key: cord-337324-jxtch47t
authors: Qian, Guo-Qing; Yang, Nai-Bin; Ding, Feng; Ma, Ada Hoi Yan; Wang, Zong-Yi; Shen, Yue-Fei; Shi, Chun-Wei; Lian, Xiang; Chu, Jin-Guo; Chen, Lei; Wang, Zhi-Yu; Ren, Da-Wei; Li, Guo-Xiang; Chen, Xue-Qin; Shen, Hua-Jiang; Chen, Xiao-Min
title: Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series
date: 2020-02-25
journal: nan
DOI: 10.1101/2020.02.23.20026856
sha: 
doc_id: 337324
cord_uid: jxtch47t

Background Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei. Aim To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China. Design Retrospective case series. Methods 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. Results Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia. Conclusions Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.

Coronavirus disease 2019 (COVID-19) is highly contagious and spreads rapidly through human-to-human transmissions. 5, 6 As of 20 February, 75 571 confirmed cases had been reported in Mainland China and 1083 confirmed cases in 24 other countries and regions. Amongst the cases in Mainland China, 2239 cases died, 11 cases of death was reported from out of Mainland China. 7 There were 41 initial cases of COVID-19 that were directly or indirectly linked to the Wuhan Huanan Seafood Wholesale Market, as reported by Huang and colleagues. 8 The clinical features include fever, dry cough, dyspnea, myalgia, fatigue, decreased leukocyte counts and computed tomography (CT) evidence of pneumonia. 8 Subsequently, Chen and colleagues reported 99 cases from a single centre of Wuhan, but the severe and non-severe cases were not compared. 9 And then Wang and colleagues published a study based on 138 hospitalized patients from Wuhan. 10 However, all these studies are based on cases identified in Wuhan. Recently, Guan and colleagues reported 1099 cases with laboratory-confirmed SARS-CoV-2 from 552 hospitals across 31 provinces/provincial municipalities. 11 They reported that the median age was 47.0 years, 41.90% were females, 31.30% had been to Wuhan and 71.80% had contacted people from Wuhan, and the average incubation period was 3.0 days. The most common symptoms were fever and cough. 11 Together, several articles about cases from Wuhan have reported epidemiologic and clinical manifestations and provided important initial background upon which we seek to furnish further in this paper. [8] [9] [10] 12 The clinical features of COVID-19 of cases outside Wuhan is still largely unknown.

Zhejiang Province has consistently been one of the top three provinces with most cases in China and therefore provide a good basis to learn how COVID-19 spreads outside Wuhan. The cluster events, public transport transmissions, and clinical diagnosis of this new infectious disease are of great importance to be reported as it shred lights on of cases that occur outside Wuhan. Here, we report the epidemiologic and clinical characteristics of COVID-19 patients from five hospitals in Zhejiang province, China.

We performed a retrospective, multicentre study on the epidemiologic history, clinical records, laboratory results, and chest radiological features of 88 laboratory-confirmed and 3 clinical-diagnosed patients with COVID-19 that were diagnosed from 20 January 2020 to 11 February 2020. Final follow-up for this report lasted until 16 February 2020.

The primary method of diagnosis is to perform real-time reversetranscriptase polymerase-chain-reaction (RT-PCR) assay test using throat swab specimens that were collected from upper respiratory tracts. This test is done twice at 24-hour interval. Of the 91 cases reported in here, 88 cases were tested positive for SARS-CoV-2 at least once. These laboratory confirmation assays for SARS-CoV-2 were performed at CDCs of various cities and at Ningbo First Hospital following the standard protocol. 8 Three further cases were reported in Ningbo cohort as clinical-diagnosed COVID-19 pneumonia because of their epidemiological history, signs, symptoms and chest CT evidence according to National Health Commission of the People's Republic of China guidance, though they tested negative for the SARS-CoV-2. 13,14 The incubation period was defined as the time from the exposure to the confirmed or suspected transmission source to the onset of illness.

A team of doctors who had been treating these patients extracted the medical records of these patients and sent the data to working group in Ningbo to further examine. When the data were not clear or missing, the working group in Ningbo would clarify the details with the doctors in charge of treating these patients. The study has been reviewed and approved by the Medical Ethical Committees (2020-R018). The requirement for written informed consent was waived because of the urgent need to collect clinical data and no harm could potentially be done to patients. Doctors who treated the patients collected and recorded the epidemiological characteristics by interviewing each patient on their activity history during the two weeks before symptoms onset or admission into hospital. All patients underwent chest CT scans. The clinical symptoms, chest CT and laboratory findings on admission were extracted from electronic medical records. Laboratory results included blood routine, blood chemistry, arterial blood gas, fibrinogen, liver and renal function, electrolytes, C-reactive protein, and procalcitonin.

