key: cord-0811566-fv4qonnf
authors: Zhu, Wanbo; Xie, Kai; Lu, Hui; Xu, Lei; Zhou, Shusheng; Fang, Shiyuan
title: Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China
date: 2020-03-24
journal: J Med Virol
DOI: 10.1002/jmv.25763
sha: b9632f2268a31399f304f4a0b58471e2d2fcaab4
doc_id: 811566
cord_uid: fv4qonnf

With an increasing number of Coronavirus Disease 2019 (COVID‐19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID‐19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID‐19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground‐glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.

2019-nCoV shares over 79% of its genome sequence with the coronavirus that causes severe acute respiratory syndrome (SARS-CoV), a member of the subgenus Sarbecovirus (Beta-CoV lineage B); owing to the overall similarity between both viruses, 2019-nCoV was renamed to SARS-CoV-2. 5 Based on the available evidence, it appears that SARS-CoV-2 can be transmitted by asymptomatic carriers, which contributes to its basic reproduction number (R 0 ) and pandemic potential. 6, 7 In addition to the high R 0 of SARS-CoV-2, the convenience of modern means of transportation further enhance its global spread. COVID-19 is still spreading rapidly in China and globally, with 80 993 confirmed cases and 2761 deaths as of 26 February 2020. COVID-19 has become a public health emergency of international concern, and several Asian and European countries (such as Japan and Italy) are registering increases in the number of infected patients. 8, 9 With the increase in the number of confirmed cases outside of Hubei, emergency departments (EDs) and fever clinics around the world are having to accommodate a large number of patients. Preliminary diagnosis based on initial clinical features may contribute to disease control and prevention of further infection, especially in areas with limited access to rapid nucleic acid amplification tests. 10 However, in a recent report by Li, COVID-19 patients outside Hubei exhibited relatively mild symptoms, indicating that the severity of SARS-CoV-2 infection is variable. 11 Chest computed tomography (CT) has a high diagnostic value in the evaluation of COVID-19 patients. However, severe lung abnormalities are only apparent on chest CT scans approximately 10 days after the onset of symptoms. 12 This poses a challenge for the early diagnosis and intervention in patients with suspected COVID-19 in the ED until a confirmation is obtained through real-time reverse-transcription polymerase chain 

The date of illness onset and duration of observation were collected for each patient. Epidemiological data were collected from brief interviews with the patient. Several investigators interviewed each suspected patient on admission to collect exposure histories during the 2 weeks before illness onset. All interviews were performed before an ultimate diagnosis was made. Clinical and laboratory data on admission were obtained from detailed medical records, collected in a standardized case report form by two experienced emergency doctors. Clinical data collected included demographic characteristics, symptoms of infection (such as cough, expectoration, chest pain, and weakness) and presence of comorbidities. Laboratory tests included a complete blood count, serum biochemistry, interleukin-6 (IL-6) test, creatine kinase test, lactate dehydrogenase test, and tests for the identification of other respiratory pathogens. Chest CT examinations were performed upon ED admission in all patients with suspected disease. Two certified chest radiologists independently reviewed the CT images while blinded to the names and clinical data of the patients. Not all patients presented at the same infection stage and some data were missing; thus, data could not be integrated. 

In total, 116 patients with the suspected disease were included in the study. Thirty-two patients were confirmed to have COVID-19 and referred to as "diagnosed patients"; the remaining 84 patients were referred to as "negative cases." The median age for diagnosed patients was 46 years, and 35 years for negative cases (Table 1) . There was a slight female predominance in both groups. There were 6 (19%) smokers among diagnosed patients and 13 (15%) among negative cases. Seven (22%) diagnosed and 15 (18%) negative cases had hypertension. Four (13%) diagnosed and 6 (7%) negative cases had diabetes. There were no other commonly found comorbidities in either group. There was no specific exposure history common to all patients with suspected disease: 8 (25%) diagnosed patients had visited Wuhan in the previous 2 weeks and 12 (38%) had been exposed to patients with infection in the previous 2 weeks. In negative cases, these numbers were 7 (20%) and 8 (24%), respectively. None of the patients had a history of exposure to the seafood market in Wuhan. Median time from illness onset to ED admission for all patients with the suspected disease was 5 (IQR, 2-7), 5 (IQR,4-7), and 4 (IQR,1-9) for all patients, diagnosed patients, and negative cases, respectively.

Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. The cough was the second most commonly observed symptom, found in 21 (66%) diagnosed patients and in 52 (62%) negative cases. Myalgia or fatigue seemed more common in diagnosed patients (16%) than in negative cases (7%). Although the number of negative cases (17) with expectoration was twice as high as that of diagnosed patients (5) 

Laboratory tests on admission showed that 7 (22%) diagnosed and 4 (5%) negative cases had leukopenia (white blood cell count <3.5 × 10 9 /L), 3 (9%) diagnosed and 16 (19%) negative cases had neutrophilia (neutrophil count >6.3 × 10 9 /L) and 19 (59%) diagnosed and 24 (29%) negative cases had lymphopenia (lymphocyte count <1.1 × 10 9 /L) ( Table 2 ). Ten (31%) diagnosed and 29 (35%) negative cases had decreased lymphocyte percentages. Increased D-dimer levels were observed in 3 (9%) diagnosed and 9 (11%) negative cases.

