COVID-19 screening-A report from a fever clinic in Shenzhen, China

Results: A total of 247 patients were quarantined pending confi rmative diagnosis. Nine had confi rmed COVID-19. Of those, all had COVID-19–related symptoms, and eight had positive epidemiological history. Chest CT scans for pneumonia were positive in seven confi rmed cases and indeterminate in two confi rmed cases. The sensitivity, specifi city, positive predictive value, and negative predictive value of the rapid screening were 100%, 93.39%, 3.64%, and 100%, respectively.


Introduction
In December 2019, a new coronavirus pneumonia occurred in Wuhan, Hubei Province, China [1][2][3]. The World Health Organization named the disease COVID-19 on February 11, 2020 [4]. At the same time, the International Committee for Virus Classifi cation named the novel coronavirus SARS-CoV-2 [5]. With the spread of COVID-19, many cases appeared in other parts of China and around the world.
Because of the effective prevention and control measures taken in China, COVID-19 is now under control in this country.
However, the situation is still serious in many other parts of the world. More than 95 million cases have been reported, and the cumulative death toll is 2,029,938 according to a report on Jan 17, 2021 [6]. were reported in Shenzhen [7]. In order to avoid nosocomial spread of COVID-19, Shekou Hospital set up a fever clinic on January 20, 2020 that remained opened 24 h to deal with patients with undiagnosed fever or respiratory symptoms or a history of exposure to COVID- 19. Any patients that presented Citation: He  within the past 14 days, or contact with an individual with fever who returned from a high-risk area within the past 14 days.
Cluster cases were defi ned as two or more cases of fever and/ or respiratory symptoms in the same family or offi ce within 14 days.

Chest CT scan
Chest CT scan was performed on all consenting adult patients using a high-resolution Light Speed VCT CT16 scanner (GE MEDICAL SYSTEMS, China), as long as there was no contraindication. The CT results were classifi ed as positive (indicating pneumonia), indeterminate (possible pneumonia), or negative (no pneumonia) for statistical purposes.

Nucleic acid testing for SARS-CoV-2
According to the national COVID-19 surveillance scheme and guidelines for laboratory detection of COVID-19 [10], throat swabs and/or nasal swabs were collected from the patients and shipped to designated laboratories for SARS-CoV-2 nucleic acid detection by Real-Time (RT)-PCR. The PCR kits were made by Da'an Company (Guangzhou, China). Two SARS-CoV-2 genes were targeted in the PCR assay: ORF 1ab and N. The sample unstable vital signs were immediately transferred to the emergency room.

Design
In this retrospective study, presenting symptoms, epidemiological data, peripheral white blood-cell count and classifi cation, chest CT scan and RT-PCR results, and other clinical data were collected from the patients' medical charts.
The primary goal of the study was to assess the reliability of a rapid screening and quarantine model based on a constellation of four parameters: Clinical symptoms, Epidemiological history, White blood-cell count and Chest CT scan results. The details of the screening process are shown in Figure 1. This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Shekou People's Hospital, Shenzhen, China.

Subjects and data collection
This report describes the screening of patients referred to the fever clinic of Shekou Hospital from January 20, 2020 to February 29, 2020. During that period, patients with COVID-19 mainly came to Shenzhen from Wuhan and nearby areas.
The fi rst case imported from a foreign country was confi rmed in Shenzhen city on March 1, 2020 [8]. The screening for COVID-19 after March 1, 2020 will be described in another paper.
The purpose of the fever clinic was to receive, screen, and quarantine patients with fever or respiratory symptoms or positive epidemiological history of COVID-19 exposure.
Patients with unstable vital signs were sent to the emergency room instead of the fever clinic. Patients that visited the fever clinic repeatedly, had incomplete clinical data, or those without SARS-CoV-2 test results were excluded from the current report.

