Clinical characteristics of 57 patients infected with COVID-19 in Baodi area of Tianjin, China CURRENT STATUS: UNDER REVIEW

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide. Objective To study the clinical characteristics of COVID-19, we included 57 real-time RT-PCR confirmed patients in Baodi area of Tianjin, China, admitted to hospital from 31 January 2020 and 22 February 2020. Methods Epidemiological, demographic, clinical, and radiological features and laboratory data were analyzed. Patients were confirmed by real-time RT-PCR with pharyngeal swab and/or sputum samples. Some patients that presented positive results with sputum samples yielded negative results with multiple swab tests, suggesting sputum samples RT-PCR tests may be a more reliable means of positively diagnosing infected individuals.


Introduction
In December of 2019, a series of cases of severe pneumonia were identified in Wuhan, Hubei Province, China [1,2]. These infections were eventually found to be cases of COVID-19 (coronavirus disease 2019), which was caused by a previously uncharacterized beta coronavirus that was designated 2019-nCoV or SARS-CoV2 [3]. Symptoms of COVID-19 disease include a dry cough, fever, shortness of breath, fatigue, and lymphopenia [4]. Sequencing of the 2019-nCoV genome revealed it to be a beta coronavirus from a clade that was distinct from related members of the Orthocoronavirinae sub-family of the Coronaviridae family responsible for prior outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [5][6][7]. The 2019-nCoV virus has been shown to have a high affinity for receptors expressed on human respiratory cells and can cause severe morbidity and mortality, making it a serious ongoing global public health threat.
While the number of infected COVID-19 patients continues to rise, at present there have been only a limited number of studies published regarding clinical investigations of affected patients [8]. Prior studies have offered some insight into the clinical characteristics of this disease, as well as associated epidemiological, laboratory, and radiological findings, and treatment strategies and associated patient outcomes. Given the constantly evolving nature of this ongoing pandemic, additional studies regarding the clinical and epidemiological characteristics of pneumonia caused by 2019-nCoV are needed. In the present study, we therefore conducted a comprehensive epidemiological and clinical examination of 57 confirmed cases of 2019-nCoV pneumonia among patients admitted to Baodi Hospital in Tianjin.

Data collection
This was a retrospective study of 57 patients with confirmed cases of COVID-19 diagnosed between 31 January 2020 and 22 February 2020 in the Baodi area of Tianjin, China. In this region, specific clinics were designated to receive patients with a fever or any respiratory symptoms consistent with COVID-19 infection such as a dry cough. These clinics were additionally intended to receive any patients with a history of travel to Wuhan or the local department store (Baodi department store) where infections had been detected within two weeks prior to symptom onset. The case definitions of confirmed infections caused by the 2019-nCoV virus were based on the interim guidance of the World Health Organization (WHO) [9], and only individuals with laboratory-confirmed cases were included in the present study (n = 57). The data pertaining to these patients was collected from seven designated tertiary hospitals in the Baodi area of Tianjin. We collected data pertaining to the date of symptom onset, visits to clinical facilities, and hospital admissions. All epidemiological data had been gathered through interviews with infected patients by multiple investigators, in an effort to produce a comprehensive exposure history for each patient over the two weeks prior to symptom onset. These interviews sought to determine any times when patients were likely to have been exposed to individuals that had visited a known epicenter of this outbreak, such as Wuhan or Baodi department store.
Medical records of patients with confirmed COVID-19 disease were extracted and sent to a data collection center in Baodi for review and interpretation by doctors that had been treating COVID-19 patients. The requirement for informed consent was waived for this study due to the serious nature of this emerging pandemic and the urgent need to produce comprehensive clinical and epidemiological datasets pertaining thereto. Clinical data were collected using a standardized care form. In cases where information was unclear, the doctors responsible for the care of the patient(s) in question were contacted for clarification.

Laboratory confirmation and treatment
Upon admission, throat swab and sputum samples were collected from all patients and were tested by real-time polymerase chain reaction (RT-PCR) in order to confirm the presence of 2019-nCOV viral RNA [1]. This detection was conducted twice with >24 h between tests in order to ensure the accuracy of the resultant diagnosis.
Upon admission, all patients were subjected to a battery of laboratory tests including routine serum biochemistry, a complete blood count, and testing for the presence of other viral respiratory pathogens such as influenza A virus (H1N1, H3N2, H7N9), influenza B virus, respiratory syncytial virus, parainfluenza virus, and adenovirus. The majority of patients were administered Ribavirin (50 mg, twice per day). In addition, some patients were treated with corticosteroids (40-80 mg/day for 3-5 days) when their resting respiratory rate was greater than 30 breaths per minute, when their blood oxygen saturation was < 93% without oxygen, or when more than one pulmonary lobe exhibited > 50% disease progression upon imaging within a 48 h period. Patients also received treatment with traditional Chinese medicine and antibiotics in most cases. When patients exhibited a fever that persisted for longer than 7 days or had C-reactive protein levels > 30 mg/L (reference range: 0 -10 mg/L), they were administered quinolones and second-generation beta-lactams (oral and intravenous).

