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PLOS ONE logoLink to PLOS ONE
. 2021 Jan 7;16(1):e0244532. doi: 10.1371/journal.pone.0244532

Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study

Rodrigo A Brandão Neto 1,, Julio F Marchini 1,¶,*, Lucas O Marino 1, Julio C G Alencar 1, Felippe Lazar Neto 1, Sabrina Ribeiro 1, Fernando V Salvetti 1, Hassan Rahhal 1, Luz Marina Gomez Gomez 1, Caue G Bueno 1, Carine C Faria 1, Victor P da Cunha 1, Eduardo Padrão 1, Irineu T Velasco 1, Heraldo Possolo de Souza 2; Emergencia USP Covid group
Editor: Walter R Taylor3
PMCID: PMC7790269  PMID: 33411707

Abstract

Background

The first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients.

Methods

From 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others.

Results

From 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality

Conclusions

This was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies.

Trial registration

The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5.

Introduction

In December 2019, several cases of pneumonia of unknown aetiology were reported in Wuhan, Hubei, China [1]. A few weeks later, a novel enveloped betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [2] was identified as the etiologic agent, and the new disease was announced as coronavirus disease (COVID-19) [3]. Less than 6 months after its discovery, COVID-19 was responsible for more than 7 million cases and 400,000 deaths worldwide [4].

In Brazil, the first case of COVID-19 was diagnosed in February 2020, and the community transmission was established in March. In June, the World Health Organization (WHO) declared Brazil as the new epicentre of the disease, with more than 832,000 cases and 42,000 deaths [4].

São Paulo is the most developed and populous state in Brazil and is where the first COVID-19 cases were diagnosed in the country. Several temporary hospitals have been built following the surge of cases, and this service, the largest public hospital in the state, has been designated to provide medical care exclusively to patients with COVID-19.

In this study, we report our experience with these patients, all of whom were admitted owing to a confirmed or suggested diagnosis of COVID-19. Our objective is to report the characteristics of our patients, their clinical course during admission, their final outcome and finally to identify independent predictors of death. All of them had pneumonia of at least moderate severity, which has been considered as a defining characteristic of COVID-19 by the WHO [5], and they all required hospitalisation.

To our knowledge, this is the first report of a series of COVID-19 cases in the Southern Hemisphere. It is also noteworthy that, contrary to China, Europe, and the United States, the COVID-19 pandemic has affected Brazil during the warm weather. Comparing experiences among different countries and identifying changes in disease virulence and lethality over time may be vital for understanding and containing this pandemic.

Methods

Study design

From 14 March to 16 May 2020, all patients admitted to the Emergency Department (ED) of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were enrolled in this study. The hospital is a 1000-bed quaternary academic medical centre and is affiliated to the University of São Paulo in the city of São Paulo, Brazil. During this pandemic, the state government designated this hospital to be the reference centre for all moderate and severe cases of COVID-19. Our ED admitted the vast majority of patients from the city. Moreover, patients suggested of having COVID-19 who were received in other institutions were also transferred to our ED. From these patients, this study analysed those who met the following criteria:

  • Hospital admission longer than 6 hours

  • Lung involvement, as diagnosed on chest X-ray or computed tomography (CT)

  • Confirmed diagnosis of COVID-19

Diagnosis of SARS-CoV-2 infection was confirmed by performing real-time reverse transcription–polymerase chain reaction (RT-PCR) on nasopharyngeal swabs or tracheal aspirate specimens. The test was repeated in patients with negative RT-PCR results if the SARS-CoV-2 infection was still suggested. RT-PCR was performed in accordance with the Centers for Disease Control and Prevention (CDC) and WHO guidelines [5, 6]. The pneumonia diagnosis was confirmed via chest radiographs or lung CT. All pneumonia cases were confirmed by at least two ED physicians and a radiology expert.

A standardised form was used to collect demographic data from the patients as well as data related to the following variables: underlying medical conditions; medications used; clinical signs and symptoms at admission; laboratory tests; and outcomes, including discharge, in-hospital death, intensive care unit (ICU) admission, invasive mechanical ventilation, vasopressor use, renal failure, and renal replacement therapy. Additional information, including vital status during hospitalisation was updated through medical registers. A medical doctor, member of the research team, was responsible for cross-checking information and assuring quality control.

The primary end point was death, and the secondary end points were discharge, ICU admission, need for invasive ventilation, and vasopressor use in patients with COVID-19 pneumonia.

The study protocol was approved by the Research Ethics Committee (REC) of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (protocol number CAAE 30417520.0.0000.0068) with written informed consent or verbal authorization documented in the patient's charts. Patient anonymity was preserved. Written informed consent was not possible, for example, if the patient was unconscious or in acute respiratory failure. When written informed consent from the patient was not possible the REC approved informed verbal authorization from the patient or family members in the presence of witnesses. All patients were treated according to hospital protocols, which included prescription of antibiotics at admission in all cases. The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5

Statistical analysis

Descriptive statistics were calculated for all study variables. Data are expressed as absolute frequencies and percentages for categorical variables. For normally and non-normally distributed continuous variables, data are expressed as means and standard deviations and as medians with interquartile ranges, respectively. The patients' characteristics and outcomes were compared between survivors vs. non-survivors, ICU vs. non-ICU care and intubated vs. non-intubated. We tested univariate associations to the primary outcome with Student’s t-test and the Kruskal–Wallis test for normally distributed and non-normally distributed continuous variables, respectively, whereas the chi-squared test was used to analyse categorical variables. First we applied the chained equations algorithm, that imputes incomplete multivariable data, As a result, five sets of imputed data were obtained [7, 8]. These datasets are stacked in a single matrix. A binomial family model with lasso was fitted [9]. Using the binomial family model with lasso we created a class of penalized objective functions which constructed a homogeneous pooled objective function. We combined the objective functions for each of the imputed datasets together and jointly optimized the collective objective function [9, 10]. All statistical tests were two-sided, and p-values < 0.05 were considered statistically significant. Study data were collected and managed using REDCap electronic data capture tools hosted at this institution [11]. Statistical analyses were performed using StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP and using R version 4.0.3 (2020-10-10), packages miselect and mice.

