key: cord-354780-yzyixucr
authors: Lin, Chih-Yen; Wang, Wen-Hung; Urbina, Aspiro Nayim; Tseng, Sung-Pin; Lu, Po-Liang; Chen, Yen-Hsu; Yu, Ming-Lung; Wang, Seng-Fan
title: Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan
date: 2020-06-13
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.06.031
sha: 
doc_id: 354780
cord_uid: yzyixucr

Abstract Objective COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate current status of COVID-19 in Taiwan and analyze the source of infection. Methods National data regarding SARS-CoV-2 infection were obtained from Taiwan CDC at the end of April, 2020. These data were subjected for analysis of the current status and correlation between indigenous and imported COVID-19 cases. Phylogenetic tree was performed to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates. Results The initial case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most of cases were identified as imported (79.9%; 343/429) with majority transmitted from United States of America (22.1%) and United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%). Conclusion This study suggests that importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.

other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%).

This study suggests that importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.

Keywords: COVDI-19, Taiwan, imported, indigenous Short Communication:

Emerging diseases pose a threat to global health and has the potential to become fatal. In December 2019, an atypical pneumonia prompted by a novel coronavirus, was first reported Wuhan, China (Huang et al., 2020) . This novel coronavirus was initially named 2019-novel coronavirus (2019-nCoV), however, currently the name has been established as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); with the disease being named as coronavirus disease 2019 (COVID-19) (Coronaviridae Study Group of the International Committee on Taxonomy of, 2020) Since the first reported case, there has been a rapid increase in the number of cases, with outbreaks being reported in countries all over the world. The SARS-CoV-2 has gradually disseminated to Europe, America and Asia via travelers and has caused a COVID-19 pandemic since March (WHO., 2020b). The World Health Organization (WHO) declared the outbreak as a Public Health Emergency of International Concern on January 30, 2020 and an official J o u r n a l P r e -p r o o f 4 pandemic on March 11, 2020. As of April 30, 2020, more than 3.2 million cases of COVID-19 have been reported in 185 countries and territories, resulting in more than 229,000 deaths (WHO., 2020b).

Coronaviruses are non-segmented enveloped viruses with a single-stranded, positive-sense RNA genome. Coronaviruses are known to infect a variety of animals with some strains being capable of infecting human. In recent decades, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) has caused regional outbreaks, leading to high mortality in human infections (Peeri et al., 2020) . In 2003, there was an outbreak of SARS-CoV in Taiwan with 664 SARS probable cases and 346 laboratory confirmed cases (Taiwan

Taiwan is an island in the Pacific Ocean, located beside mainland China. International travel has an important role in the transmission of emerging or re-emerging infectious diseases in Taiwan . In recent decades, the interactions between Taiwan and China have become frequent and close. Through this close interaction, SARS-CoV-2 infection was initially detected in Taiwan on January 21, 2020 (Taiwan CDC.) (Fig.1A&1B ). This first case was a 50-year-old woman who was detected by a fever screen station in Taoyuan International Airport, as she arrived from Wuhan, China.

Since then, several sporadic COVID-19 cases have been detected in Taiwan between January to early March, 2020 (Fig.1A&1B ). Data indicates that the COVID-19 imported cases have dramatically increased since the middle of March (Fig.1A) . Before the mid of March, the incidence of COVID-19 importation was 0.58 average per day. After that, the incidence of COVID-19 importation increased to 10.57 average per day (Fig.1B) . We J o u r n a l P r e -p r o o f further investigated the source of these COVID-19 importation. Our results indicated that the imported COVID-19 cases were mainly from United States of America (22.1%), United Kingdom (17.6%) and France (6.5%) (Fig.1C ). In addition to imported cases, there were a few indigenous COVID-19 cases reported. According to Taiwan CDC, by the end of April, there were 429 COVID-19 laboratory confirmed cases with the fatality rate of 1.39%. Among these cases, 343 (79.9%) and 55 (12.8%) were identified as imported and indigenous COVID-19, respectively (Fig.1D ). The rest of cases (7.2%) remain questionable, as their source of infection were not clearly defined. Accordingly, we suggest that the constant importation of SARS-CoV-2 infection is the major risk factor leading the COVID-19 epidemic in Taiwan.

