Epidemiological and clinical features of imported and local patients with coronavirus disease 2019 (COVID-19) in Hainan, China

doi:10.21203/rs.3.rs-39645/v2

Background: Hainan Island, which is a popular tourist destination, received many imported cases of Coronavirus disease 2019 (COVID-19) but successfully contained the epidemic within one month. We described the epidemiological and clinical characteristics of COVID-19 in Hainan and compared these features between imported and local cases to provide information for other international epidemic areas.

Methods: We included 91 patients (56 imported and 35 local cases) from two designated hospitals for COVID-19 in Haikou, China, from January 20 to February 19, 2020. Data on the demographic, epidemiological, clinical and laboratory characteristics were extracted from medical records. Patients were followed until April 21, 2020, and the levels of antibodies at the follow-ups were also analyzed.

Results: Of the 91 patients, 78 (85.7%) patients were diagnosed within the first three weeks after the first case was identified (Day 1: Jan 22, 2020), while the number of local cases started to increase during the third week. No new cases occurred after Day 29. Fever and cough were two main clinical manifestations. In total, 15 (16.5%) patients were severe, 14 (15.4%) had complicated infections, nine (9.9%) were admitted to the ICU, and three died. The median duration of viral shedding in feces was longer than that in nasopharyngeal swabs (19 days vs 16 days, P=0.007). Compared with local cases, imported cases were older and had a higher incidence of fever and concurrent infections. There was no difference in outcomes between the two groups. IgG was positive in 92.8% patients (77/83) in the follow-up at week 2 after discharge, while 88.4% patients (38/43) had a reduction in IgG levels in the follow-up at week 4 after discharge, and the median level was lower than that in the follow-up at week 2 (10.95 S/CO vs 15.02 S/CO, P<0.001).

Conclusion: Imported cases were more severe than local cases but had similar prognoses. The level of IgG antibodies declined from week 6 to week 8 after onset. The short epidemic period in Hainan suggests that the epidemic could be quickly brought under control if proper timely measures were taken.

Infectious Diseases

coronavirus disease 2019

severe acute respiratory syndrome-related coronavirus 2

epidemiology

clinical features

prevention and control

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by lung damage, was first reported in Wuhan, China, in December 2019 [1,2]. By August 21, 2020, it had spread to 213 countries worldwide, causing 22856134 cases and 796992 deaths, with a crude mortality of 3.4% [3]. Although COVID-19 is likely a zoonotic disease, it can be transmitted from person to person [4,5], with a reproductive number of 1.5-4 [6,7]. COVID-19 is mainly transmitted by contact and droplets but can also be transmitted through the digestive tract and conjunctiva [8,9]. At present, the numbers of COVID-19 cases in USA, Brazil and other countries are increasing rapidly, and many are locally incident cases [3]. As is known, the containment of epidemics at the early stage is the most critical, effective and efficient before the outbreak goes out of control. Although many countries once contained the spread of the epidemic, new imported cases are now emerging again. The prevention and control of the epidemic still faces great challenges.

Hainan Province is a popular domestic and international tourist destination with 9.34 million permanent residents. During the spring festival holiday, many people, including those from Wuhan and its surrounding areas, choose to spend their vacations on Hainan Island. According to the statistics, from December 30, 2019, to January 22, 2020, which was the day before Wuhan was locked down, approximately 74,600 tourists had travelled from Wuhan to Hainan by plane [10], and the first case of COVID-19 in Hainan was reported on January 22, 2020 (Day 1). Compared with other regions except Wuhan, Hainan Province was under greater pressure to prevent and control the epidemic. However, the last confirmed patient in Hainan was reported on February 19, 2020 (Day 29) (Figure 1) [11]. The relatively short epidemics period is largely attributable to the strict isolation and prevention measures implemented from top to bottom throughout the country, and it also implies that the measures that Hainan adopted to contain the epidemic were timely and successful. Thus, Hainan’s experience may have important implications for other international epidemic areas.

This study describes the epidemiological and clinical characteristics of COVID-19 in Hainan, as well as the government's prevention and control measures, and compares these features between imported and local cases, which may provide an instructive example for countries and regions that are vulnerable to upcoming epidemics.

Study design and participants

We retrospectively included all patients with COVID-19 in Hainan General hospital and The Second Affiliated Hospital of Hainan Medical University from January 22 to February 19, 2020. These two hospitals were designated hospitals for treating adult patients in Haikou, the capital city of Hainan Province. Patients were followed until April 21, 2020, when the last discharged patient had been followed for four weeks. This study was approved by the Ethics Committee of Hainan General Hospital and The Second Affiliated Hospital of Hainan Medical University (HN-2020-31), and oral consent was obtained from all patients. All patients with COVID-19 enrolled in this study were diagnosed according to the WHO interim guidance [12] and were divided into an imported case group and a local case group according to epidemiological data.

