key: cord-0912135-lbv3rpe7
authors: Chen, Chi-Ling; Lai, Chao-Chih; Luh, Dih-Ling; Chuang, Shao-Yuan; Yang, Kuen-Cheh; Yeh, Yen-Po; Ming-Fang Yen, Amy; Chang, King-Jen; Chang, Ray-E; Li-Sheng Chen, Sam
title: Review of Epidemic, Containment Strategies, Clinical Management, and Economic Evaluation of COVID-19 Pandemic
date: 2021-05-27
journal: J Formos Med Assoc
DOI: 10.1016/j.jfma.2021.05.022
sha: d12e64cc8ef2d08db888133f2a57b374fee0c330
doc_id: 912135
cord_uid: lbv3rpe7

The spread of the emerging pathogen, named as SARS-CoV-2, has led to a unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light om the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on an inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (NPIs and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

Human history on pandemic caused by the emerging infectious disease has been documented during the period from sixteen to eighteen century mainly afflicted by the Plague 1 . In early 1918, there was a pandemic around the world named as "Spain Flu" afflicting the countries worldwide in parallel with the contemporaneous period of War I. This 1918 influenza pandemic not only led to the imminent squeal of more than 500 million infected cases and at least 50 million deaths but also produced the influence on societal and economic loss due to containment measurements without vaccine and antivirals. [1] [2] [3] [4] Most importantly, although the 1918 pandemic has been tentatively controlled by the implementation of nonpharmaceutical interventions (NPIs) at that time it has also shown a series of far-reaching impacts on both health and societal perspectives.

The former has been noted by sequences of the following influenza pandemics including H2N3 in 1957 and 1968 and Avian Flu during 1997 and 2004 and H5N2 in 2009 5, 6 . As far as non-health impacts, the 1918 influenza pandemic had been long postulated to be highly associated with 1929 Great Depression worldwide with the implementation of very strict containment measurements such as isolation and lockdown polices. 7, 8 J o u r n a l P r e -p r o o f There is a continental transition of influenza pandemic, shifting from the preponderance of the 1918 pandemic in Western countries (the USA and Europe) to the emergence of its viral variants in Asian countries of those subsequent influenza pandemics after 1918 pandemic. 2 Of note, avian influenza emerged in several Asian regions, including Thailand, Vietnam, China, and so on. 9 It is also very interesting to note that, in addition to influenza pandemic, two large-scale outbreaks regarding the Corona series of virus such as SARS in 2003 and MERS in 2015 also emerged in the Province of Guangdong in south-eastern China and also Korea. In 2003, the emerging SARS has been spread from China, Hong Kong, to Taiwan, resulting in several large-scale community-acquired outbreaks. [10] [11] [12] The continental spread of COVID-19 was the opposite of that of 1918 pandemic. From historical viewpoint, there were many similarities between 1918. The emergence of SARS in 2003 heralded the potential of coronavirus as a pathogen responsible for large outbreak. 10, 11, 13 Similar to SARS-CoV-2, the outbreak of SARS in 2003 occurred through a series of clustered transmissions, typically occurred in crowded settings such as hospitals, hotels, and vehicles of public transportation. 10, 11, 14 Due to the characteristics of being infective after the presence of fever (Figure 2 (a) ), the containment strategies focusing on the measurement of body temperature were implemented widely. A typical application in Taiwan was the adaption of fever screening facilities into the working flow of health care services. 15 This preventive measure together with the routine implementation of universal precaution including wearing the facial mask and self-hygiene effectively mitigate the risk of large-scale clustered outbreak of SARS in Taiwan in 2003 15, 16 . Even though, the lack of specific tools for early identification of infected subjects and effective antiviral therapies for treating SARS patients resulted in a high case-fatality rate of SARS outbreak in 2003. With the experience of SARS outbreak, infection control measures including the reporting system, syndromic monitoring, procedures and facilities for isolating patients under the suspicion, and education programs for health care personnel have been incorporate as part of quality assurance program of health care institutes in Taiwan. 16, 17 The implementation and regulation of border control, isolation, and quarantine from early period of outbreak until the entire COVID-19 J o u r n a l P r e -p r o o f pandemic period in Taiwan has rooted in the antecedent experiences on lockdown, isolation, and quarantine polices of SARS outbreaks in 2003.

