all cases had a history of recent international travels. On March 11, 2020, the first case of local transmission was confirmed, also at HIAE. A relevant proportion of all patients with confirmed COVID-19 infection had been diagnosed at HIAE by the time of the analysis.
The patients in our series had a mean age of 39.9 years and were mostly male (56.9%). The studies describing demographic characteristics in the infected general population showed a median age of 47 years, (7,12) and the proportion of males was 58.1% in the Chinese report (7) and 50% in the Singapore report. (12) The respiratory symptoms were similar to those of patients described in reports from China, United States and Europe. (7,9,13) However, the mean days of symptoms was far lower in our series (2.8 days versus 13 days in Singapore, (12) 7 days in the United States (13) and 7 days in China. (3) Although fever was reported by the majority of patients, it was only present in 15.6% of patients at the initial assessment at hospital, suggesting not only it might not be considered to determine severity of illness, but also that diagnostic algorithms using fever for testing may mask the total number of cases and delay diagnosis. The prevalence of chronic diseases was far higher in the hospitalized group (50%) as compared to non-hospitalized group (15.2%). This prevalence was even higher in the subgroup admitted to the ICU (80%).
The mean age of hospitalized patients was higher than non-hospitalized patients (51.8 versus 38.6 years) and the required hospitalization increased with age (7.8% for patients aged 12 to 49 years, 33.8% for 50 to 64 years, and 45.5% for patients older than 65 years). In this Brazilian case series, hospitalization was required for 72 (14.1%) patients, and 20 of them demanded critical care, accounting for 27.8% of total admissions, a number far greater than the Chinese series, in which only 5% required ICU. (7) The majority of patients were admitted to the ICU because of acute hypoxemic respiratory failure that required ventilatory support. Invasive mechanical ventilation was needed in 65% of ICU patients (18.1% of total hospitalizations), whereas 20% were managed with non-invasive mechanical ventilation. The necessity of invasive mechanical ventilation was similar to an ICU series reported from the United States (75% of Washington), (13) lower than that reported in an Italian publication (88% of Lombardy), (9) but higher than the Chinese reports (47%, 42% and 30% of Wuhan; half of these treated with extracorporeal membrane oxygenation). (3,14,15) Considering the use of non-invasive ventilation, the rate was again similar to that reported in Washington (19%) (12) and lower than the rates in China (42%, 56% and 62% of Wuhan, including patients receiving high-flow nasal cannula). (3,14,15) A total of three patients (15% of patients admitted to the ICU) developed acute kidney injury and required continuous renal replacement therapy. Among those, only one patient had chronic kidney disease. The prevalence of chronic kidney disease was 2.9% among hospitalized patients in the Chinese report, (14) and 21% among patients admitted to the ICU in the series from the United States (21%). (13) This study has important limitations. First, part of the cases had incomplete information documented in the medical records, and patient clinical history documentation was not homogeneous among all patients. This is a common limitation in retrospective observational studies, taking into account that data generation was clinically driven and not in systematic fashion. Second, since many patients remained at the hospital and the outcomes were unknown at the time of data collection, we censored the data regarding their clinical outcomes as of the time of the analysis. Third, only patients hospitalized at HIAE were included in the hospitalization group, and there is no documentation of hospital admissions outside of our service network. Finally, this study only included patients attended as outpatients or inpatients at HIAE; therefore, asymptomatic and mild cases who did not seek medical care were not considered. Hence, our study cohort may represent more severe COVID-19 cases.

❚ CONCLUSION
To date, there is no study in Brazil reporting the characteristics of patients diagnosed with COVID-19. Brazil is the country in the south hemisphere with the highest number of confirmed cases this disease and Hospital Israelita Albert Einstein is the center where the first patient was diagnosed, with a representative sample of all confirmed COVID-19 cases in the country. The results presented in this study may be relevant for Brazil and other countries with similar characteristics, which are starting to deal with this pandemic.