Definitions

Imported cases were defined as the patients who came from a COVID-19 epidemic area (Hubei Province) within 14 days or from a COVID-19 epidemic area and could not trace the source of infection. The local cases were defined as the patients who stayed in the locality for more than 14 days before onset and had not gone to an epidemic area. If two or more confirmed cases were found concurrently and there was the possibility of human-to-human transmission due to close contact or infection through co-exposure, then the case is determined as a clustered case [13,14]. Fever was defined as an axillary temperature of at least 37.3°C. Acute respiratory distress syndrome (ARDS) was defined according to the Berlin definition [15]. We defined the degree of severity of COVID-19 (severe vs. mild) at the time of admission using the American Thoracic Society guidelines for community-acquired pneumonia [16].

Data collection

The epidemiological characteristics (including the residence, whether the patient was from the epidemic area, recent exposure history, etc.), clinical symptoms and signs, laboratory data, chest computed tomography (CT) findings, SARS-CoV-2 RNA, IgM antibody and IgG antibody against SARS-CoV-2 were extracted from electronic medical records.

Laboratory confirmation of SARS-CoV-2 infection

SARS-Cov-2 RNA testing was performed by the hospital’s laboratory and the key laboratory of Hainan Centre for Disease Control and Prevention (CDC), China, by real-time RT-PCR according to the Chinese national CDC recommended protocol. The nasopharyngeal swab and feces were collected every 2-7 days during hospitalization and twice every 7 days during follow-up for discharged cases. Then, the RNA samples from the nasal swab and feces specimens were extracted and subjected to real-time RT-PCR testing using SARS-CoV-2-specific primers and probes. Specifically, the primers for the open reading frame 1ab (ORF1ab) were 5’-CCCTGTGGGTTTTACACTTAA-3’(Forward) and 5’-ACGATTGTGCATCAGCTGA-3’(Reverse), and the corresponding probe was 5’-CY3-CCGTCTGCGGTATGTGGAAAGGTTATGG-BHQ1-3’. Primers for the nucleocapsid protein (N) were 5’-GGGGAACTTCTCCTGCTAGAAT-3’ (Forward) and 5’-CAGACATTTTGCTCTCAAGCTG-3’ (Reverse), and the corresponding probe was 5’-FAM-TTGCTGCTGCTTGACAGATT-TAMRA-3’. The duration of SARS-CoV-2 shedding was defined as the time from symptom onset to the first negative SARS-CoV-2 RNA test after the last SARS-CoV-2 RNA positive test during the follow-up.

Antibody measurement

IgM and IgG antibodies against SARS-CoV-2 in the plasma samples were tested using the Diagnostic Kit for Novel Coronavirus (2019-nCOV) IgM/IgG Antibody (Magnetic particle CLIA) supplied by Bioscience (ChongQing) Diagnostic Technology Co. according to the manufacturer’s instructions.

Statistical Analysis

Continuous variables were expressed as the mean (SD) or median (IQR) and compared by the t-test or Mann-Whitney U test. Categorical variables were expressed as the frequency (%) and compared by the χ² test or Fisher’s exact test between the imported cases and local cases. For the laboratory indicators, we categorized the results as normal or abnormal (increased or decreased). IgG levels during the follow-up were compared using the Wilcoxon matched-pairs signed ranks test. We used SPSS (IBM, version 26.0) for all analyses.

Demographics and epidemiological characteristics

All 91 patients with confirmed COVID-19 in Hainan General Hospital (n=69) and The Second Affiliated Hospital of Hainan Medical university (n=22) were enrolled. Of the 91 patients, 56 were imported and 35 were local patients. The mean age was 50 years, and 57.1% were men. This outbreak lasted one month from the first patient admittance on Jan 20, 2020, to the last patient on Feb 19, 2020 (Figure 1). Of these patients, 78 were admitted within the first three weeks after the first case was identified, 88.6% (31/35) of local patients were admitted by day 14, and these statistics were similar to the overall patient statistics in Hainan Province. Of all 168 patients, 142 new cases were confirmed before day 21, and 52 local patients were diagnosed after day 14 (Figure 1). Among 56 imported patients in two hospitals, 53 (94.6%) came from the epidemic center, Wuhan City and its surrounding area. The median interval period between leaving the epidemic center to symptom onset in 53 patients was five days (IQR 2-12, range 1-34). Overall, 42 (46.2%) patients had a history of contact with confirmed COVID-19 patients, with a median interval before onset of eight days (IQR 4-13, range 1-22). Compared to imported patients, the local patients were significantly younger (mean age, 46 years vs. 52 years; P=0.03), more likely to occur in cluster outbreaks (77.1% vs. 46.4%, P=0.004), and had close contact with COVID-19 patients (68.6% vs. 32.1%, P=0.001) (Table 1).

Clinical characteristics and complications

The most common symptoms at the onset of illness were fever (79.1%), dry cough (79.1%), expectoration (39.6%), fatigue (38.5%), and shortness of breath (29.7%), while diarrhea (14.3%) and nausea and vomiting (7.7%) were not rare. In total, 87 (95.6%) patients had more than one sign or symptom, and 23 patients had combined fever, cough, and shortness of breath. Only four (4.4%) cases had no symptoms. The median highest temperature was 38.0°C, and the median duration of fever was eight days. Nine (9.9%) patients were admitted and transferred to the ICU because of the ARDS and organ dysfunction. The median durations from the first symptoms to hospital admission and ARDS were 5 days (IQR, 3-9) and 8 days (IQR, 6-10), respectively.