A decade after the SARS outbreak, the Middle East respiratory syndrome (MERS) outbreak occurred in South Korea in May, 2015. 18 Similar to SARS, a novel coronavirus, MERS-CoV, was identified as the culprit pathogen for a series of clustered events occurred mainly in nosocomial settings in South Korea in 2015. 12, 18 The MERS-CoV was first identified in Saudi Arabia in 2012. 19 Although the animal reservoir of camel was proposed as the main source of infection in early phase, 20 the clustered events raised serious concerns over human to human transmission. [21] [22] [23] This concern was consolidated by the community-acquired outbreak of MERS in South Korea in 2015 following the introduction of the MERS-CoV into the hospital caring for a 68 years old patient with travel history to Middle East. 18 The comparison between SARS, MERS, COVID-19 is summarized in Table 1 . The incubation period of SARS-CoV-1 is 4.7 days (95% CI: 4.3-5.1). The incubation period for MERS (5.8 days (95% CI: 5.0-6.5) and SARS-CoV-2 (5.3 days (95% CI: 5.0-6.5) are longer. The infectious period of SARS-CoV-1 is 8.4 days (95% CI: 3-14) but shorter for SARS-CoV-2 (7.0 days (95% CI: 4.5-10.4)) and longer for MERS (12.6 days (95% CI:

12.1-13.1)). The reproductive numbers for three highly pathogenic human coronaviruses are close with ranged from 2.6-3.0. Compared with the very low J o u r n a l P r e -p r o o f case-fatality rate (2.1%), the case-fatality rate for SARS and MERS are high (27%-32%). A higher 32.1% fatality rate with a significantly higher risk among the elder subjects and those with comorbidities was revealed in a detailed analysis. 12 The discovery of anti-therapy and vaccine for COVID-19 might be the partial reason for lower fatality.

The community-acquired outbreaks of SARS and MERS vividly showed the potential of coronavirus in inducing global pandemic with the serious outcomes of remarkable case-fatality rate. A better understanding for distinct characteristics of latent period and incubation period between SARS and MERS and SARS-CoV-1 may give a clue to the transmission and the spread of SARS-CoV-2. infected with SARS-CoV-2 become infectious to infect the susceptible subjects before the occurrence of symptoms related to COVID-19. This character accounts for why the epidemic caused by SARS-CoV-2 is more intractable to be prevented than that of SARS as those infectives before symptoms have been proven as pre-symptomatic and asymptomatic cases later during COVID-19 pandemic.

A phenotyping evolution and spatiotemporal clustering phenomenon of the emerging infectious disease, COVID-19, from southern China to countries of the 38 o North Latitude via international travel was noted. [27] [28] [29] [30] [31] By international mobility after the outbreak in China, several countries had initial outbreak by the rapidly virus spread in the early of 2020. 26, 32 In South Korea, the first COVID-19 case, an imported case from China, was confirmed in mid-January. The first outbreak of COVID-19 in J o u r n a l P r e -p r o o f South Korea started from the end of January to 19 February. Due to the church cluster infection, the second outbreak started from 20 February. 27, 33 By 26 February, the government of South Korea implemented the universal testing of COVID-19, and the daily reported cases grew up rapidly. 34 The epidemic curve started to decline since 4

March. In Iran, two deaths were reported on 19 February and confirmed as the first two cases of COVID-19 in the same day in Iran. 35, 36 Another outbreak broke out on March 24, with more than 1500 daily reported cases occurred up to the end of March.

In Rome, Italy, the first two cases of COVID-19 cases who came from Wuhan were confirmed on 31 January. 37, 38 In Lombardy, Italy, the fourth confirmed case was reported on 21 February. After several sporadic cases been reported, extensive tests were performed on everyone who had possibly been in contact with the infected subjects. 39 A superspreader in Lombardy started to accumulate a big cluster. After then, the cases numbers in Italy increased dramatically. For other countries in Europe, the case reported from beginning were related to China or Italy. The time series of main outbreak started in other countries surrounding Italy, such as France and Germany.