In terms of sensitive indicators of infection, increased procalcitonin levels were found only in 5 (6%) negative cases. The erythrocyte sedimentation rate (ESR) was elevated in 16 (50%) diagnosed patients and 16 (19%) negative cases. Increased C-reactive protein (CRP) levels were confirmed in 21 (66%) diagnosed and 40 (48%) negative cases, while IL-6 levels were elevated in 7 (22%) diagnosed and 7 (8%) negative cases. The results of these indicators were not integrated, owing to different infection stages and missing data. Note: Data are n(%), n/N (%), mean ± SD (minimum-maximum) or and median (IQR), where N is the total number of patients with available data. Abbreviation: BMI, basal metabolic index; ED, emergency department; IQR, interquartile range; SD, standard deviation.

COVID-19 who presented in EDs and fever clinics for the first time.

In total, 32 patients were eventually diagnosed with SARS-CoV-2 infection ("diagnosed patients"). Similar to the confirmed cases in Hubei, the patients who were eventually found to be infected were older than the ones who were not infected: most diagnosed patients were middle-aged or older adults and most negative cases were young or middle-aged patients. 14 However, patients of all age groups have been found to be infected with SARS-CoV-2, and the proportion of older adults among diagnosed and negative cases was similar.

Smokers were equally distributed in both groups, indicating that smoking is not a specific risk factor for diagnosed patients. Note: Data are n(%), n/N (%), mean ± SD (minimum-maximum) or and median (IQR), where N is the total number of patients with available data. Abbreviation: ED, emergency department; IQR, interquartile range; SD, standard deviation. *Percentages do not total 100% owing to missing data.

decreased lymphocyte count (59%) and increased ESR (50%) and CRP (66%) levels.

Having initial clinical symptoms, fever being the most common is the main reason for visiting the ED. 15 In our study, fever and cough were the most common symptoms observed in all patients with suspected disease. Due to the high seasonal incidence of respiratory diseases, these were not atypical manifestations. At the same time, not all patients with suspected disease in our study presented with high temperature when they first visited the ED, despite claims of fever symptoms. This may be attributed to the use of over-thecounter antipyretic drugs. On the 2nd day of clinical quarantine and observation in the ED, febrile symptoms were more accentuated among diagnosed patients, likely due to strict control of antipyretic drugs imposed by physicians, but this observation requires further confirmation. It should also be noted that fever and cough are not present in all confirmed cases, especially outside of Hubei. Similar to previous reports, we found that the initial clinical manifestations tended to be mild in Anhui. 11 There were also diagnosed patients who only presented with myalgia or fatigue, headache, and chest tightness who require additional vigilance from emergency physicians.

A history of exposure is often a reason for suspected patients to (Table 4 ). This may account for changes in the characteristics of the virus in secondary infections or potential infections. According to recent reports, SARS-CoV-2 has been detected in the tears and conjunctival secretions of diagnosed patients. 16 Since the exact infection route is still not completely understood, even if patients deny a specific exposure history, potential unknown exposure can interfere with the judgment of ED physicians.

Chest CT is considered a more accurate diagnostic tool when early clinical symptoms and exposure history are not specific. 17 A recent analysis reported that chest CT imaging has higher sensitivity for the diagnosis of COVID-19 in epidemic areas than PCR analysis of swab samples. 18 CT findings are invaluable in the clinical diagnosis of infected patients. 19 In our study, pneumonia was the most common symptom found among diagnosed patients, although it was also found in negative cases. Bilateral involvement and GGO may be the initial characteristics found in chest CT scans of diagnosed patients, consistent with a previous study where GGO was found to be the main radiological finding distributed in the lower lobes (unilaterally or bilaterally) in the initial stage, up to 4 days after onset of symptoms;

however, these characteristics were not unique for diagnosed patients. 12 under-resourced regions where rapid nucleic acid amplification tests are lacking.

The authors declare that there are no conflict of interests.

ZW and XK prepared and drafted the manuscript; XL conceived and designed the study; LH collected the data; XL, ZS, and FS read, corrected, and approved the final manuscript. All authors read and approved the final manuscript.

Please contact the author for data requests.

This study was approved by the ethics committee of the First Affiliated Hospital of USTC and Infectious Hospital of the First Affiliated Hospital of USTC. As for this research, an optout of the informed consent, the information disclosure, and an undiagnosed opportunity are guaranteed in the Ethical approval.

ORCID Wanbo Zhu http://orcid.org/0000-0003-3457-3432

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