Patients were divided into the diagnosed as severe group and mild group according to national treatment guideline. 13,14 Questionnaires of MuLBSTA scores 15 were recorded by attending physicians according to six indexes, which are multilobular infiltration, lymphopenia, bacterial co-infection, smoking history, hypertension, and age. All data were checked by two experienced physicians (GQ and NY).

We present the summary statistics of continuous variables using the means and standard deviations (SD) or median (IQR), comparison across groups were performed using the Mann-Whitney U test. Categorical variables were expressed as the counts and percentages in each category. Chi-square tests was used for categorical variables as appropriate. All analyses were analyzed by IBM SPSS statistics version 26.0.

This was a retrospective case series study, no patients and public were involved in the design, or conduct, or reporting, or dissemination plans of our research.

Of all 91 patients recruited as of 11 February, we detected 88 (96.70%) laboratory-confirmed COVID-19 pneumonia with throat swab samples that positive for SARS-CoV-2 and 3(3.30%) clinical-confirmed COVID-19 pneumonia since they had definite demographic history, typical symptoms and chest CT images.

As shown in Table 1 , The median age of the 91 patients was 50 years (IQR, 36.5 to 57.0), ranged from 5 to 96 years. There was 1 child (5 years . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . old), 1 student who were 17-years of age, and six cases of elderly patients aged 70 or above. Adults account for most of the cases, with breakdown as follows: aged 18-39 (26 cases, 28.57%), aged 40-49 (16 cases, 17.58%), aged 50-59 (28 cases, 30.77%) and aged 60-69 (13 cases, 14.29%). There were 54 female patients (59.34%), with none of them pregnant.

As for epidemiologic characteristics, 31 patients had been to Wuhan/Hubei within the past two weeks (G0). Local cases are defined as follows: 8 patients had within the past two weeks had contact with personnel who had been in Wuhan/Hubei, these are the first generation of local cases (G1). Following that 40 patients contracted the disease after having had contact with the local cases, these are defined as G2 local cases. In particular 23 of the G2 cases were all derived from an event where people collectively prayed for good luck in a temple for the new lunar year. There were 11 patients who were infected while air travelling. It is impossible to establish how the remaining 1 patient contracted the disease. None of the patients had a history of exposure to the Huanan seafood wholesale market. No healthcare workers were found in our study. Moreover, none of the health workforce in 

On admission, the most common symptoms were fever (65, 71.43%), cough (55, 60.44%) and fatigue (40, 43.96%) ( Table 2 ). Among them, 34 (37.36%) cases have temperature between 38.1-39℃, but none had a very high fever (body temperature > 41℃). Other symptoms included expectoration (30, 32.97%), anorexia (23, 25.27%), diarrhea (21, 23.08%), neausea (11, 12 .09%) and vomiting (6, 6.59%). In a case, her abdominal discomfort was the only symptom. Nine patients were diagnosed as severe pneumonia because of the development of pneumonia. As of 16 February, 60 (65.93%) patients were still isolated in our hospitals, and 31 (34.07%) patients had been discharged and no patients had died so far. The median of incubation period is 6 (IQR, 3-8) days, and number of days from first visit to a doctor till the case is confirmed is 1 (1-2).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint According to data of laboratory tests, half of patients (49, 53.85%) demonstrated elevated levels of C-reactive protein (CRP), but elevated levels of procalcitonin were detected in only a minority (14, 15.39%). Data from blood routine showed that 14 (15.39%) patients had below the normal range of leucocyte, and 3 (3.97%) cases with elevated levels ( Table 3) The serum level of albumin was suppressed in 43 (47.25%) patients. ALT (7, 7.69%) and AST (9, 9.89%) were slightly elevated in minority of cases. Suppressed calcium concentration and serum sodium concentration were less common. Some patients had abnormality in arterial blood gas analysis, with decreased PaO2 in 18 cases, increased levels of lactic acid in 25 cases, and increased PH in 14 cases.

Our study has stratified patients with COVID-19 pneumonia based on the severity of symptoms on admission according to national guidelines. 13, 14 Nine patients were diagnosed as severe pneumonia because of the development of pneumonia. Compared with those mild patients, patients diagnosed as severe pneumonia had numerous differences in laboratory results (Table 4) , including higher neutrophil, lower lymphocytes count, hyponatremia, hypocalcemia, as well as higher levels of CRP. MuLBSTA score is used to predict mortality in viral pneumonia, amongst the 9 severe pneumonia patients their MuLBSTA scores were significantly higher, indicating they had higher mortality risks.

This report, to our knowledge, is the largest case study to date of hospitalized patients with COVID-19 in Zhejiang province, which is outwith of Wuhan and Hubei. As of 16 February, 2020, of the 91 cases in the present study, 9 were diagnosed as severe pneumonia, 31 were discharged, 60 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint The most common symptoms at the onset of COIVD-19 were fever, cough, and fatigue. The median of incubation period was 6 (IQR, [3] [4] [5] [6] [7] [8] days and from first visit to a doctor to confirmed diagnosis was only 1 (1-2) days.