Clinically, patients were diagnosed as mild (76 cases, 83.5%) or severe (15 cases, 16.5%) cases. The fifteen severe patients included 3 local and 12 imported cases. Among these severe patients, 14 had complicated bacterial infections, 9 had septic shock, 13 had ARDS, 6 had multiple organ dysfunction syndrome (MODS), and 3 patients died. Compared with local patients, imported patients had a higher prevalence of fever (P=0.001), a higher peak temperature (P=0.028), and more complicated infections (P=0.043) and tended to be more severe (21.4% vs 8.6%) (Table 2).

Laboratory examination and imaging findings of patients with COVID-19

Of the 91 patients, 21(23.1%) had a white cell count of less than 4.0×10⁹/L, and 39 (42.9%) had a lymphocyte count of less than 1.1×10⁹/L. The blood lymphocyte count, platelet count and serum albumin of the imported cases were significantly lower, while the levels of blood creatine kinase and CRP were significantly higher than those in local patients (all P<0.05). All the patients had abnormality in chest CT scans, 79 (86.8%) patients’ lesions were located at the lung periphery, and 75 (82.4%) showed bilateral involvement. The main manifestations were ground-glass opacity (87.9%) and multiple infiltration (83.5%) (Figure 2). No different imaging features were shown between imported and local patients (Table 3).

Treatment and prognosis of patients with COVID-19

The median time that patients stayed in the hospital was 14 days (IQR 11-18). All the patients took Chinese traditional medicinal treatment, and 89 (97.8%) patients were treated with antiviral therapy, including Lopinavir and Ritonavir (Kaletra), arbidol and atomized inhalation of interferon α. In total, 22 patients were treated with immunoglobulin, and 20 were treated with thymosin α-1. Overall, 13 patients received short-term corticosteroids treatment, with 40-80 mg/d methylprednisolone for 3-5 days. Only one patient needed extracorporeal membrane oxygenation (ECMO) but died. By Mar 24, 2020, 88 of 91 patients had been discharged, and 3 patients had died. There was no significant difference in the treatment, length of hospitalization or clinical outcome between the imported and local patients (Table 4). All the patients had been followed for more than 14 days after discharge, and no nucleic acid detection test for SARS-CoV-2 RNA was returned as positive. IgM and IgG antibodies against SARS-CoV-2 in plasma samples were tested in 83 patients in the follow-up at week 2 after discharge. IgM was positive in 33 patients (39.8%), and IgG was positive in 77 patients (92.8%). As some of the patients had left Hainan, only 43 patients had a second detection of antibodies in the follow-up at week 4 after discharge (median, 48 days from onset; IQR, 44-53 days). Among these patients, 88.4% (38/43) had a reduction in IgG levels. The IgG levels (median S/CO, 10.95; IQR, 3.74-20.95) at week 4 after discharge were significantly lower than the levels (median S/CO, 15.02; IQR, 4.24-36.23) at week 2 (P<0.001, Figure 3).

SARS-CoV-2 RNA in nasopharyngeal swabs and feces

We tested for SARS-CoV-2 RNA in nasopharyngeal swabs and feces of all the patients at an interval of 2 to 7 days dynamically. All 91 patients had detectable SARS-CoV-2 RNA in nasopharyngeal swabs, and 79 had detectable levels in feces. SARS-CoV-2 RNA could be detected in nasopharyngeal swabs and feces at medians of 11 days (IQR 6-16, range 1-39) and 13 days (IQR 10-19, range 1-40), respectively. The viral shedding durations in these two types of samples were 16 days (IQR 13-23, range 6-43 days) and 19 days (IQR 14-26, range 6-43) from onset, respectively. The durations of SARS-CoV-2 RNA testing being positive and viral shedding in feces were longer than that of nasopharyngeal swabs (P=0.02 and P=0.007, respectively). In samples (including nasopharyngeal swabs and feces) from three dead patients, the SARS-CoV-2 RNA remained positive on the day of death (37 days, 20 days and 17 days from symptom onset, respectively). There was no significant difference in the duration of SARS-CoV-2 RNA positivity or the duration of viral shedding in nasopharyngeal swabs and feces between the imported and local patients (Table 4).

According to the data released by the Hainan Health Commission [11], by Mar 24, 2020, 162 of 168 patients had been discharged and 6 patients had died, with a mortality rate of 3.6%. No new cases occurred after Feb 19, 2020 [14]. The 91 cases in this study accounted for 54.2% of all the confirmed cases in Hainan, and a similar trend was found in the epidemic course (see Figure 1). Of the 91 patients, three patients died. The mortality rate was similar to that of the whole Hainan Province.

