key: cord-0918953-oyizfh2z authors: Pham, Quang Thai; Rabaa, Maia A; Duong, Huy Luong; Dang, Quang Tan; Tran, Dai Quang; Quach, Ha-Linh; Hoang, Ngoc-Anh Thi; Phung, Cong Dinh; Ngu, Duy Nghia; Tran, Anh Tu; La, Ngoc Quang; Tran, My Phuc; Vinh, Chau; Nguyen, Cong Khanh; Dang, Duc Anh; Tran, Nhu Duong; Thwaites, Guy; van Doorn, H Rogier; Choisy, Marc title: The first 100 days of SARS-CoV-2 control in Vietnam date: 2020-08-01 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa1130 sha: ee26fa7758e935421df83ad1be186619554748c7 doc_id: 918953 cord_uid: oyizfh2z BACKGROUND: One hundred days after SARS-CoV-2 was first reported in Vietnam on January 23(rd), 270 cases were confirmed, with no deaths. We describe the control measures used by the Government and their relationship with imported and domestically-acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control. METHODS: Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of Government control measures, including numbers of tests and quarantined individuals, were analysed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of pre-symptomatic transmission events and time-varying reproduction numbers. RESULTS: A national lockdown was implemented between April 1(st) and 22(nd). Around 200 000 people were quarantined and 266 122 RT-PCR tests conducted. Population mobility decreased progressively before lockdown. 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3·24 days, and 27·5% (95% confidence interval, 15·7%-40·0%) of transmissions occurred pre-symptomatically. Limited transmission amounted to a maximum reproduction number of 1·15 (95% confidence interval, 0·37-2·36). No community transmission has been detected since April 15(th). CONCLUSIONS: Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city, Hubei Province, China, in late 2019 [1] . On January 30 th , the WHO declared the outbreak a 'Public Health Emergency of International Concern', and on March 11 th a global pandemic. By May 1 st 2020, the virus had infected more than 3 million people and killed over 200 000. SARS-CoV-2 is antigenically different from known human and zoonotic coronaviruses and there is no known pre-existing population immunity [2] . It is highly transmissible through respiratory secretions expelled from an infected person, with a basic reproduction number (R 0 ) estimated between 2 and 3 in the absence of control measures [3] [4] [5] [6] . Many infections are asymptomatic [7] , while others lead to symptoms of coronavirus disease (COVID-19) of varying severity [5] . Analyses of serial intervals suggest that contagiousness can occur both before and after the onset of symptoms as well as in those who never develop symptoms [8] . The subsequent exponential rise in infections has threatened to overwhelm even the world's best developed health systems and cause major loss of life. Methods to control the virus and reduce the impact of COVID-19 have thus become a global priority. The preparedness, timing, and nature of the response to SARS-CoV-2 have varied substantially between countries. Many affected countries have resorted to extreme social distancing measures through so-called 'lockdowns', where populations isolate themselves within their homes, reducing all but essential contact with others. As first observed in Hubei Province in China, and subsequently in other countries, these measures slow transmission and reduce disease incidence [9] [10] [11] , but at significant social and economic cost. However, 'lockdowns' represent a combination of potentially independent interventions (for example, closing schools and universities, suspending public transport, banning public gatherings, closing non-essential businesses), the effects of which in isolation are uncertain. Determining their relative contributions to SARS-CoV-2 control is critical to understanding how they might be safely and incrementally lifted, or partially reinstated. Such A c c e p t e d M a n u s c r i p t 6 information may be acquired from studying the measures employed by countries that have so far controlled the virus. Vietnam is a low-middle income country that shares borders with China, The Lao People's Democratic Republic, and Cambodia. It is the 15 th most populous country on earth, with 97.3 million people, and it was one of the first countries affected by SARS-CoV-2, recording its first case on January 23 rd 2020. Yet, by May 1 st , 270 cases were confirmed, with no deaths [12] . Here we present a descriptive study that aims to characterize and quantify measures used for SARS-CoV-2 and characteristics of the cases in Vietnam during the first 100 days of the epidemic. Our aim was to identify the measures most closely associated with successful SARS-CoV-2 control. Clinical, epidemiological and policy data were provided by Vietnam's National Steering Committee for COVID-19 response. Data from 270 SARS-CoV-2-confirmed cases to May 1 st 2020 included their age, gender, nationality, dates of symptom onset (if any), entry to the country and quarantine (if any), hospital admission and discharge, and the results of RT-PCR tests. Imported cases were distinguished from those acquired domestically, with information on quarantine at or after entry to the country. Imported cases were denoted G0; and among domestically-acquired infections, those acquired directly from G0 cases were denoted as G1, others were denoted G2+. Intervention data consisted of daily time-series of the numbers in quarantine and RT-PCR tests performed. Daily reports from the Ministry of Health and Vietnam's National Steering Committee for COVID-19 response listed key milestones in national SARS-CoV-2 control measures. Apple mobility data [13] and Google community mobility data [14] provided proxies of