Definitions

Fever was defined as an axillary temperature of at least 37.8°C. Acute kidney injury was defined according to the clinical practice guidelines of the Kidney Disease Improving Global Outcomes (KDIGO) [12]. The illness severity of COVID-19 was defined according to the WHO guidelines [5]. Extension of pneumonia on CT was classified on an ordinal scale of 1–5 (1: <25%; 2: <50%; 3: 50%; 4: >50%; and 5: >75%), according to the official CT report. The number of comorbidities variable was created adding 1 for each of the following factors: hypertension, diabetes, smoking, hemodialysis, heart conditions (heart failure, atrial fibrillation or other heart diseases), lung conditions (COPD, asthma or lung diseases), cancer, cirrhosis or transplant patient. This variable was capped at 4.

Results

A total of 2219 patients were received in the ED during the study period. Among them, 1193 stayed for at least 6 hours or were admitted to the ED. We confirmed SARS-CoV-2 infection in 518 patients and pneumonia in 506 patients who were enrolled in this study (Fig 1).

Fig 1. Study design and participants.

Fig 1

COVID-19, coronavirus disease; RT-PCR, reverse transcription–polymerase chain reaction.

The demographic and clinical characteristics of the patients are shown in Table 1. Of the included patients, 57.3% were males, and the average age was 59.2 years (±16.8). Bilateral lung involvement was observed in all patients on chest X-ray or CT.

Table 1. Characteristics of the 506 patients with COVID-19 pneumonia at admission to the emergency department.

Variable All patients Survivors Non-survivors P Non-ICU patients ICU patients p Non-intubated patients Intubated patients p
N 506 353 153 206 300 279 227
Age, mean ± SD 60.1±15.1 57.4±14.6 66.2±14.4 <0.0001 58.4±15.5 61.2±14.7 0.0413 59.4±15.6 60.9±14.5 0.274
Females, N (%) 216 (42.7%) 148 (41.9%) 68 (44.4%) 0.599 92 (44.7%) 124 (41.3%) 0.457 126 (45.2%) 90 (39.7%) 0.212
White, N (%) 268 (53.0%) 186 (52.7%) 82 (53.6%) 0.852 164 (54.7%) 104 (50.5%) 0.355 142 (50.9%) 126 (55.5%) 0.301
Symptoms on presentation, N (%)
Dyspnoea 385 (76.1%) 267 (75.6%) 118 (77.1%) 0.719 0.719 154 (74.8%) 231 (77%) 0.561 210 (75.3%) 175 (77.1%) 0.632
Cough 376 (74.3%) 270 (76.5%) 106 (69.3%) 0.088 161 (78.2%) 215 (71.7%) 0.088 210 (75.3%) 166 (73.1%) 0.584
Myalgia 197 (38.9%) 159 (45.0%) 38 (24.8%) <0.0001 98 (47.6%) 99 (33%) 0.001 127 (45.5%) 70 (30.8%) 0.001
Sore throat 75 (14.8%) 60 (17%) 15 (9.8%) 0.036 38 (18.4%) 37 (12.3%) 0.057 48 (17.2%) 27 (11.9%) 0.095
Rhinorrhoea 80 (15.8%) 56 (15.9%) 24 (15.7%) 0.96 32 (15.5%) 48 (16%) 0.888 50 (17.9%) 30 (13.2%) 0.149
Diarrhoea 88 (17.4%) 66 (18.7%) 22 (14.4%) 0.239 47 (22.8%) 41 (13.7%) 0.008 55 (19.7%) 33 (14.5%) 0.127
Nausea 97 (19.2%) 73 (20.7%) 24 (15.7%) 0.19 53 (25.7%) 44 (14.7%) 0.002 65 (23.3%) 32 (14.1%) 0.009
Headache 128 (25.3%) 105 (29.8%) 23 (15.0%) <0.0001 69 (33.5%) 59 (19.7%) <0.0001 88 (31.5%) 40 (17.6%) <0.0001
Dysgeusia 117 (23.1%) 102 (28.9%) 15 (9.8%) <0.0001 66 (32.0%) 51 (17%) <0.0001 86 (30.8%) 31 (13.7%) <0.0001
Anosmia 99 (19.6%) 85 (24.1%) 14 (9.2%) <0.0001 53 (25.7%) 46 (15.3%) 0.004 68 (24.4%) 31 (13.7%) 0.003
Fever 231 (45.7%) 166 (47.0%) 65 (42.5%) 0.346 99 (48.1%) 132 (44.0%) 0.368 131 (46.6%) 100 (44.1%) 0.515
Support during presentation, N (%)
Supplemental oxygen or intubation 404 (82.5%) 272 131 <0.0001 147 256 <0.0001 201 202 <0.0001
Vasopressors on arrival 58 (12.4%) 19 (5.8%) 39 (27.5%) <0.0001 2 (1.0%) 56 (20.4%) <0.0001 4 (1.5%) 54 (25.8%) <0.0001
Vital Signs, mean ± SD
Systolic blood pressure 124.4±23.2 126.4±21.1 119.9±26.9 0.0066 122.0±24.5 128.1±20.5 0.0072 119.5±25.1 128.7±20.4 <0.0001
Diastolic blood pressure 75.1±15.1 76.4±13.7 72.2±17.8 0.0079 73.7±16.1 77.2±13.3 0.0174 72.1±16.9 77.7±12.9 0.0001
Heart rate 88.6±16.4 87.3±16.4 91.8±16.0 0.0062 90.0±16.2 86.5±16.5 0.0203 90.5±16.1 87.0±16.5 0.0208
Respiratory rate 26.0±7.0 26.0±6.8 26.0±7.5 0.942 26.6±7.3 25.1±6.4 0.0311 26.7±7.6 25.4±6.4 0.0702
Blood O2 saturation 92.5±4.9 92.9±4.4 91.5±6.0 0.0055 91.8±5.7 93.6±3.3 0.0001 91.5±6.0 93.4±3.7 <0.0001
Comorbidities, N (%)
None 112 (22.1) 88 (24.9%) 24 (15.7%) 0.0036 41 (19.9%) 71 (23.7%) 0.815 57 (20.4%) 55 (24.2%) 0.217
1 comorbidity 145 (28.7%) 104 (29.5%) 41 (26.8%) - 62 (30.1%) 83 (27.7%) - 78 (28.0%) 67 (29.5%) -
2 comorbidities 142 (28.1%) 88 (24.9%) 54 (35.3%) - 61 (29.6%) 81 (27.0%) - 76 (27.2%) 66 (29.1%) -
3 comorbidities 69 (13.6%) 50 (14.2%) 19 (12.4%) - 28 (13.6%) 41 (13.7%) - 47 (16.9%) 22 (9.7%) -
≥4 comorbidities 38 (7.5%) 23 (6.5%) 15 (9.8%) - 14 (6.8%) 24 (8.0%) - 21 (7.5%) 17 (7.5%) -
Hypertension 280 (55.3%) 192 (54.4%) 88 (57.5%) 0.516 112 (54.4%) 168 (56.0%) 0.717 159 (57.0%) 121 (53.3%) 0.407
Diabetes 181 (35.8%) 119 (33.7%) 62 (40.5%) 0.142 63 (30.6%) 118 (39.3%) 0.044 92 (33.0%) 89 (39.2%) 0.146
Past or current smoker 144 (39.2%) 100 (36.5%) 44 (47.3%) 0.065 62 (36.2%) 82 (41.8%) 0.275 90 (38.5%) 54 (40.6%) 0.687
Renal replacement therapy 15 (3.0%) 8 (2.3%) 7 (4.6%) 0.16 6 (2.9%) 9 (3.0%) 0.955 7 (2.5%) 8 (3.5%) 0.503
Congestive heart failure 39 (7.7%) 25 (7.1%) 14 (9.2%) 0.423 15 (7.3%) 24 (8.0%) 0.766 21 (7.5%) 18 (7.9%) 0.866
COPD 15 (3.0%) 5 (1.4%) 11 (7.2%) 0.002 3 (1.5%) 12 (4.0%) 0.097 7 (2.5%) 8 (3.5%) 0.503
Asthma 22 (4.4%) 14 (4.0%) 10 (6.5%) 0.522 11 (5.3%) 11 (3.7%) 0.365 13 (4.7%) 9 (4.0%) 0.703
Other lung diseases 12 (2.4%) 9 (2.6%) 8 (5.2%) 0.689 4 (1.9%) 8 (2.7%) 0.599 6 (2.2%) 6 (2.6%) 0.717
Cancer 39 (7.7%) 18 (5.1%) 21 (13.7%) 0.001 20 (9.7%) 19 (6.3%) 0.162 25 (9.0%) 14 (6.2%) 0.241
Solid organ transplant 16 (3.2%) 8 (2.3%) 8 (5.2%) 0.08 5 (2.4%) 11 (3.7%) 0.434 7 (2.5%) 9 (4.0%) 0.352
Systemic lupus erythematosus 5 (1.0%) 5 (1.4%) 0 (0%) 0.139 3 (1.5%) 2 (0.7%) 0.378 4 (1.4%) 1 (0.4%) 0.261
HIV 7 (1.4%) 4 (1.1%) 3 (2.0%) 0.464 2 (1.0%) 5 (1.7%) 0.51 3 (1.1%) 4 (1.8%) 0.511
Medications, N (%)
Chloroquine 28 (6.0%) 18 (5.4%) 10 (7.5%) 0.39 5 (2.5%) 23 (8.6%) 0.007 9 (3.4%) 19 (9.6%) 0.005
ACEIs 87 (18.2%) 70 (20.6%) 17 (12.3%) 0.034 41 (20.4%) 46 (16.6%) 0.289 60 (22.0%) 27 (13.2%) 0.014
ARBs 86 (18.2%) 68 (20.1%) 18 (13.3%) 0.084 43 (21.6%) 43 (15.7%) 0.1 60 (22.1%) 26 (12.9%) 0.01
Immunosuppressors 21 (4.9%) 14 (4.5%) 7 (6.0%) 0.51 9 (4.8%) 12 (5.0%) 0.919 13 (5.1%) 8 (4.7%) 0.859
NSAIDs 39 (9.1%) 31 (9.9%) 8 (6.9%) 0.331 20 (10.6%) 19 (7.9%) 0.332 25 (9.7%) 14 (8.2%) 0.588