Our study shows that during the 29-day epidemic period, most of the patients were diagnosed within the first three weeks after the first identified imported case. In the early period, imported cases were predominant in the epidemic. In the later period, local cases were more common, and 77.1% of the patients showed clustering, mainly in families. Cluster outbreaks were also found in Guangzhou patients in Lin’s study [17]. These findings suggest increasing transmissibility of the virus during the spread [18] and, hence, a great challenge in overall prevention and control. However, the local cases did not lead to continuous community transmission, as reflected by the short epidemic period (29 days). This may be attributed to the strict isolation and prevention measures implemented throughout the country and the effective implementation of prevention and control policies by Hainan (Figure 1). The measures included establishing fever clinics for screening suspicious patients, designating hospitals to focus on treating patients with COVID-19 [19], and raising the level of emergency response to COVID-19 prevention and control to the first level promptly at Day 4. At the same time, other measures also worked well in blocking the routes of transmission and reducing the chance of infection. Examples include encouraging the public to wear face masks, wash hands more frequently, and stay at home unless necessary and activating joint prevention and control mechanisms and cross-sector control for traffic control at the community level. Moreover, delaying the resumption of work and school and implementing work-from-home policies for employees and online teaching for students were adopted to reduce the probability of clusters [20]. The reported estimated incubation time of SARS‐CoV‐2 was based on limited data. Zhong reported that the median incubation period was 4 days in 291 cases in China [21]. Jiang Xu et al. found that there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), with a mean of 4.9 days for SARS-CoV-2, 4.7 days for SARS, and 5.8 days for MERS [22]. To avoid the risk of virus spreading, all potentially exposed subjects were required to be isolated for 14 days, which is the longest predicted incubation time. Our epidemiological investigation of 53 patients from Wuhan found that the median time of symptom onset was 5 days, with a range of 1 day to 34 days. The patient with the longest incubation period, who was a male in their 70s, flew from Wuhan to Hainan on January 2, 2020 and had no contact with confirmed or suspected COVID-19 patients. He occasionally went to the farmers' market near his residence to buy vegetables, but there were no confirmed COVID-19 patients associated with the market. He developed symptoms on February 5 and was diagnosed on February 7, 2020 [11]. This particular case indicates that the longest incubation time may be more than 34 days.

This study showed that the main symptoms of patients in Hainan Province were fever and cough, and 30% of patients had shortness of breath. Compared with early COVID-19 cases in Wuhan, diarrhea (14.3%) was relatively more common in Hainan patients [23]. The main complications included infections and ARDS. Six severe cases developed to MODS. In general, the proportions of severe patients and mortalities were lower than those of Wuhan and similar to the national data [24,25].

In the imported cases, the proportion of patients with fever, the peak temperature, the level of blood CRP, the proportion of severe cases, and the incidence of complications, especially infections, were higher than those in the local cases. Meanwhile, the lymphocyte and platelets counts were significantly lower in imported cases than in local cases. Data showed that the imported cases were older, and coexisting illness was more common than in local cases, which might demonstrate why the imported cases were more severe. Another possible explanation is that the time of infection SARA-CoV-2 in imported cases was earlier, with a more virulent virus subtype. However, this requires further study of the genomics and pathogenicity of SARA-CoV-2 at different stages of transmission. Tang's research indicates that SARS-CoV-2 had formed two subtypes, S and L, during the transmission process, and changes in viral genes will cause changes in pathogenicity and transmission [18]. A similar study had been conducted for the MERS virus, which had shown that the virus becomes weaker during transmission [26]. It remains to be further studied whether there was virus mutation in the process of virus transmission from imported cases to local cases, which may have led to the weakening of its pathogenicity. Furthermore, given the experience in Wuhan, the Hainan government was well-prepared for the epidemic, and comprehensive screening allowed early case identification and prompt treatment.

All 91 patients, including four asymptomatic patients, had CT changes in the lungs, which mainly manifested as ground-glass opacity in the lung periphery in the early stage. However, as the disease progressed, some patients had pulmonary consolidation and pleural effusion. Therefore, pulmonary CT examination is a sensitive indicator for the screening of COVID-19 and is recommended for all suspected patients [27].

Even so, SARS-CoV-2 RNA provides direct evidence for confirming COVID-19. Among all our patients, SARS-COV-2 RNA was detected in nasopharyngeal swabs, but RNA was not detected in 12 patients’ feces. Due to the positive detecting of SARS-CoV-2 RNA in feces, the problem of gastrointestinal transmission and even aerosol transmission has attracted broad attention. Since then, multiple research teams have isolated viruses in the feces, further illustrating the risk of gastrointestinal transmission.

However, for a new viral infectious disease, there is no exact data on how long virus will be shed through the respiratory and digestive tracts. Our study found that the median duration of fecal SARS-CoV-2 shedding was longer than that in nasopharyngeal swabs, with durations of 19 and 16 days, respectively. And the longest times of SARS-CoV-2 RNA persistent positive testing and viral shedding were 40 days and 43 days, respectively. The relatively long virus shedding duration could pose a great challenge for health systems as the patient pool flows slowly and takes up substantial health facility resources. While it is impossible to host all positive cases in hospitals throughout the virus shedding period, it is possible to shift less-acute cases to other temporary facilities as done in Wuhan. It is worth noting that the nasopharyngeal swabs and feces collected on the day of death of the three critically ill patients were still positive. This suggests that the persistence of the virus may have an impact on the disease prognosis, and it is urgent to screen and develop effective antiviral drugs.