The COVID-19 incubation period
The incubation period was defi ned as the interval between the earliest day of potential contact with the infection source (animal or person with suspected or confi rmed infection) and the fi rst day of symptoms [9]. The usual incubation period of COVID-19 is 3-7 days according to the Chinese national prevention and treatment guidelines for COVID-19 [10]. Each patient's exposure to COVID-19 was classifi ed as category 1 (<7 days since fi rst contact with the potential source), category 2 (7-14 days since fi rst contact), or category 3 (>14 days since fi rst contact; patients with an incubation period longer than 14 days were reported very early in the COVID-19 pandemic).
Confi rmed contact with infected individuals and family clustering were recorded specifi cally.

Epidemiological history
Patients meeting any one of the following criteria were defi ned as having a positive epidemiological history [ Figure 1: *Symptoms, epidemiological history, white blood cell count, nucleic acid for SARS-Coronavirus-2, chest CT scan, and other tests. †Nucleic acid should be negative at least two times for highly suspected patients before quarantine is cancelled. Regularly follow-up is still necessary for some patients at home by telephone if he /she is not ruled out thoroughly. ‡The sample must be sent to the municipal CDC for confi rmation if the fi rst laboratory result is positive.

Diagnostic criteria
The diagnostic criteria for rapid screening prior to RT-PCR testing were based on the Guidelines for the Diagnosis and Treatment of COVID-19 published by the Chinese government [10]. Fever was defi ned as a temperature of 37.

Quarantine indication
Patients were quarantined if they met any of the following conditions: positive epidemiological history and fever or respiratory symptoms; pneumonia evident on chest CT scan, especially if the white blood-cell count was within or below the normal range; the senior physician decided to quarantine the patient because of special conditions.

Statistical analysis
Descriptive statistics were used to summarize the data.