COVID-19, coronavirus disease; ICU, intensive care unit; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus infection; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II type 1 receptor blockers; NSAIDs, non-steroidal anti-inflammatory drugs

The patients have had the symptoms for 8.5 days on average, before they were admitted to the ED, and 394 (77.9%) patients had at least one comorbidity, of which the most prevalent was hypertension (found in 280 patients– 55.3%), followed by diabetes (found in 181 patients– 35.8%). Almost half of the patients had multiple comorbidities (249 patients– 49.2%). The most common symptoms were dyspnoea (385 patients– 76.1%), cough (376 patients– 74.3%), fever (231 patients– 45.7%), and myalgia (139 patients– 38.9%). In addition, 80 (15.8%) patients had rhinorrhoea and 75 (14.8%) had sore throat. Anosmia and dysgeusia, symptoms that were common in other series, were also present in 117 (23.1%) and 99 (19.6%) patients, respectively [1315], while diarrhoea and nausea were present in 88 (17.4%) and 97 (19.2%).

Among the patients, 417 (82.5%) needed oxygen supplementation in the ED, 62 (12.4%) needed vasopressors immediately after arrival in the ED, and 44 (8.7%) were already intubated upon arrival to the ED.

Similar to other series, lymphopenia, defined as a lymphocyte count < 1500 cells/μL, was quite common 418 patients (82.8%) [5, 6]. D-dimer levels were elevated in 83.5% of patients. Levels of lactate dehydrogenase, C-reactive protein, cardiac troponin T, and creatine phosphokinase were also elevated in 446 patients (88.2%), 320 (63.4%), 193 (38.3%), and 138 (27.4%), respectively. Laboratory test results are shown in Table 2.

