Comparative study on the clinical characteristics of local cases of COVID-19 and imported cases from abroad

Abstract It is presently unknown whether imported cases of the 2019 coronavirus disease (COVID-19) have different characteristics when compared with local cases. To compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad. This was a retrospective study of confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29th, 2020, and March 27th, 2020. The clinical characteristics of the patients were compared between local and imported cases. Compared with local cases, the imported cases were younger (27.3 ± 11.7 vs. 43.6 ± 22.2 years, P < .001), had a shorter interval from disease onset to admission (1.0 (0.0–2.0) vs 4.0 (2.0–7.0) days, P < .001), lower frequencies of case contact (17.4% vs 94.1%, P < .001), fever (39.1% vs 82.4%, P < .001), cough (33.3% vs 51.0%, P = .03), dyspnea (1.9% vs 11.8%, P = .01), fatigue (7.5% vs. 27.5%, P = 0.001), muscle ache (4.7% vs. 25.5%, P < 0.001), and comorbidities (P < .05). The imported cases were less severe than the local cases, with 40.4% versus 5.9% mild cases, 2.8% versus 15.7% severe cases, and no critical cases (P < .001). The length of hospital stay was longer in imported cases than in local cases (32.3 ± 14.5 vs 21.7 ± 11.2 days, P < .001). The imported cases showed smaller biochemical perturbations than the local cases. More imported cases had no sign of pneumonia at computed tomography (45.0% vs 14.9%, P = .001), and none had pleural effusion (0% vs 14.9%, P < .001). Compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.


Introduction
The 2019 coronavirus disease (COVID-19) is a global pandemic of acute respiratory distress syndrome (ARDS) caused by a novel coronavirus (SARS-CoV-2). [1,2] SARS-CoV-2 is a member of beta genus coronaviruses closely related to SARS-CoV. [3] The Imported cases refer to patients who caught COVID-19 in other countries than their country of residence, that is, including visitors from other countries and local resident returning home after being infected abroad. This is opposite to local cases, which refer to individuals who caught COVID-19 in their country of residency. It is presently unknown whether imported cases have different characteristics when compared with local cases. One study from Singapore reported that imported cases were identified more quickly. [17] This might be an important issue for the management of the disease, especially in the context of a progressive end to confinement in many geographical areas. In addition, the imported, unlinked, and asymptomatic cases could be an important source of secondary contagion and amplification of transmission during confinement. [17] Therefore, the aim of the present study was to compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad.

Study design and patients
In this retrospective study, we investigated the confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29 th , 2020, and March 27 th , 2020. All patients were confirmed of COVID-19 according to the WHO interim guidance. [19] According to the source of the cases, all patients were divided into 2 groups: local cases and imported cases from abroad.
The study was approved by the Ethics Committee of Beijing Ditan Hospital affiliated with Capital Medical University. This article was a retrospective analysis, and the Committee waived the need for individual consent.

Laboratory tests
All suspected patients were admitted to quarantined observation rooms in the emergency department. A nucleic acid amplification test was performed on swab specimens from all patients with suspected disease at admission. [19] The patients with a positive diagnosis were admitted to the hospital, whereas patients with an initial negative result were kept in quarantine and underwent a second nucleic acid test after 24 hours; of these, patients with a second negative result on the nucleic acid test were considered to not have an infection and were discharged from the hospital.
All confirmed cases underwent a blood gas analysis from arterial blood sampled from the radial artery by a physician. The electrode method was used for blood gas analysis on a Cobas B221 blood gas analyzer (Roche Diagnostics, Basel, Switzerland). Peripheral venous blood was also sampled routinely for the analysis of CD4 + and CD8 + peripheral blood mononuclear cells on a FACSCanto II flow cytometry system (BD Diagnostics, Sparks, MD). Pulmonary lesions were examined using a 16-row emotion computed tomography scanner (Siemens, Erlangen, Germany).