Unfortunately, currently, there are no effective antiviral drugs. Drugs such as Remdesivir, kaletra, arbidol, chloroquine phosphate and some Chinese traditional medicines have shown certain effects but still lack rigorous and proven evidence [28-31]. Clinical trials of these drugs are currently ongoing. The treatment of all our patients was basically based on interferon alpha nebulization plus the antiviral regimen of arbidol or kaletra. However, without a controlled study, it is difficult to determine whether it is the natural fluctuation of the virus replication or the effect of the drug.

Since there were no available testing kits in the early stage of the COVID-19 epidemic, data on antibodies against SARS-CoV-2 were only collected in the follow-up after discharge. We observed a high positive rate of IgG and a reduction in the IgG level at a median of 48 days (IQR 44 to 53 days) from symptom onset, which was within 6 to 8 weeks from onset. As reported by Long, IgG levels start to decrease within 2-3 months after infection [32]. These findings may challenge attempts to control COVID-19 through universal immunization, as patients with reduced antibody levels may be re-infected. Of course, the subsequent changes in antibody levels require further observation.

There are some limitations in this study. Due to the barriers to data collection, the clinical data of all 168 patients in the entire Hainan Province have not been collected.

Our study revealed the epidemiological and clinical characteristics and outcomes of imported and local cases outside Hubei Province, suggesting that imported cases were more severe than local cases, but the prognoses could be similarly good. The short epidemic period in Hainan suggests that the epidemic could be quickly brought under control if proper timely measures were taken. This study also suggests that the longest incubation period for COVID-19 may be over 34 days and that the maximum duration of SARS-CoV-2 shedding is at least 43 days. The positive rate of SARS-CoV-2 IgG antibodies was high during convalescence; however, the level of IgG declined from week 6 to week 8 after onset.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Hainan General Hospital and The Second Affiliated Hospital of Hainan Medical University (HN-2020-31), and oral consent was obtained from all patients.

Consent for publication

Written informed consent for publication of the clinical details was obtained from the patients. A copy of the consent form is available for review by the Editor of this journal.

Availability of data and materials

With the permission of the corresponding authors, we can provide participant data without names and identifiers but not the study protocol, statistical analysis plan, or informed consent form. Data can be provided after the Article is published. Once the data can be made public, the research team will provide an email address for communication. The corresponding authors have the right to decide whether to share the data based on the research objectives and plan provided.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was funded by the National Science and Technology Major Project (Bing-Liang Lin, 2018ZX10302204, Bing-Liang Lin, 2017ZX10203201003), the Emergency special program for 2019-nCoV of Guangdong province science and technology project (GDSTP-ESP) (Zhi-Liang Gao, 2020B111105001) and the Tackling of key scientific and emergency special program of Sun Yat-sen University [SYSU-TKSESP, Bing-Liang Lin].

Authors' contributions

B Wu, ZY Lei, KL Wu, JR He, J Fu, F Chen, Y Chen, B Chen, XL Zhou, T Wu, YG D, SX Chen, FR Xiao, J He, F Lin and BL Lin collected the epidemiological and clinical data and processed the statistical data. ZY Lei, HJ Cao and BL Lin drafted the manuscript. BL Lin, F Lin and J He revised the final manuscript. BL Lin and F Lin were responsible for summarizing all data related to the virus and clinical data. B Wu and KL Wu were responsible for summarizing all epidemiological data. F Lin, B Wu and BL Lin provided administrative, technical, or material support. All authors read and approved the final manuscript.

Acknowledgements

We thank all patients involved in the study. We thank Mrs. Xulan Fu, Hao Lin for proofreading this manuscript. Jian-Rong He was supported by the China Scholarship Council-University of Oxford Joint Scholarship.

COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ARDS, acute respiratory distress syndrome; CT, computed tomography; CRP, C-reactive protein; PCT, procalcitonin; CDC, Centre for Disease Control and Prevention; MODS, multiple organ dysfunction syndrome; ECMO, extracorporeal membrane oxygenation.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020 Feb 3. doi: 10.1038/s41586-020-2012-7
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33. doi:10.1056/NEJMoa2001017.
COVID-19 Coronavirus – Update. https://virusncov.com/ (accessed August 21, 2020)
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5.
Li X, Zai J, Wang X, Li Y. Potential of large "first generation" human-to-human transmission of 2019-nCoV. J Med Virol. 2020 Apr;92(4):448-454. doi: 10.1002/jmv.25693.
Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020 Feb 13. pii: taaa021. doi: 10.1093/jtm/taaa021.
Zhao S, Musa SS, Lin Q, Ran J, Yang G, Wang W et al. Estimating the Unreported Numberof Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak. J Clin Med. 2020 Feb 1;9(2). pii: E388. doi: 10.3390/jcm9020388.
Xu K, Cai H, Shen Y, Ni Q, Chen Y, Hu S et al. Management of corona virus disease-19 (COVID-19): the Zhejiang experience. ZhejiangDa Xue Xue Bao Yi Xue Ban. 2020 Feb 21;49(1):0.
Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tearsand conjunctival secretions of patients with SARS-CoV-2 J Med Virol. 2020 Feb 26. doi: 10.1002/jmv.25725.
http://www.comrc.com.cn/news/html (accessed August 21, 2020)
http://wst.hainan.gov.cn/yqfk/(accessed August 21, 2020)
World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infections suspected: interim guidance. Published January 28, 2020. Accessed August 21, 2020.
Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514-23. doi:10.1016/S0140-6736(20)30154-9.
Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4. doi:10.1186/s40779-020-0233-6.
Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment JAMA. 2018 Feb 20;319(7):698-710. doi: 10.1001/jama.2017.21907.
Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST.
Lei Ziying, Cao Huijuan, Jie Yusheng, Huang Zhanlian, Guo Xiaoyan, Chen Junfeng, et al. A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China.[J] .Travel Med Infect Dis, 2020, Volume 35, May–June 2020, 101664. DOI: 1016/j.tmaid.2020.101664.
Tang X, Wu C, Li X, Song Y, Yao X, Wu X et al. On the origin and continuing evolution of SARS-CoV-2. National Science Review, nwaa036, https://doi.org/10.1093/nsr/nwaa036 (accessed August 21, 2020)
http://wst.hainan.gov.cn/swjw/rdzt/yqfk/202001/t20200131_2742298.html (accessed August 21, 2020)
http://www.gov.cn/zhengce/content/2020-01/27/content_5472352.html (accessed August 21, 2020)
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020. doi:10.1056/NEJMoa2002032.
Jiang X, Rayner S, Luo MH. Does SARS-CoV-2 has a long incubation period than SARS and MERS? J Med Virol.2020 Feb 13. doi: 10.1002/jmv.25708.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. doi:10.1016/S0140-6736(20)30211-7.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020. doi:10.1001/jama.2020.1585.
Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. 2020 Feb 19;368:m606. doi: 10.1136/bmj.m606.Kim KH, Tandi TE, Choi JW, Moon JM, Kim MS. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications. J Hosp Infect 2017;95:207-13. doi:10.1016/j.jhin.2016.10.008
Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology. 2020 Feb 12:200343. doi: 10.1148/radiol. 2020200343
Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatmentof COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Feb 19. doi: 10.5582/bst.2020.01047
Zhang Q, Wang Y, Qi C, Shen L, Li J. Clinical trial analysis of 2019-nCoV therapy registered in China. J Med Virol. 2020 Feb 28. doi: 10.1002/jmv.25733.
Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for 2019 Novel Coronavirus. Zhong Hua Jie He He Hu Xi Za Zhi. 2020 Feb 5;43(0): E002. doi: 10.3760/cma.j.issn.1001-0939. 2020.0002.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. doi:10.1038/s41422-020-0282-0.
Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J et al: Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med DOI: 10.1038/s41591-020-0965-6.

Table 1. Demographics and epidemiological characteristics of patients with COVID-19

All patients

(N=91)

Local cases (N=35)

Imported cases

(N=56)

P values

Characteristics

Age, years, Mean (SD)

Range

≤29

30-39

40-49

50-59

60-69

≥70

Sex

Female

Male

Chronic medical illness

Hypertension

Cardiovascular disease

Diabetes

Respiratory system disease

Thyroid disease

Chronic liver disease

Chronic kidney disease

Digestive system disease

Malignant tumor

Other

50 (14)

21-83

6 (6.6%)

20 (22.0%)

15 (16.5%)

25 (27.5%)

19 (20.9%)

6 (6.6%)

39 (42.9%)

52 (57.1%)

31 (34.1%)

12 (13.2%)

5 (5.5%)

7 (7.7%)

2 (2.2%)

5 (5.5%)

3 (3.3%)

2 (2.2%)

1 (1.1%)

6 (6.6%)

46 (12)

21-73

2 (5.7%)

10 (28.6%)

8 (22.9%)

9 (25.7%)

5 (14.3%)

1 (2.9%)

16 (47.2%)

19 (52.8%)

8 (22.9%)

2 (5.7%)

1 (2.9%)

0 (0.0%)

1 (2.9%)

0 (0.0%)

1 (2.9%)

52 (15)

27-83

4 (7.1%)

10 (17.9%)

7 (12.5%)

16 (28.6%)

14 (25.0%)

5 (8.9%)

23 (41.1%)

33 (58.9%)

23 (41.1%)

10 (17.9%)

4 (7.1%)

5 (8.9%)

6 (10.7%)

2 (3.6%)

4 (7.1%)

2 (3.6%)

1 (1.8%)

0 (0.0%)

5 (8.9%)

0.030

0.410

0.670

0.074

0.120

0.645

0.152

0.243

0.521

0.645

1.000

0.385

0.400

Epidemiological survey

Live or travel history in epidemic area*

Time of out of epidemic area to onset, days, n=53, Median (IQR), [range]

Close contacts with COVID-19 patient

Time of contacted COVID-19 patient to onset, days, n=26, Median (IQR) [range]

Cluster outbreak

53 (58.2%)

5 (2-10) [1-34]

42 (46.2%)

26/42; 8(4-13) [1-22]

53 (58.2%)

0 (0.00%)

NA

24 (68.6%)

17/24; 6 (4-15) [1-22]

27 (77.1%)

53 (94.6%)

5 (2-10) [1-34]

18 (32.1%)

9/18; 8 (5-16) [2-20]

26 (46.4%)

<0.001

NA

0.001

0.570

0.004

Data are n (%) unless specified otherwise. N is the total number of patients with available data. ARDS=acute respiratory distress syndrome. COVID-19=coronavirus disease-19. P values for comparing two groups were derived using Fisher’s exact test for categorized variables and the t-test for continuous variables.