Table 2. Laboratory test results of patients with COVID-19 pneumonia.

Variable All patients Survivors Non-survivors P Non-ICU patients ICU patients p Non-intubated patients Intubated patients p
Hb (n = 506) (g/dL) 12.4±2.2 12.7±1.9 11.9±2.6 0.0002 12.3±2.3 12.5±2.1 0.4973 12.5±2.2 12.4±2.2 0.5325
Neutrophils (n = 506) (cells/m3 × 103) 6850±4200 6200±3400 8400±5200 <0.0001 5200±2900 7900±4500 <0.0001 5600±3000 8300±4700 <0.0001
Lymphocytes (n = 430) (cells/m3 × 103) 1001±540 1077±553 825±464 <0.0001 1130±532 921±530 0.0001 1093±514 900±551 0.0002
Lymphopenia (<1500) 356 (82.8%) 242 (80.1%) 114 (89.1%) 0.025 125 (75.3%) 231 (87.5%) 0.001 176 (77.9%) 180 (88.2%) 0.004
Platelets (n = 468) (cells/m3 × 103) 219,000±87,000 223,000±86,000 208,000±90,000 0.0947 221,000±86,000 217,000±88,000 0.6331 219,000±84,000 218,000±91,000 0.9538
Creatinine (n = 470) (mg/dL) 1.5±1.7 1.2±1.3 2.3±2.3 <0.0001 1.2±1.5 1.7±1.8 0.0024 1.2±1.3 1.9±2.0 <0.0001
Creatinine (>1.2 mg/dL) 160 (34%) 81 (24.7%) 79 (55.2%) <0.0001 40 (21.7%) 120 (42.0%) <0.0001 56 (22.5%) 104 (47.1%) <0.0001
D-dimer (n = 383) (U/L) 1278 (676–2569)* 1136 (630–2057)* 1851 (850–4676)* <0.0001 963 (580–1569)* 1467 (750–3948)* <0.0001 977 (565–1554)* 1694 (835–4284)* <0.0001
Elevated D-dimer (>500 U/L) 332 (86.7%) 232 (83.5%) 100 (95.2%) 0.002 122 (80.8%) 210 (90.5%) 0.006 162 (80.2%) 170 (93.9%) 0.0001
C-reactive protein (n = 436) (mg/dL) 171±111 154±102 210±120 <0.0001 115±84 207±111 <0.0001 124±83 222±115 <0.0001
Elevated C-reactive protein (>100 mg/dL) 299 (68.6%) 194 (63.4%) 105 (80.8%) <0.0001 80 (46.5%) 219 (83.0%) <0.0001 123 (53.5%) 176 (85.4%) <0.0001
AST (n = 418) (U/L) 42 (30–61)* 39 (28–58)* 50 (34–74)* 0.0005 36 (27–55) 44 (33–67)* 0.0004 38 (27–55)* 50 (33–72)* 0.0001
AST (>40 U/L) 219 (52.4%) 138 (47.6%) 81 (63.3%) 0.003 73 (44.8%) 146 (57.3%) 0.013 96 (44.4%) 123 (60.9%) 0.001
LDH (n = 373) (U/L) 467±417 417±246 586±399 <0.0001 375±271 529±317 <0.0001 387±251 562±341 <0.0001
LDH (>250 U/L) 337 (90.3%) 232 (88.2%) 105 (95.5%) 0.031 126 (84.0%) 211 (94.6%) 0.001 174 (86.6%) 163 (94.8%) 0.008
CPK (U/L) 854±3669 680±3908 1260±3024 0.2623 380±1865 1118±4347 0.1354 315±1584 1392±4893 0.0227
CPK (>200 U/L) 82 (34.2%) 46 (27.4%) 36 (50.0%) 0.001 20 (23.3%) 62 (40.3%) 0.008 25 (20.8%) 57 (47.5%) <0.0001
Troponin T (n = 314) (ng/L) 15 (8–45)* 11 (7–20)* 38 (15–96)* 0.0001 11 (7–23)* 17 (9–56)* 0.0009 11 (7–22)* 21 (10–83)* 0.0001
Elevated troponin 157 (50.0%) 83 (38.3%) 74 (76.3%) <0.0001 47 (40.2%) 110 (55.8%) 0.007 61 (38.6%) 96 (61.5%) <0.0001

Number in parenthesis indicates number of patients who had that test ordered in the emergency department.

* Median and interquartile-range. COVID-19, coronavirus disease;, ICU, intensive care unit; Hb, haemoglobin; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; CPK, creatine phosphokinase.

Outcomes

We found that 153 patients died (30.2%), 333 were discharged home (65.9%), and 20 (3.9%) remained in the hospital when we finalised data collection on August 27, 2020 (Table 2). A total of 300 of the 506 patients (59.3%) required ICU admission, 227 (44.9%) needed invasive ventilation, 179 (35.4%) needed vasopressors, and 68 (13.4%) required dialysis. Of the 353 survivors, 165 patients (46.7%) went through the ICU stay, 65 (18.4%) used vasopressors and 19 (5.4%) needed haemodialysis. All-cause mortality in patients not admitted to the ICU was 18 patients (8.7%), and in patients who did not need intubation, it was 26 (9.3%). In patients admitted to the ICU, 135 patients (45%) died, while 127 (56%) died in the intubated patients. Of all the patients on vasopressors, 114 (63.7%) died. Of all the patients on dialysis, 49 (72,1%) died. The median time from illness onset to ED evaluation was 8 days, and that from onset to home discharge was 22.1 days. The median length of hospital stay was 11 days (Fig 2).

Fig 2. Timeline of coronavirus disease (COVID-19) cases after onset of illness.

Fig 2

*: ICU intensive care unit.

Comparison between survivors and non-survivors

Survivors were significantly younger than non-survivors (57.4 vs 66.2 years old). Myalgia (159 patients [45.0%] vs 38 patients [24.8%]), sore throat (60 [17.0%] vs 15 [9.8%]), headache (105 [29.8%] vs 23 [15.0%]), dysgeusia (102 [28.9%] vs 15 [9.8%]), and anosmia (85 [24.1%] vs 14 [9.2%]) were significantly more frequent among survivors. In our univariate analysis low blood pressure, high cardiac rate, and hypoxia were associated with an increased risk of death, ICU admission, or invasive ventilation (Table 1).