The COVID-19 outbreaks were further spread to the United Kingdom, Scandinavian countries, and other European countries. 40 The first confirmed case in USA was also related to China. 40 March 2020, 45 underestimating the high SARS-CoV-2 attack and slow reaction in most of Public Health Systems led to the rapid spread of COVID-19 resulting in global pandemic after an initial outbreak was observed. 46 Similar to the outbreak occurring in South Korea, Italy, and Iran during the early period, the intrusion of this novel pathogen started from imported cases, followed by the clustered transmission in scenarios of close contact such as household, mass gathering event, and health care facilities including hospitals and long-term care institutes. 14, 31, 33, [47] [48] [49] With this augmentation, the COVID-19 outbreak has established its ground and transformed into community-acquired outbreaks lasting for periods before its containment by the implementation of a series of NPIs in the country and region with outbreak. NPIs have been suggested to slow the spread of infection before widespread of effective vaccinations. 50 Due to the characteristics of COVID-19 transmission in the pre-symptomatic and asymptomatic state and the high transmissibility as indicated above, several waves of community-acquired outbreaks occurred. The fatal consequences of this long lasting pandemic due to both the high mortality among the elder population and the collapse of health care system in the face of overwhelming cases resulted in an emergent and stringent situation for containing COVID-19 spreading at regional and global scale. [51] [52] [53] Given the dilemma of using NPIs as a main strategy for the J o u r n a l P r e -p r o o f containment of outbreaks and its tremendous impact of societal and economical activities, the decision on the timing and the extent of lifting social distancing is always scientifically and politically challenging, 54 even in the early months of 2021 when effective vaccines are available.

Conventionally, the basic reproductive number (R 0 ) is used to quantify the outbreak and the risk of community-acquired outbreak as indicated in Figure 3 . The outbreak will continue when R 0 >1, whereas the outbreak is controlled while R 0 <1. 55 The effective reproductive number (R e ) is calculated over time as an indicator together with R 0 to explain the effect of containment and mitigation strategies. 56 However, relying on reproductive number to manage COVID-19 pandemic is limited. 57 This convention of using effective reproductive number (R e ) for the identification of community-acquired outbreak based on which the implementation or lifting of NPIs has been confronted by this long lasting and capricious COVID-19 pandemic. No other indicator has been discussed more controversially than the reproduction number. 58 pandemic a series of data-driven models taking into account the duration taken from R t > 1 to R t < 1 and case load given each duration was developed. On the basis of this data-driven model, the COVID-19 outbreaks in global countries and regions were categorized into fiver patterns, labelled as "controlled epidemic", "mutant propagated epidemic", "propagated epidemic", "persistent epidemic" and "long persistent The first domestic case was diagnosed on January 28, 2020 in Taiwan, also caused by a family cluster infection because his wife traveled back from Wuhan. 62 The higher household attack rate in the early period of COVID-19 pandemic than SARS-CoV and MERS-Cov has been demonstrated in a systematic review study. 63 Prompt adoption of containment measurements can reduce the probability from The NPIs from the conventional approaches of quarantine and isolation to the lockdown at different scale have been implement for containing COVID-19 outbreak since first pandemic period. The NPI of lockdown has been used to contain the outbreak in countries such as Italy. 38, 65, As part of the border control measures, the effectiveness of NPIs have also been demonstrated in countries such as Taiwan. 42, 66 With the vaccination distribution by the end of year 2020, the NPIs still play a role in containing COVID-19 outbreak due to both the uncertainty of vaccine efficacy in preventing asymptomatic cases and SARS-CoV-2 transmission and the attenuated protection against the emerging variant strains since the third pandemic period. [67] [68] [69] [70] [71] Although a series of NPIs have been adopted in countries and regions globally since the early period of first COVID-19 pandemic, its effectiveness in preventing outbreak can hardly been addressed systematically and empirically. 72.73 This is also true for the implementation of NPIs in conjunction with vaccination distribution.

We thus evaluated the efficacy of NPIs for containing the outbreak of COVID-19 before and after vaccination by using a computer simulation design in conjunction with the susceptible-exposed-infected-recovered (SEIR) type model. cases in the first and third pandemic period, the shortage of medical care capacity in terms of facilities, equipment, and personnel have been reported by most of the medical care systems worldwide. [80] [81] [82] [83] [84] The negative association between the overburdened medical care system due to mounting COVID-19 cases and the risk of disease progression and death have been well established. 85 The emergence of viral variants with enhanced transmissibility further exacerbates this threat. 86 To predict fatal COVID-19 with a surrogate indicator, the medical capacity can be allocated with precision to provide an optimal treatment and to reduce the risk of COVID-19 death.