*Epidemic area refers to Wuhan and other epidemic areas in Hubei Province.

NA, not available.

Table 2. Clinical characteristics of patients with COVID-19

All patients

(N=91)

Local cases

(N=35)

Imported cases (N=56)

P values

Illness station

First symptom to, Median (IQR), days

Hospital admission

ARDS

Admission to intensive care unit

Clinical classification

Mild

Severe

5.0 (3.0-9.0)

8.0 (5.5-9.5)

9 (9.9%)

76 (83.5%)

15 (16.5%)

6.0 (2.0-10.0)

N=2, Range 4-6

2 (5.7%)

32 (91.4%)

3 (8.6%)

5.0 (3.0-7.8)

N=7, 9.0 (6.0-10.0)

7 (12.5%)

44 (78.6%)

12 (21.4%)

0.670

0.184

0.291

0.149

Signs and symptoms

Fever

Peak temperature, °C, Median (IQR)

Days of fever, Median (IQR)

Dry cough

Expectoration

Fatigue

Shortness of breath

Myalgia

Diarrhea

Sore throat

Nausea and vomiting

More than one sign or symptom

Fever, cough, and shortness of breath

72 (79.1%)

38.0 (37.5-38.7)

8.0 (4.0-10.0)

72 (79.1%)

36 (39.6%)

35 (38.5%)

27 (29.7%)

11 (12.1%)

13 (14.3%)

10 (11.0%)

7 (7.7%)

87 (95.6%)

23 (25.3%)

21 (60.0%)

37.8 (36.9-38.6)

6.0 (3.0-10.5)

30 (85.7%)

16 (45.7%)

11 (31.4%)

9 (25.7%)

3 (8.6%)

2 (5.7%)

33 (94.3%)

7 (20.0%)

51 (91.1%)

38.0 (37.7-38.7)

8.0 (4.8-10.0)

42 (75.0%)

20 (35.7%)

24 (42.9%)

18 (32.1%)

8 (14.3%)

10 (17.9%)

8 (14.3%)

5 (8.9%)

54 (96.4%)

16 (28.6%)

0.001

0.028

0.506

0.221

0.343

0.276

0.639

0.521

0.218

0.306

0.703

0.637

0.360

Complication

Any

Infection

ARDS

Septic shock

Cardiac insufficiency

Metabolic acidosis

Acute renal injury

MODS

14(15.4%)

14 (15.4%)

9 (9.9%)

8 (8.8%)

5 (5.5%)

6 (6.6%)

2 (5.7%)

2 (2.9%)

1 (2.9%)

12 (21.4%)

7 (19.6%)

7 (12.5%)

6 (10.7%)

7 (12.5%)

4 (7.1%)

5 (8.9%)

0.043

0.474

0.706

0.146

0.645

0.400

Data are n (%) unless specified otherwise. N is the total number of patients with available data.

COVID-19=coronavirus disease-19. ARDS=acute respiratory distress syndrome. MODS=multiple organ dysfunction syndrome. P values for comparing two groups were derived using Fisher’s exact test for categorized variables and the t-test for continuous variables.

Table 3. Laboratory data and imaging findings of patients with COVID-19

All patients

(N=91)

Local cases

(N=35)

Imported cases (N=56)

P values

Blood routine

White cell count (×10⁹/L), Mean (SD)

>10.0

<4.0

Lymphocytes (×10⁹/L), Mean (SD)

< 1.1

Platelets (×10⁹/L), Mean (SD)

<150

Hemoglobin (g/L), Mean (SD)

5.45 (2.42)

5 (5.5%)

21 (23.1%)

1.26 (0.62)

39 (42.9%)

205.8 (69.9)

23 (25.3%)

133.0 (18.1)

5.57 (1.70)

1 (2.9%)

5 (14.3%)

1.45 (0.59)

8 (22.9%)

239.7 (68.3)

3 (8.3%)

131.7 (17.7)

5.38 (2.79)

4 (7.1%)

16 (28.6%)

1.14 (0.61)

31 (55.4%)

184.6 (62.6)

20 (35.7%)

133.8 (18.5)

0.502

0.645

0.116

0.022

0.002

0.001

0.005

0.412

Blood biochemistry

Alanine aminotransferase (U/L, normal range 3-35), Median (IQR)

Increased (n, %)

Aspartate aminotransferase (U/L, normal range 3-40), Median (IQR)

Increased (n, %)

Total bilirubin (μmol/L, normal range 4.0-17.1), Median (IQR)

Increased (n, %)

Albumin (g/L, normal range 35.0-55.0), Median (IQR)

Decreased (n, %)

PT (sec), Median (IQR)

Serum creatinine (μmol/L), Median (IQR)

Creatine kinase (U/L), Median (IQR)

C-reaction protein (mg/L), Median (IQR) Procalcitonin (ng/mL), Median (IQR)

21.3 (14.7-34.8)

20 (22.0%)

22.0 (17.0-30.1)

12 (13.2%)

9.0 (6.5-13.4)

13 (14.3%)

42.3 (36.2-47.1)