There were significantly higher levels of C-reactive protein, lactate dehydrogenase, neutrophils, and troponin T and lower levels of lymphocytes in: non-survivors than that in survivors, in patients admitted to the ICU than that in those not admitted to the ICU, and in intubated patients than that in those who were not intubated.

In this study, the D-dimer levels were high, with 332 (86.7%) patients having levels higher than 500 μg/dL, and with survivors having a median level of 1136 U/L, compared with 1851 U/L in non-survivors. Admission troponin T was available for 314 patients, and in 157 (50%) it was elevated. Median cardiac troponin T for survivors was 11 ng/L, while it was 38 ng/L for non-survivors. In survivors, 83 (38.3%) had an elevated troponin T level, while 74 (76.3%) had an elevated troponin T level in non-survivors.

Patients who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) at home had lower odds ratio for mortality. While chloroquine was not prescribed for COVID-19 treatment in our institution, 28 patients who arrived in our ED were already using that. Of those, we continued chloroquine in six patients who were taking it or hydroxychloroquine at home, while we suspended the medication for the others. Although we observed that chloroquine or hydroxychloroquine was associated with increased mortality, but because the number of patients was only 28, we could not draw any meaningful conclusion.

Table 3 shows that of the 300 patients admitted to the ICU, 135 (45.0%) died, 146 (48.7%) were discharged, and 19 (6.3%) remained in the hospital. Meanwhile, of the 227 patients who needed invasive ventilation, 127 (55.9%) died, 82 (36.1%) were discharged home, and 18 (7.9%) remained in the hospital.

Table 3. Mechanical ventilation, ICU admission and all-cause mortality of patients with COVID-19 pneumonia.

Outcomes All patients Survivors Non-survivors ICU patients Non-ICU patients Intubated patients Non intubated Vasopressors Dialytic patients
N 506 353 153 300 206 227 279 179 68
Orotracheal intubation 227 (44.9%) 100 (28.3%) 127 (83.0%) 226 (75.3%) 170 (94.5%) 65 (98.5%)
ICU 300 (59.3%) 165 (46.7%) 135 (88.2%) 226 (99.6%) 74 (26.5%) 179 (100%) 68 (100%)
Vasopressor 179 (35.4%) 65 (18.4%) 114 (74.5%) 179 (59.7%) 170 (74.9%) 9 (3.2%) 66 (97.1%)
Haemodialysis 68 (13.4%) 19 (5.4%) 49 (32.0%) 68 (22.7%) 67 (29.5%) 1 (0.4%) 66 (36.9%)
All-cause mortality 153 (30.2%) 135 (45.0%) 18 (8.7%) 127 (55.6%) 26 (9.3%) 114 (63.7%) 49 (72.1%)

The mortality rate in patients who needed vasopressors and dialysis support was 63.7% (114 deaths out of 179 patients on vasopressors) and 72.1% (49 deaths out of 68 patiens on haemodialysis), respectively. Fifty-two (29.1%) of the patients who needed vasopressors were discharged home, while only 12 of those who needed dialysis were discharged home (17.6%).

A multivariate analysis revealed that age, number of comorbidities, increased extension of ground glass on CT, increased troponin T were associated with all-cause mortality whereas use of angiotensin converting enzyme inhibitor, use of angiotensin II receptor blocker, higher number of lymphocytes, and dysgeusia were associated with decreased all-cause mortality (Table 4).

Table 4. Multivariate predictors of the risk of death.

Multivariate predictor Beta coefficient
Intercept -3.406
Age .036
Dysgeusia -0.801
Comorbidities 0.253
Use of ACEIs -1.332
Use of ARBs -1.104
Lymphocytes -0.802
Troponin T 3.062
Extension of ground glass on CT 0.381

CI, confidence interval; CT, computed tomography; ACEIs, angiotensin-converting enzyme inhibitors, ARBs, angiotensin II type 1 receptor blockers

* lambda of 0,0007498653 and deviance of 0,9156566

We applied our final model back on our population to gage the multivariate model. We found a sensitivity of 81%, specificity of 71% for all-cause mortality. The negative predictive value was 87% while the positive predictive value was 62% and the AUC was 0.82 (0.78–0.86).

Discussion

This prospective study evaluated a cohort of patients who presented to the ED with severe COVID-19. Among the patients, 59.2% were admitted to the ICU and 41.5% needed mechanical ventilator support, far greater than the corresponding percentages in other series. Unlike other published cohorts, the vast majority (96%) of patients in this study have already had a defined outcome [1619].

In the largest ICU series of cases from Lombardy in Italy, 58.2% of patients remained in the ICU. When only patients with defined outcomes were evaluated, the mortality in the ICU was 62.2% [20] Data from the Brazilian Society of Intensive Care shows that ICU mortality in public hospitals is 51.7% and 29.1% in private hospitals [21]. In our study we found 45.0% ICU mortality, which is better than other series, but not as good as that recorded for private hospitals in this country. Moreover, the mortality of intubated patients in our study was high, at 55.9%, while only 36.1% of these patients were discharged. This mortality rate is still lower than that of some of the largest series of cases, such as the New York City series, which had a mortality rate of 88.8% for intubated patients [18]. Other series showed mortality rates of intubated patients as high as 97% [2224]. Another study however, found a considerably lower mortality rate of approximately 35% in intubated patients [25].

In our univariate analysis, we found that levels of cardiac troponin T, D-dimer, and changes to other laboratory markers were associated with mortality, mechanical ventilation, and ICU admission. There were 55 patients with D-dimer levels over 5000 U/L, ranging from 5260 to 107,138 U/L. Zhou and colleagues found that D-dimer levels were higher than 1000 μg/dL in 82% of non-survivors, compared with 24% of survivors, in a case series of COVID-19 pneumonia [26]. Troponin increase likely reflects increased acute coronary syndrome secondary to infectious state but also myocardial injury secondary to COVID-19-related prothrombotic and proinflammatory states [27].