To address this issue and to provide a real-time monitoring between the balance of medical needs and capacity, Hsu et al. developed an index for predicting the occurrence of fatal COVID-19 by using the progression rate from pneumonia to acute respiratory distress syndrome (ARDS). 79 A significant association between this progression index and the reported case fatality rate reported in each county was found (R 2 =95%). In addition, a remarkable variation ranging from 3% to 63% for each county, which was attributed to the corresponding case-fatality rate for each 

While the preparedness of medical care capacity is of paramount importance for caring COVID-19 patient, effective treatments and therapies not only can alleviate the risk of disease progression but also accelerate discharge for efficient utilization of medical care resources. 88 94, 95 The timely provision of these antiviral therapies tailored by disease severities can decrease the risk of COVID-19 death and accelerate the rate of recovery and discharge. 90, 96 Following the convention of evidence-based clinical practice, several randomized controlled trials have been conducted to prove the clinical efficacy of these compounds. [97] [98] [99] [100] [101] [102] [103] [104] [105] [106] [107] Based on the double-blind, randomized, placebo-controlled trial ACTT-1 study, remdesivir therapy showed the efficacy in decreasing the risk of COVID-19 death by 27% with a marginally statistically significance. 97, 98 In order to clarify the inconsistent or underpowered results of remdesivir treatment efficacy, a novel study design and analysis was proposed by Jen et al. 108 The study demonstrated that remdesivir treatment can significantly decrease the risk of COVID-19 death by 21%. The number needed to treat of remdesivir treatment required to avoid one death Allocation of medical capacity has been also affected by SARS-CoV-2 variants of concern (VOCs) that have emerged since late 2020. 116 Several studies showed that B.1.1.7 is more likely to transmit to children and the P.1 variant can cause more severe clinical presentations in young adult. 117, 118 . A study in Canada demonstrated that the medical needs of hospitalization and ICU care for COVID-19

increased by 21% and 28%, respectively, in March 2021. 119 The study further revealed that in Ontario, Canada, the percentage of ICU admission among patients under 60 years have been increasing since December 2020, by when 67% of COVID-19 cases was infected by B.1.1.7 strain. 119 Modelling the medical needs for hospitalization, ICU, and home-based setting may resort to a compartment queue model in conjunction with the congestion indices for isolation wards and ICU. The compartment queue model to describe the process from susceptible, self-quarantine and self-isolation at home/hospital, ICU admission to recovery/death, estimating the traffic intensity ratios (TIRs) for the congestion of hospitalization and ICU by taking Lombardy (Italy), France, Spain, Belgium, New York State (USA), South Korea, and Japan for example. These two TIRs can monitor the medical capacity in hospital in response to the COVID-19 pandemic. The higher TIRs the more demand is required to meet increasing cases. TIRs derived from compartment Queue model can be applied to assessing the preparedness of medical capacity during COVID-19 resurgence. The application and the results of these context are provided in the 8 th accompanying article of this special issue. 120

Non-pharmaceutical interventions were the only effective means to contain the spread of COVID-19 before the roll-out of vaccines in the epoch of COVID-19 pandemic. A simple hand-hygiene was demonstrated as cost-effective with an ICER of USD $8 only. 121 Screening tests and social distancing are also believed to be cost-effective. 122 The vaccines with the efficacy in preventing SARS-CoV-2 infection, symptomatic COVID-19, severe COVID-19 state, and COVID-19 death have become available in the beginning of 2021. [123] [124] [125] According to the reports of Phase 3 randomized controlled trials of the three major vaccines, BNT162b2 

The COVID-19 pandemic has caused huge impact on human life in terms of both health and economical outcomes. Following this long-lasting and unprecedented threat to human life, a shorten life expectancy has been foreseen given the high incidence and mortality and prevailed spreading COVID-19. 128 The authors have nothing to disclose.

The authors have no conflicts of interest relevant to this article. [133] 95% CI: 4.3-5.1 5.8 [133] 95% CI: 5.0-6.5 5.3 [24] 95% CI: 4.0-6.9

Infectious period(days) 8.4 [134] 95% CI: 3-14 12.6 [135] 95% CI: 12.1-13.1 7.0 [24] 95% CI: 4.5-10.4

Reproductive number 3.0 [136] 2.6 [137] 2.8 [44] Case-fatality rate 27.0% [15] 32.1% [12] 2.1% [138] Anti 

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Modeling and forecasting trend of COVID-19 epidemic in Iran until May 13, 2020

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The effect of interventions on COVID-19

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