Further, the source of infection from the indigenous cases were traced. Results indicated that most of indigenous cases (81.8%; 45/55) had contact history or exposure to SARS-CoV-2 infected patients, SARS-CoV-2 contaminated devices or environment through a direct or indirect way (Fig.1D ). There were 10 (18%) indigenous COVID-19 cases that remained unclear has to their possible source of infection (Fig.1D) . We further addressed the phylogeny of the SARS-CoV-2 isolated in Taiwan. Results demonstrated that three Taiwanese isolates, collected in the early phase of the COVID-19 epidemic, were similar with other SARS-CoV-2 isolates from other countries with bootstrap value of 98% (Fig.2) . It was also noted that SARS-CoV-2 was sub-clustered with Bat SARS-like strains isolated from China (Bat-SL-CoVZXC21 and Bat-SL-CoVZC45) (bootstrap value 99%) (Fig.2) , indicating that SARS-CoV-2 might have possibly evolved from Bat SARS-like viruses. However, the source and origin of SARS-CoV-2 still remains controversial, and further studies are demanded.

To reduce the effects of COVID-19 importation to Taiwan, Taiwan CDC has implemented relevant prevention strategies. The international airport reinforced fever screening of arriving passengers, questioning about their travel history, and conducting health assessments. Travelers coming from COVID-19 affected countries were required to fill out a "Novel Coronavirus Health Declaration and Home Quarantine Notice". Furthermore, foreign nationals were prohibited to enter Taiwan since March 19, 2020 in response to COVID-19 pandemics.

The COVID-19 spectrum of illness severity has been divided into four types: mild, moderate, severe, and critical (2020, Gao et al., 2020 , WHO., 2020a . The WHO reported that fever, fatigue and dry coughing are considered the main clinical manifestations of COVID-19 patients. Other symptoms may include runny nose, myalgia, pharyngalgia, stuffy nose, and diarrhea, however, these are relatively less common (WHO., 2020b). In severe cases, the COVID-19 may become fatal due to respiratory failure, shock and organ failure. The clinical features of COVID-19 are shown in Table 1 .

With this novel coronavirus causing a pandemic, more and more evidences indicate that majority of the COVID-19 cases may not develop to have severe manifestations with some cases even remaining asymptomatic; nevertheless, these individual still have the ability to transmit the virus to others. Asymptomatic infections are identified as individuals testing positive for the detection of SARS-CoV-2 nucleic acid using RT-PCR (Gao et al., 2020) (Table 1) , however, these individuals do not display the typical clinical symptoms and there are no apparent abnormalities in their images, including lung X-ray film and computed tomography (CT). Taiwan CDC indicates that around 60-70% COVID-19 patients belonged to asymptomatic or mild cases (Taiwan CDC.) . Similar indicating that most SARS-CoV-2 infected patients were asymptomatic.

The reasons for majority COVID-19 infections displaying "none-to-mild symptom" remain unclear. It has been proved that SARS-CoV-2 invades cells by using angiotensin-converting enzyme 2 (ACE2), as its receptor (Zhou et al., 2020) . Expression of lower level of ACE2 or weaker binding capacity between SARS-CoV-2 and ACE2

should be an essential factor that leads to the absence of any clinical manifestations for asymptomatic infections. In addition, host major histocompatibility complex (MHC) is also proposed to play a certain role to mildly initiate and regulate the SARS-Cov-2 induced immunopathogenesis (Nguyen et al., 2020) . It is suggested that more clinical samples should be collected and a comparative examination of ACE2 as well as MHC typing should be carried out.

Here, we report the current status of COVID-19 epidemic in Taiwan. We found that importation of SARS-CoV-2 infection was the major risk factor correlating with the outbreak causing a threat to Taiwan.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 

The phylogenetic tree was constructed on the basis of nucleotide sequence of full-length genome (~29kb). The filled red circles indicates Taiwanese SARS-CoV-2 isolates. Analysis was performed by using MEGA 6 software and neighbor-joining method. Bootstrap support values > 70 are shown (1,000 replicates).

J o u r n a l P r e -p r o o f (3) Complicated with other organ failure Positive J o u r n a l P r e -p r o o f

Coronaviridae Study Group of the International Committee on Taxonomy of V. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

A Systematic Review of Asymptomatic Infections with COVID-19

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?

Imported dengue fever and climatic variation are important determinants facilitating dengue epidemics in Southern Taiwan

Clinical management of severe acute respiratory infection (SARI) when COVID-19

A pneumonia outbreak associated with a new coronavirus of probable bat origin

RR (respiratory rate)

SpO2 (blood oxygen saturation levels)

These data were referenced with previous publications

The authors wish to thank the staff from Center for Tropical

Disease Control for their assistance in data collection.

CYL and WHW prepared and revised the manuscript. ANU and CYL helped to analyze the data. YHC ,SPT and PLL revised and edited the manuscript. MLY and SWF conceived the study and revised the draft.