The LASSO multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality In different studies older age, hypertension, diabetes melitus, dyspnea, number of comorbidities, and laboratory parameters were associated to increased risk of mortality in patients with COVID-19 [28, 29]. The symptoms at presentation in our study were not significantly different compared with those of other large studies [16, 30], even considering that our patients had, on average, more severe disease. This finding is unsurprising because most of the symptoms were not significantly different among survivors and non-survivors except for myalgia, headache, anosmia, and dysgeusia associated with lower mortality in an univariate analysis, while dysgeusia remained significant in the multivariate analysis. To our knowledge, this is the first study that found such association. In a cohort of 345 patients, of whom a high proportion had olfactory and gustatory function impairment, there were no significant differences in the severity of disease and outcomes in patients with such impairment [31].

COVID-19 may have a progressive evolution. Huang and colleagues reported that patients with COVID-19 were admitted to the ICU after 11 days of symptoms [1, 26] and intubated after 12 days of symptoms. In our cohort, this timeline was a little shorter–our patients were admitted to the ICU and were intubated in a median of 8.7 days and 8.9 days, respectively, after the onset of symptoms.

Interestingly, patients who were taking ACEIs or ARBs at home had a reduced mortality. ACEIs or ARBs do not increase the risk of COVID-19 [32]. Some studies have suggested a potential beneficial effect of RAS inhibitors in SARS-CoV-2 patients, and this has been put forward in some reviews [3338]. SARS-CoV-2 enters type 2 pneumocytes in humans through angiotensin-converting enzyme 2 receptors [39]. Several studies, including our own, showed hypertension as the most common comorbidity associated with COVID-19 [16, 18, 30]. In this study, typical patients with severe COVID-19 had their antihypertensives suspended on admission and reintroduced upon stabilisation of blood arterial pressure, usually on discharge to the ward. New studies are necessary to test the association of ACEIs and ARBs with COVID-19 outcomes. The PRAETORIAN-COVID trial that is a double-blind, placebo-controlled randomised clinical trial of valsartan to prevent acute respiratory distress syndrome in hospitalised patients with SARS-COV-2 infection, may help to solve this question [40]. The BRACE CORONA trial evaluated temporary interruption of ACEi/ARB at COVID-19 diagnosis. They evaluated a low risk cohort–they reported general all-cause mortality was 2.74%. They found no difference in number of days alive and out of hospital through 30 days or all-cause mortality. A hypothesis that could be made is that the ACEi/ARB benefit we observed is because of the severity of our cohort [41]. The benefit we observed could be a statistical fluke and would need to be confirmed in other cohorts for validaiton.

Our study has some limitations. It was a single-centre study, and patients from other EDs were referred to our ED. Furthermore, our patients had COVID-19 that was more severe than what would be ordinarily expected in the ED [1619].

In conclusion, this is a case series of older patients with multiple comorbidities presenting with moderate and severe COVID-19 pneumonia in São Paulo city, Brazil. The majority were admitted to the ICU and many were intubated, treated with vasopressors, and haemodialysis. All-cause mortality was 30% for the entire series, 45% for patients admitted to the ICU and 56% for the intubated patients. Finally, we tested the model in the same database from which the model was derived.

Preparation to adequately treat patients with severe COVID-19 involves providing not only large numbers of ICU beds but also warrants a high capacity to provide mechanical ventilation, vasopressors, and haemodialysis.

Supporting information

S1 Data

(XLS)

Acknowledgments

The Emergencia USP Covid Group is composed by

Felipe Liger Moreira, MD**1, Edwin Albert D’Souza*1, Arthur Petrillo Bellintani*1, Rodrigo Cezar Miléo*1, Rodrigo Werner Toccoli*1, Fernanda Máximo Fonseca e Silva*1, João Martelleto Baptista*1, Marcelo de Oliveira Silva*1, Giovanna Babikian Costa*1, Rafael Berenguer Luna*1, Henrique Tibucheski dos Santos*1, Mariana Mendes Gonçalves Cimatti De Calasans*1, Marcelo Petrof Sanches*1, Diego Juniti Takamune*1, Luiza Boscolo*1, Pedro Antonio Araújo Simões*1, Manuela Cristina Adsuara Pandolfi*1, Beatriz Larios Fantinatti*1, Gabriel Travessini*1, Matheus Finardi Lima de Faria*1, Ligia Trombetta Lima*1, Bianca Ruiz Nicolao*1, Gabriel de Paula Maroni Escudeiro*1, João Pedro Afonso Nascimento*1, Everton Luis Santos Moreira*1, Erika Thiemy Brito Miyaguchi *1, Bruna Tolentino Caldeira*1, Laura de Góes Campos*1, Vitor Macedo Brito Medeiros*1, Tales Cabral Monsalvarga*1, Isabela Harumi Omori*1, Diogo Visconti Guidotte*1, Alexandre Lemos Bortolotto*1, Rodrigo de Souza Abreu*1, Nilo Arthur Bezerra Martins*1, Carlos Eduardo Umehara Juck*1, Natalia Paula Cardos*1, Osvaldo Santistevan Claure*1, João Vitor Ziroldo Lopes*1, Felipe Mouzo Bortoleto**, MD1, Gabriel Martinez**, MD1, Lucas Gonçalves Dias Barreto**, MD1, Debora Lopes Emerenciano**, MD1, Daniel Rodrigues Ribeiro**, MD1, Danilo Dias de Francesco**, MD1, Eduardo Mariani Pires de Campos**, MD1, Stefany Franhan Barbosa de Souza**, MD1, Geovane Wiebelling da Silva**, MD1, Andrew Araujo Tavares**, MD1, Clara Carvalho de Alves Pereira**, MD1, Ademar Lima Simões**, MD1, Gustavo Biz Martins**, MD1, Maria Lorraine Silva de Rosa**, MD1, Thiago Areas Lisboa Netto**, MD1, Julio Cesar Leite Fortes**, MD1, Rafael Faria Pisciolaro**, MD1, Mauricio Ursoline do Nascimento**, MD1, Rodolfo Affonso Xavier**, MD1, Yago Henrique Padovan Chio**, MD1, Patricia Albuquerque de Moura***, BS1, Emily Cristine Oliveira Silva***, BS1, Ester Minã Gomes da Silva***, BS1, Yasmine Souza Filippo Fernandes***, BS1, Renata Kan Nishiaka***, BS1,

* Medical Student

** Emergency medicine resident

*** Respiratory physiotherapy specialist

1Emergency Department, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Data Availability

All data has been submitted here.