Patients with confi rmed COVID-19
Nine patients were confi rmed to have COVID-19 on although asymptomatic infection has also been reported. We therefore believe that the presence of those symptoms is the most important signal for COVID-19 screening. The United States Centers for Disease Control estimated that as many as 40% of SARS-CoV-2 infections might be asymptomatic [12]. Because asymptomatic infections can be a major source of further infections, screening based solely on presenting symptoms is not enough to control the disease, although it is important, especially in the early stage of an outbreak. We therefore screened all patients with a positive epidemiological history who visited our hospital, no matter what symptoms they presented. No confi rmed cases were found among individuals who were screened solely on the basis of a positive epidemiological history.
In the early stage of the outbreak, there were very few community infections without an epidemiological history of potential COVID-19 exposure. Hence, the survey of epidemiological history was an important step in the screening and quarantine processes used in Shenzhen. Epidemiological data were used to select individuals for chest CT scans while the available isolation rooms were allocated for quarantine. Even now, control of imported cases is one of the most important steps in stopping the spread of COVID-19 in China. Two hundred and fi fty fi ve of the 3607 patients that underwent screening in the fever clinic had a positive epidemiological history. Of the nine confi rmed cases identifi ed in the fever clinic, eight had either been in the Wuhan or Hubei province within the last 14 days or had been in contact with symptomatic patients who had been in the Wuhan or Hubei province. One confi rmed case had no defi nite epidemiological history; however, that patient had recently travelled to Shenzhen, Hong Kong, and Macau with some friends. That patient's wife was also eventually diagnosed with COVID-19. We cannot rule out the possibility that the patient was infected during the travel, although the patient's friends all tested negative for SARS-CoV-2. That case suggests that travel control might be important even if the journey does not expose the traveler to high-risk areas.
The results of chest CT scans might be the most important examination for COVID-19 screening before SARS-CoV-2 nucleic acid testing. Chest CT has a high sensitivity for COVID-19 diagnosis and can be considered a primary tool for COVID-19 detection in epidemic areas [13]. No nucleic acid testing was available in many fever clinics in the very early stage of the pandemic. Despite that, nucleic acid testing became available on January 23, 2020 in our fever clinic. Prior to that date, samples for PCR testing were sent to the local CDC lab. Chest CT scan has at least three advantages compared with SARS-CoV-2 nucleic acid testing. First, chest CT can refl ect the severity of the disease, and dynamic CT follow-ups can monitor the progress or improvement of the disease and the effectiveness of therapy. Second, CT results are available within half an hour, whereas RT-PCR testing for SARS-CoV-2 requires at least six hours. Doctors must decide how to manage each patient as soon as possible; patients in our clinic with any quarantine indications were sent to an isolation room, while those without quarantine indications were either sent home or hospitalized according to the common rule. Third, there have been many reports of false-negative results of SARS-CoV-2 nucleic acid testing. However, chest CT can reveal pulmonary abnormalities consistent with COVID-19 in patients with negative RT-PCR results [14,15]. The characteristics of COVID-19 on CT scans have been reported [16,17]. The typical fi ndings include ground-glass opacifi cation and multiple bilateral patchy shadowing, although some patients only show ground-glass nodules [18,19]. RT-PCR for SARS-COV-2 247 tested; 9 positive *Pulmonary basic diseases include chronic obstructive emphysema, bronchiectasis, lung cancer, pulmonary tuberculosis, and bronchial asthma. †Non-pulmonary basic diseases include diabetes, hypertension, coronary heart disease, hyperlipidemia, and fatty liver    It is very diffi cult to make a differential diagnosis in such cases. We performed routine blood examinations at the same time as the chest CT scans. Patients were isolated for quarantine if the CT scan showed pneumonia and the white blood-cell count was normal or low. Patients with those characteristics and a positive epidemiological history should be highly suspected to have COVID-19. In Shenzhen, CT scans to detect COVID-19 were free in the early stage of the pandemic.
In later stages, patients without health insurance paid about $60 for the CT scan. Some patients might refute chest CT scan because of the cost.
Peripheral white blood-cell count is also an important factor in the screening and differential diagnosis of COVID-19. showed a high white blood-cell count. Lymphocytopenia is another feature of COVID-19, according to previous reports [9,20]. Three of the confi rmed cases identifi ed in the fever clinic showed lymphocytopenia.
We performed screening tests based on epidemiological history, clinical characteristics, white blood-cell count, and chest CT scan. All of those data can be obtained within one hour.
Decisions about which patients to quarantine had to be made as quickly as possible. However, RT-PCR is time consuming. We used positive RT-PCR results from the municipal CDC lab as the gold standard to confi rm diagnoses of COVID-19. Based on that standard, the sensitivity and negative predictive value of the multifactor rapid screening used in the fever clinic were both 100%, which was important for early diagnosis and isolation.
The positive predictive value was only 3.60% which is to say that more than 30 patients had to be quarantined in order to fi nd one patient with COVID-19. The low positive predictive value resulted in a large burden on manpower, materials, and fi nances, but was necessary in order to have enough sensitivity and specifi city to effectively contain the spread of the disease.
Therefore, the government must attach great importance to the implementation of screening procedures to contain the spread of COVID-19 despite the high costs.  Figure 3.

Conclusion
The experiences in a fever clinic Shenzhen, China showed that rapid COVID-19 screening was possible and reliable, although the burden was great, requiring substantial manpower, materials, and fi nancial support from the government and the Pulmonary infl ammation on chest CT 7 Possible changes in infl ammatory lesions on chest CT 2 Positive RT-PCR test 9 Displayed novel coronavirus antibodies 0 *Pulmonary basic diseases include chronic obstructive emphysema, bonchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma. †Non-pulmonary basic diseases include diabetes, hypertension, coronary heart disease, hyperlipidemia, and fatty liver

Acknowledgments
We thank President Xudong Luo, Yanwei Chen and the whole staff for their jobs in COVID-19 prevention and control.
We also thank the members of Information Department for their assistance in providing accurate data. This work was supported by Nanshan District government without a specifi c funding number.

Disclaimer
The opinions expressed by authors contributing to this journal do not necessarily refl ect the opinions of the Centers for Disease Control and Prevention or the institutions with which the authors are affi liated.

Contribution of the authors
All listed authors have made substantive intellectual contributions to this article.

Highlights
Patients with fever, respiratory symptoms, or an epidemiological history of contact with COVID-19 were screened in a fever clinic.
The quarantine model was based on a constellation of four parameters: clinical symptoms, epidemiological history, white blood-cell count, and chest CT scan results.
Rapid COVID-19 screening was possible and reliable, although the burden was great, requiring substantial manpower,