Data collection
Age, sex, complications (diabetes, liver diseases, high blood pressure, heart diseases, tumors, renal insufficiency, cerebrovascular diseases, rheumatic autoimmune diseases, lung diseases, and blood system diseases), the time from disease onset to admission, the time from visit to the first positive nucleic acid test, body temperature at admission (the body temperature measured by the physician in our hospital for the first time), close contact history (whether there was any history of contact with confirmed or suspected patients), clinical symptoms (fever (body temperature ≥37.3°C), cough, sore throat, headache, dyspnea, fatigue, muscle aches, and diarrhea), and clinical typing (based on the "Diagnosis and Treatment Program for Novel Coronavirus Pneumonia (Seventh Edition)" issued by the National Health Commission. [20]

Statistical analysis
The Kolmogorov-Smirnov test was used to confirm whether the continuous variable conformed to the normal distribution. The continuous variables conforming to the normal distribution were described as means ± standard deviations and were analyzed using the independent sample t test. The continuous variables that did not conform to the normal distribution were described as medians (interquartile ranges) and analyzed using the Mann-Whitney U test. The categorical data were described as numbers (percentages) and analyzed using the x 2 test or Fisher exact probability test, as appropriate. SPSS 22.0 (IBM, Armonk, NY) was used for all analyses. Two-sided (except for the x 2 test) P values <.05 were considered statistically significant.

Discussion
It is presently unknown whether imported cases of COVID-19 have different characteristics when compared with local cases. Therefore, this study aimed to compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad. The results suggest that compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.
In the present study, the imported cases were admitted to the hospital earlier after symptom onset than the local cases. This phenomenon was also observed in Singapore, where the screening protocols are highly efficient. [16,17] Since the present study examined patients mainly admitted in March, that is, well after the start of the pandemic and the implementation of sanitary measures, this could denote that patients coming back from travel might be more aware than locals of the possibilities of COVID-19 transmission and could consult earlier after symptom onset, as instructed by public health authorities. In addition, most of them would be in quarantine and aware of the necessity of reporting symptoms. A meta-analysis observed that higher disease Table 1 Characteristics of the patients.

Variables
Total (n = 160) Imported cases from abroad (n = 109) Local cases (n = 51) P awareness could lead to a milder presentation. [21] The knowledge about red flag symptoms, which is provided to anyone entering quarantine for COVID-19 prevention, results in better management. [22] Many patients were asymptomatic or presymptomatic at admission, as supported by a study reporting 31% to 56% of such patients. [23][24][25][26] This resulted, at presentation, in milder disease, fewer biochemical abnormalities, and fewer imaging abnormalities compared with local cases. Because of border surveillance and mandatory testing, the patients can be identified many days before the onset of symptoms, whereas many local cases are tested when the symptoms appear. Therefore, many patients who would be asymptomatic or with non-specific mild symptoms were hospitalized. In addition, because all inbound individuals are told to check for specific symptoms, they might consult earlier than local patients. Although the imported cases are milder, an earlier discovery leads to longer hospitalization since they can be discharged after there is no risk of virus transmission, as for local cases. Supporting this, 2 imported cases had to be admitted to the ICU during hospitalization. Of note, none among the 160 patients required mechanical ventilation or died. This is a better prognosis than what is reported in the literature. Indeed, a study reported an overall in-hospital mortality of 15% to 20%, with up to 40% requiring admission to the ICU. [2] On the other hand, a cohort study showed that the overall mortality to COVID-19 was 2.3% in China, but with higher mortality rates in the older age groups. [7] The good prognosis observed in the present study could be because the patients were relatively young (32.5 ± 17.5 years overall). In addition, the imported cases were younger than the local cases. Table 3 Imaging examinations.

Variables
All (n = 160) Imported cases from abroad (n = 109) Local cases (n = 51) P   The imported cases were more likely to be workers or students, that is, individuals in the active population, whereas the local cases could cover the whole range of the local population. Still, it is only a hypothesis because the actual age of all people who crossed the border during the study period is unknown and cannot be compared to the age of the local population. Nevertheless, the local cases had higher frequencies of comorbidities (diabetes, heart diseases, hypertension, and lung diseases) known to negatively influence the disease outcomes, [10][11][12]27] but they nevertheless did not fare worse. This study has limitations. It was a retrospective study in a small sample of patients from a single hospital. Only the characteristics at admission were examined. In addition, because of the retrospective nature of the study, only the data that were routinely measured and recorded in the charts could be analyzed. Additional studies are still necessary to refine the results of the present study.
In conclusion, the results suggest that compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs, possibly because of mandatory testing and higher awareness of symptoms. Those results suggest a higher surveillance and/or disease awareness in patients who might have been infected abroad.