Our study provided further evidence that rapid human-to-human transmission of SARS-CoV-2 outside Wuhan had occurred. None of the patient in this study had direct contact with wildlife or from Huanan Seafood Wholesale Market. While 8.79% had contact with people who had travelled from Wuhan, more than 52.75% were local Zhejiang residents with no travel history to Wuhan and Hubei. In particular, 23 cases of 38 cases of Ningbo Cohort were related to the outbreak of a temple cluster, including 11 patients had directly participated in a temple activity. Our findings have provided strong evidence that large social events should be cancelled in order to prevent infection.

Notably, there is 54 (59.34%) female cases in our study compared to 27% of the first reported study 8 or 41.8% of a recently study 11 , and 44% of a recently study from Zhejiang Province. 16 However, it has been found that more males were infected by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV. 17, 18 Whether it is related to endocrinology 9 , social activities, or religious activities still needs further research. Fever (71.43%), cough (60.44%) and fatigue (43.96%) are the most comment clinical characteristics in our study and is similarly to the cohorts reported in the published literature. 8, 10, 16 Furthermore, it is reported only 43.8% of COVID-19 had fever onset and 87.9% reported having had fever during hospitalization. 11 Fever is less widespread amongst those infected with COVID-19 than those with SARS-CoV (99%) and MERS-CoV (98%). 19 As screening heavily on fever detection, patients that do not have fever might get suspected as being wrongly diagnosed.

Some COVID-19 cases had atypical symptoms or were asymptomatic. Furthermore, asymptomatic persons are potential sources of SARS-CoV-2 transmission. 20 It appears that transmission is possible during the incubation period, and the carrier cannot be spotted. 20 Recently, a study reported that they detected SARS-CoV-2 in stool samples from patients with abdominal symptoms. 21 Interestingly, we had detected SARS-CoV-2 in rectal swab of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . https://doi.org/10.1101/2020.02.23.20026856 doi: medRxiv preprint patients who were twice tested negative by throat swab specimens using RT-PCR. Therefore, it is helpful to detect atypical symptoms COVID-19 using both throat swab and rectal swab, particularly for patients who suffer symptoms with their digestive tract, like diarrhea.

Only 28 (30.77%) cases had lymphopenia in our study, while half the patients (49, 53.85%) demonstrated elevated levels of C-reactive protein, decreased platelet in 10 cases. Most cases had normal serum levels of procalcitonin on admission (procalcitonin <0.04 ng/ml), except 14 cases had procalcitonin level higher than 0.04 ng/ml. All patients were scanned by chest CT scan. Of the 91 patients, 61 (67.03%) had multilobe infiltration. The typical manifestation of lung CT were ground-glass opacification (GGO) of bilateral multiple lobular and subsegmental areas of consolidation (Figures 1 and 2 ).

Our study provided three cases as clinical-confirmed COVID-19 pneumonia because of their epidemiological history, signs, symptoms and chest CT evidence according to guidance, though they tested negative for the SARS-CoV-2. Thus, CT could be used as an important differential method in cities where they are lacking nucleic acid kits, like Wuhan, and help to bring forward the isolation period for the infected.

Currently, no anti-viral agents have been proven to be effective treatment for COVID-19. It is reported that combination of Lopinavir and Ritonavir had been applied to SARS-CoV-2 patients with substantial clinical benefit. 22 As an emerging virus, all the patients received anti-viral agents in Ningbo cohort, including Kaletra (Lopinavir/Ritonavir) and Umifenovir, 9 cases received methylprednisolone to treat high fever, SpO2 ≤93% and hypoxiemia. The dose of methylprednisolone depends on disease severity between 1mg/kg to 2mg/kg. However, the outcome is still unclear.

As of 16 February 2020, no death has been reported in Zhejiang province as the government authority has taken unprecedented and effective effort to reduce the risk of transmission. Early diagnosis, early isolation and early management all contributed to reducing transmission and mortality in Zhejiang. However, 60 patients are still hospitalization and their cases should be followed up in the future.

Our study has some limitations. Firstly, two thirds of patients are still hospitalized. For those who had been released their cases are being followed up for 2 weeks, and further information can be learnt from these individuals.

Secondly, we just have recruited 91 cases. Increasing the number of cases is good for observing COVID-19 outside of Wuhan/Hubei. Thirdly, we did not . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . https://doi.org/10.1101/2020.02.23.20026856 doi: medRxiv preprint have many severe cases to compare the differences of epidemiological and clinical features. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.23.20026856 doi: medRxiv preprint 

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This work was supported by Natural Science Foundation of Zhejiang Province (Q17H010001), Natural Science Foundation of Ningbo (2017A610246), and Shaoxing Municipal Science and Technology Plan Project.

This article has been accepted for publication in QJM: An International Journal of Medicine, published by Oxford University Press.