Funding Statement

Dr. Gomez was supported by FAPESP grant #2019/23078-1.

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Decision Letter 0

Walter R Taylor

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

27 Oct 2020

PONE-D-20-29947

Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: a prospective observational Brazilian study.

PLOS ONE

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Reviewer #1: Thank you for the opportunity to review this paper. It is good to read a report describing presentations with COVID-19 that does not come from one of the countries that have tended to dominate the literature on this topic. Overall, the study provides a useful addition to the emerging literature on acute presentations with COVID-19. I have the following suggestions that I hope the authors will find helpful.

Please state the aim and specific objectives of the study at the end of the introduction, ensuring that the objectives are in accordance with the analysis undertaken (i.e. to describe the characteristics of people admitted to hospital with COVID-19 pneumonia and identify independent predictors of adverse outcome).

Under study design, it would be helpful to know the population covered by the hospital. Did the hospital act as the referral centre for the whole of Sao Paulo and, if so, what is the population of Sao Paulo?

Non-invasive ventilation is not reported in the outcomes. There have been reports that non-invasive ventilation (including CPAP) can reduce the need for ventilation and suggestions that this may improve outcomes. Are you able to comment on the use of non-invasive ventilation in your hospital?

Please clarify the duration of follow up? Presumably patients were follow until death or hospital discharge, but a proportion were still in hospital at a specified date.

How were the 2219 ED attendances selected? I presume these were patients with suspected COVID-19, so how was that defined? I also assume that only those admitted were routinely tested for COVID-19, but please clarify this.

It would be interesting to compare the characteristics and outcomes of those admitted with confirmed COVID-19 to those with negative COVID-19 testing. Maybe this is planned for a separate analysis.

I recommend reporting numbers alongside the percentages in the results text.

The description of the multivariable analysis requires some more detail to allow it to be reproducible:

1. How were missing predictor variables handled (I assume those with missing outcomes were excluded from the analysis)? Were missing data assumed to be normal? This may require some more information regarding the recording of predictor variables, perhaps by providing the data collection form as an appendix.

2. How was the relationship between continuous predictor variables and outcome modelled, given that some may have non-linear relationships with outcome?

3. How many predictor variables were included in the analysis? The sample size may be insufficient for a large number of predictor variables, and including too many may lead to over-fitting.

4. Was any analysis undertaken to validate the multivariable model?

In general, I think the multivariable analysis is the weakest part of the study. The descriptive analysis is appropriate and clearly presented, allowing readers to understand the characteristics of your population and compare it to other populations. It is more difficult to draw conclusions from the multivariable analysis. The study may lack power for multivariable analysis, creating risks of important predictors being missed, while the model may be over-fitted if too many predictor variables were included. I would either drop the multivariable analysis from the paper or, if retained, ensure the analysis is clearly described and the limitations acknowledged.

Finally, PLOS ONE has reviewed a paper from my research team describing ED attendances with suspected COVID-19 across the UK. You may wish to contrast your findings with ours in your discussion. The pre-print is available here (https://www.medrxiv.org/content/10.1101/2020.08.10.20171496v1) and I am happy to share our revised paper, if this is OK with the PLOS ONE editors.

Steve Goodacre, 12 October 2020

**********

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Reviewer #1: Yes: Steve Goodacre

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PLoS One. 2021 Jan 7;16(1):e0244532. doi: 10.1371/journal.pone.0244532.r002

Author response to Decision Letter 0


4 Dec 2020

Comments from the editor:

Comment #1: Whether the Institutional Review Board approved the use of verbal authorization from the patient or family was obtained in the presence of witnesses. How verbal authorization from the patient or family was documented.

Response #1: In document #4.1119.252 from the HCFMUSP research ethics committee approved that verbal authorization can be obtained in the presence of witnessess and this should be documented in the patient's chart.

Comment #2: One of the noted authors is a group; Emergencia USP Covid group.

In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript.

Please also indicate clearly a lead author for this group along with a contact email address.

Response #2: We have included this infomartion in the acknowledgements section and included more information on their affiliations

Original version:

Emergencia USP Covid Group

Felipe Liger Moreira, MD1 , Edwin Albert D’Souza*1 , Arthur Petrillo Bellintani*1 , Rodrigo Cezar Miléo*1 , Rodrigo Werner Toccoli*1, Fernanda Máximo Fonseca e Silva*1, João Martelleto Baptista*1 , Marcelo de Oliveira Silva*1 , Giovanna Babikian Costa*1 , Rafael Berenguer Luna*1 , Henrique Tibucheski dos Santos*1 , Mariana Mendes Gonçalves Cimatti De Calasans*1, Marcelo Petrof Sanches*1 , Diego Juniti Takamune*1 , Luiza Boscolo*1 , Pedro Antonio Araújo Simões*1 , Manuela Cristina Adsuara Pandolfi*1 , Beatriz Larios Fantinatti*1 , Gabriel Travessini*1 , Matheus Finardi Lima de Faria*1 , Ligia Trombetta Lima*1 , Bianca Ruiz Nicolao*1 , Gabriel de Paula Maroni Escudeiro*1 , João Pedro Afonso Nascimento*1 , Everton Luis Santos Moreira*1 , Erika Thiemy Brito Miyaguchi *1 , Bruna Tolentino Caldeira*1 , Laura de Góes Campos*1 , Vitor Macedo Brito Medeiros*1 , Tales Cabral Monsalvarga*1 , Isabela Harumi Omori*1 , Diogo Visconti Guidotte*1 , Alexandre Lemos Bortolotto*1 , Rodrigo de Souza Abreu*1 , Nilo Arthur Bezerra Martins*1 , Carlos Eduardo Umehara Juck*1 , Felipe Mouzo Bortoleto, MD1 , Gabriel Martinez, MD1 , Lucas Gonçalves Dias Barreto, MD1 , Debora Lopes Emerenciano, MD1 , Daniel Rodrigues Ribeiro, MD1 , Danilo Dias de Francesco, MD1 , Eduardo Mariani Pires de Campos, MD1 , Stefany Franhan Barbosa de Souza, MD1 , Geovane Wiebelling da Silva, MD1 , Andrew Araujo Tavares, MD1 , Clara Carvalho de Alves Pereira, MD1 , Ademar Lima Simões, MD1 , Gustavo Biz Martins, MD1 , Maria Lorraine Silva de Rosa, MD1 , Thiago Areas Lisboa Netto, MD1 , Julio Cesar Leite Fortes, MD1 , Rafael Faria Pisciolaro, MD1 , Mauricio Ursoline do Nascimento, MD1 , Rodolfo Affonso Xavier, MD1 , Yago Henrique Padovan Chio, MD1 , Patricia Albuquerque de Moura, BS1 , Emily Cristine Oliveira Silva, BS1 , Ester Minã Gomes da Silva, BS1 , Yasmine Souza Filippo Fernandes, BS1 , Renata Kan Nishiaka, BS1 ,

* Medical Student

1Emergency Department, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Revised version:

Acknowledgements

The Emergencia USP Covid Group is composed by

Felipe Liger Moreira, MD**1 , Edwin Albert D’Souza*1 , Arthur Petrillo Bellintani*1 , Rodrigo Cezar Miléo*1 , Rodrigo Werner Toccoli*1, Fernanda Máximo Fonseca e Silva*1, João Martelleto Baptista*1 , Marcelo de Oliveira Silva*1 , Giovanna Babikian Costa*1 , Rafael Berenguer Luna*1 , Henrique Tibucheski dos Santos*1 , Mariana Mendes Gonçalves Cimatti De Calasans*1, Marcelo Petrof Sanches*1 , Diego Juniti Takamune*1 , Luiza Boscolo*1 , Pedro Antonio Araújo Simões*1 , Manuela Cristina Adsuara Pandolfi*1 , Beatriz Larios Fantinatti*1 , Gabriel Travessini*1 , Matheus Finardi Lima de Faria*1 , Ligia Trombetta Lima*1 , Bianca Ruiz Nicolao*1 , Gabriel de Paula Maroni Escudeiro*1 , João Pedro Afonso Nascimento*1 , Everton Luis Santos Moreira*1 , Erika Thiemy Brito Miyaguchi *1 , Bruna Tolentino Caldeira*1 , Laura de Góes Campos*1 , Vitor Macedo Brito Medeiros*1 , Tales Cabral Monsalvarga*1 , Isabela Harumi Omori*1 , Diogo Visconti Guidotte*1 , Alexandre Lemos Bortolotto*1 , Rodrigo de Souza Abreu*1 , Nilo Arthur Bezerra Martins*1 , Carlos Eduardo Umehara Juck*1 , Felipe Mouzo Bortoleto**, MD1 , Gabriel Martinez**, MD1 , Lucas Gonçalves Dias Barreto**, MD1 , Debora Lopes Emerenciano**, MD1 , Daniel Rodrigues Ribeiro**, MD1 , Danilo Dias de Francesco**, MD1 , Eduardo Mariani Pires de Campos**, MD1 , Stefany Franhan Barbosa de Souza**, MD1 , Geovane Wiebelling da Silva**, MD1 , Andrew Araujo Tavares**, MD1 , Clara Carvalho de Alves Pereira**, MD1 , Ademar Lima Simões**, MD1 , Gustavo Biz Martins**, MD1 , Maria Lorraine Silva de Rosa**, MD1 , Thiago Areas Lisboa Netto**, MD1 , Julio Cesar Leite Fortes**, MD1 , Rafael Faria Pisciolaro**, MD1 , Mauricio Ursoline do Nascimento**, MD1 , Rodolfo Affonso Xavier**, MD1 , Yago Henrique Padovan Chio**, MD1 , Patricia Albuquerque de Moura***, BS1 , Emily Cristine Oliveira Silva***, BS1 , Ester Minã Gomes da Silva***, BS1 , Yasmine Souza Filippo Fernandes***, BS1 , Renata Kan Nishiaka***, BS1 ,

* Medical Student

** Emergency medicine resident

*** Respiratory physiotherapy specialist

1Emergency Department, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Comment #3: We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 3 in your text; if accepted, production will need this reference to link the reader to the Table.

Response #3: Thank for pointing out this out. We are now referencing Table 3 in the text.

Original text:

Of the 300 patients admitted to the ICU, 135 (45.0%) died, 146 (48.7%) were discharged, and 19 (6.3%) remained in the hospital.

Revised text:

Table 3 shows that of the 300 patients admitted to the ICU, 135 (45.0%) died, 146 (48.7%) were discharged, and 19 (6.3%) remained in the hospital.

Comment #4: Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information

Response #4: Our full database has been made available to PLOS ONE. I have translated any portuguese terms into english and reupdated the new version.

Attachment

Submitted filename: Plosone_2Rev_Response_to_Reviewers.docx

Decision Letter 1

Walter R Taylor

14 Dec 2020

Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: a prospective observational Brazilian study.

PONE-D-20-29947R1

Dear Dr. Marchini,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Walter R. Taylor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Dr. Marchini,

thankyou for the revision of this paper.

I am happy to accept it for publication.

yours sincerely,

Walter Taylor.

Reviewers' comments:

Acceptance letter

Walter R Taylor

16 Dec 2020

PONE-D-20-29947R1

Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: a prospective observational Brazilian study

Dear Dr. Marchini:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Walter R. Taylor

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Data

    (XLS)

    Attachment

    Submitted filename: Plosone_2Rev_Response_to_Reviewers.docx

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    All data has been submitted here.


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