Statistical analysis
Continuous variables are given as medians with interquartile ranges (IQRs), whereas categorical variables are given as frequencies with percentages [10]. Categorical data were compared via Fisher's exact test or a chi-squared test, as appropriate, while continuous data were compared via ttests and the Mann-Whitney U test, as appropriate. P < 0.05 was the significance threshold.

Patient and public involvement
This study was a retrospective case series, and at no point in time were patients directly involved in designing the study, providing data, or influencing the interpretation of the data or the resultant manuscript.

Epidemiological characteristics
As of the 22 nd of February, 2020, 57 patients in the Baodi area had been confirmed to be infected by the 2019-nCoV virus. Of these 57 cases, three were considered mild and 54 were considered moderate in severity. As shown in Table 1, a total of 6 patients (10.5%) were < 30 years old, while 25 (43.9%) were 30-49 year old, 23 (40.3%) were 50-69 years old, and 3 (5.3%) were > 70 years old (median: 49 years, IQR: 37-64). In total, 34 patients (59.6%) were female. None of these patients had any known connection to the Wuhan where the initial spread of the 2019-nCoV virus was observed, suggesting that these were all cases of community-acquired disease. We found that 50 (87.7%) patient were associated with Tianjin Baodi department store. They were department store employees or had visited the department store, or had known interactions with above patients infected with 2019-nCoV.

Clinical features
Normal leukocyte counts (3.5-9.5×10 9 /L) were detected in the majority (49/56; 89.3%) of patients, whereas these counts were elevated or decreased in 2 (3.6%) and 5 (7.1%) patients, respectively. As shown in Table 2 Table 2). At the time of admission, chest CT findings in infected patients were unilateral or bilateral lobular or sub-segmental areas of consolidation or bilateral ground-glass opacity (Figure 1).  were treated with traditional Chinese medicine therapies, 9 (15.6%) received empirical antibiotic treatment, and 1 patient (1.8%) was administered corticosteroids.

Discussion
As of the 10 th of March, 2020, there had been over 80,000 laboratory-confirmed cases of 2019-nCoV infections in China, and this number is growing rapidly from Centers for Disease Control and Prevention of China (www.chinacdc.cn). The true number of infected patients may be even higher, either because some patients suffer from very mild disease or because the virus can have a relatively long incubation period [11,12]. As is evident from our study and other similar reports, the clinical features of early COVID-19 cases in Wuhan were distinct from cases observed in other areas of China.
In this study, 87.7% of patients were associated with a cluster of cases originating from a Baodi department store in Tianjin. None of these 57 patients reported any connection to the Huanan seafood market where the 2019-nCoV outbreak was first detected. Given that there were multiple familial clusters amid our patient cohort, our results further support the sustained human-to-human transmission of this virus.
The majority of patients in the present study from the Baodi area were female, which was consistent with prior reports in other cohorts (50.7% -73.0%) [1,4] . Patients infected with 2019-nCoV in this study ranged from 9-77 years of age [1,4,13]. We did not observe any major differences between the initial clinical symptoms of these patients relative to patients in Wuhan. However, the majority of the patients in the present study suffered from only mild-to-moderate COVID-19 disease.  [16,17].
As the majority of observed infections in the Baodi area were in patients that had no known contact with the original areas of Wuhan where this outbreak was first detected, these findings offer valuable information of the clinical and epidemiological features associated with COVID-19 disease [1]. The clinical symptoms of patients in the present study may be representative of those in patients infected with the 2019-nCoV virus in recent months. In an effort to further contain this virus and to curtail its further spread, additional quarantine protocols should be enacted and maintained. Measures that may be efficacious include banning any gatherings of >100 people and providing people accurate and upto-date information regarding the pandemic [18].

Conclusion
Relative to the symptoms that had been detected in early patients infected by the 2019-nCoV virus in Wuhan, China, we found that infected patients in the Baodi area exhibited relatively mild symptoms.
At present, there is no known efficacious treatment or vaccine that can protect against the 2019-nCoV virus. It is therefore vital that vigilant efforts to monitor for this pathogen be maintained and strengthened, quarantine protocols should be implemented and that resource be directed to ensure