18 (19.8%)

11.3 (10.8-11.8)

65.8 (48.0-76.9)

63.0 (46.0-93.6)

12.3 (2.2-45.1)

0.04 (0.02-0.06)

22.0 (15.0-31.0)

6 (17.1%)

24.0 (20.0-32.0)

4 (11.4%)

9.8 (5.9-13.9)

3 (8.6%)

46.7 (41.4-49.6)

4 (11.4%)

11.3 (10.3-12.4)

68.0 (50.9-77.0)

70.0 (46.0-127.0)

5.3 (1.2-30.5)

0.04 (0.02-0.09)

20.7 (13.8-35.4)

14 (25.0%)

20.0 (15.3-28.0)

8 (14.3%)

8.4 (6.5-11.8)

10 (17.9%)

39.3 (34.7-44.4)

14 (25.0%)

11.4 (10.8-12.5)

59.0 (47.0-76.8)

62.0 (45.0-84.0)

17.0 (3.0-51.3)

0.03 (0.01-0.06)

0.427

0.379

0.170

0.761

0.410

0.218

0.001

0.114

0.407

0.835

0.013

0.022

0.778

Chest CT finding

Unilateral pneumonia

Bilateral pneumonia

Lung periphery

Ground-glass opacity

Multiple Infiltration

Bilateral lung periphery ground-glass opacity

Nodule

Lung consolidation

Pleural effusion

16 (17.6%)

75 (82.4%)

79 (86.8%)

80 (87.9%)

76 (83.5%)

70 (76.9%)

11 (12.1%)

8 (8.8%)

2 (2.2%)

8 (22.9%)

27 (77.1%)

29 (82.9%)

30 (85.7%)

26 (74.3%)

25 (71.4%)

2 (5.7%)

3 (8.6%)

0 (0.0%)

8 (14.3%)

48 (85.7%)

50 (89.3%)

45 (80.4%)

9 (16.1%)

5 (8.9%)

2 (3.6%)

0.296

0.526

0.743

0.061

0.325

0.193

1.000

0.521

Data are n (%) and mean (SD). N is the total number of patients with available data. COVID-19=coronavirus disease-2019. P values for comparing two groups were derived using Fisher’s exact test for categorized variables and the t-test for continuous variables.

Table 4. Treatment, virus changes and outcomes of patients with COVID-19

All patients

(N=91)

Local cases (N=35)

Imported cases (N=56)

P value

Treatment

Chinese traditional medicine

Antiviral therapy

Oxygen therapy

Intravenous immunoglobulin therapy

Thymosin alpha1

Glucocorticoids

Intravenous antibiotic

Mechanical ventilation

Non-invasive (i.e., face mask)

Invasive

ECMO

91 (100.0%)

89 (97.8%)

46 (50.5%)

22 (24.2%)

20 (22.0%)

13 (14.3%)

12 (13.2%)

10 (11.0%)

1 (1.1%)

9 (9.9%)

1 (1.1%)

35 (100.0%)

33 (94.3%)

14 (40.0%)

5 (14.3%)

9 (25.7%)

3 (8.6%)

2 (5.7%)

1 (2.9%)

56 (100.0%)

32 (57.1%)

17 (30.4%)

11 (19.6%)

10 (17.9%)

8 (14.3%)

0 (0.0%)

8 (14.3%)

0 (0.0%)

1.000

0.112

0.306

0.081

0.496

0.218

0.120

0.385

0.145

0.385

0.145

Hospital stay, days, Median (IQR)

14 (11-18)

14 (11-17)

15 (11-14)

0.403

Duration of SARS-CoV-2 RNA positivity from onset

Nasopharyngeal swabs, days

Median (IQR), [range]

Feces, days

Median (IQR), [range]

11 (6-16)

[1-39]

79/91, 13 (10-19)

[1-40]

8 (5-16)

[1-37]

29/35, 13 (6-18)

[1-37]

12 (8-16)

[4-39]

50/56, 13 (10-20)

[4-40]

0.084

0.216

Duration of SARS-CoV-2 shedding from onset

Nasopharyngeal swabs, days

Median (IQR), [range]

Feces (days)

Median (IQR), [range]

16 (13-23)

[6-43]

79/91, 19 (14-26)

[6-43]

15 (10-22)

[8-37]

29/35, 18 (11-24)

[6-37]

17 (14-23)

[6-43]

50/56, 19 (15-27)

[8-43]

0.148

0.242

Clinical outcome

Discharged

Died

88 (96.7%)

3 (3.3%)

34 (97.1%)

1 (1.1%)

54 (96.4%)

2 (3.6%)

1.000

Data are n (%) and mean (SD). N is the total number of patients with available data. COVID-19=coronavirus disease-2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. ECMO=extracorporeal membrane oxygenation. NA, not available. P values for comparing two groups were derived using Fisher’s exact test for categorized variables and the t-test for continuous variables.

Epidemiological and clinical features of imported and local patients with coronavirus disease 2019 (COVID-19) in Hainan, China

Status:

Journal Publication

Version 2

Abstract

Figures

Introduction

Methods

Results

Discussion

Conclusion

Declarations

Abbreviations

References

Tables

Status:

Journal Publication

Version 2