population movements, with additional information provided in the Supplementary Appendix. Serial intervals were calculated from dates of symptoms onset of infector-infectee pairs identified by contact tracing and fitted to a normal distribution by maximum likelihood [8] . The estimated A c c e p t e d M a n u s c r i p t 7 distribution parameters (mean and standard deviation, together with their confidence intervals and variance-covariance matrix) were used to estimate the proportion of pre-symptomatic transmissions and three time-varying reproduction numbers [15] : between G0 and G1 (step 1), between G1 and G2+ (step 2), and between G0, G1, and G2+ combined (step 1 and 2 combined)(further details in the Supplementary Appendix). We used a logistic regression to investigate the link between the proportion of asymptomatic infections and age, gender, nationality (Vietnamese versus non-Vietnamese), and imported versus domestically-acquired infection. We used a gamma regression to investigate the link between the duration of hospitalisation and the same variables listed above, plus symptomatic versus asymptomatic. To correct for potential confounding effects between the explanatory variables, we used Type-II likelihood ratio tests [16] . All analyses were done with R 4.0.0 [17] On January 10 th , before the first case was confirmed in Vietnam, the Vietnam Government reinforced temperature and health status screening at border gates for passengers arriving from Wuhan, tracing and quarantining of suspected cases and their contacts, monitoring of suspected cases of respiratory infections in hospitals and the community, and initiated mass communication to the public on preventive measures (hand washing, contact avoidance and mask wearing). The epidemic timeline for Vietnam, including the numbers quarantined and hospitalised, tests performed, cases confirmed, population movements, and the timing and nature of major Government-led control measures are summarised in Figure 1 . The control measures are summarised in Table 1 and Table S1 . To date, two waves of transmission have occurred: the first A c c e p t e d M a n u s c r i p t 8 began on January 23 rd and resulted in 16 cases (9 imported, 7 acquired in-country), and the second on March 6 th , leading to 254 cases (154 imported, 100 acquired in-country). The first confirmed cases of SARS-CoV-2 infection presented in Hanoi and Ho Chi Minh City during the lunar New Year holiday (23-29 th January). Cases were travellers from Wuhan city or their contacts, and were identified by the public health laboratory network using improvised molecular diagnostics, including agnostic sequencing, prior to implementation of the WHO-approved assays [22] . Amongst the cases were the first confirmed human-to-human transmissions outside of China [23] . Entry of airline passengers into Vietnam from Wuhan city and elsewhere in China was monitored and progressively limited ( Table 1) After further measures to prevent entry of infected international travellers (Table 1) Forty-three percent (89/208) of discharged cases never developed symptoms, and this was not significantly associated with age, gender, nationality, or origin of infection (imported or domestically-acquired). Among all the symptomatic cases, 25·3% (38/150) developed symptoms in a Government quarantine facility. Among the imported cases who developed symptoms, 73·9% (68/92) did so after entry to the country ( Figure 3A , see Table S4 for the numbers of symptomatic in imported and non-imported cases). The median age of symptomatic and asymptomatic cases was 30 (IQR 24-49) and 31 (IQR 23-45), respectively (no significant effect of age on the probability to develop symptoms, Figure 3C ). Among the 150 with symptoms, 21 (14·0%) developed severe disease, of whom five required mechanical ventilation and two received extra-corporeal membrane oxygenation. No fatalities were recorded. The duration of hospitalisation was significantly shorter (p<0·0001) for asymptomatic (17 days, IQR 13-22) than for symptomatic cases (19 days, IQR [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] . While gender, nationality, and origin of infection did not have any significant effect, the duration of hospitalisation of symptomatic cases increased with age (with a discharge rate decreasing by 1·24% for every year older, p = 0·0060) (Figure 3B) . A c c e p t e d M a n u s c r i p t 11 From 33 infector-infectee pairs, the mean serial interval was estimated to be 3·24 days (95% confidence interval (CI), 1·38-5·10 days) with a standard deviation of the distribution of 5·46 days (95% CI, 4·14-6·78 days). An estimated 27·5% (95% CI, 15·7%-40·0%) of the distribution was below zero, suggesting these transmissions occurred prior to the onset of symptoms in the infector ( Figure 3D ). From the (non-quarantined) imported cases (G0) and onward infected cases (G1 and G2+), we calculated the effective reproductive number R by date (Figure 1F-H) . Limited transmission amounted to a maximum R of 1·15 (95% CI, 0·37-2·36). R rarely exceeded 1 and a decrease of R is seen as more mitigating measures were implemented from the end of March before the nationwide lockdown. When analysing R from G0 to G1 (step 1) and from G1 to G2+ (step 2) separately, we found that R was drastically decreased for step 1 simultaneously with suspension of all international travel (March 18 th ), while for step 2 transmission continues with R slightly above 1 despite intense contact tracing and quarantine. Only during the nationwide lockdown R was reduced to less than 1 ( Figure 1F and G) . On January 23 rd 2020, Vietnam was one of the first countries to report SARS-CoV-2 infection and the first to report human-to-human transmission outside of China [23] . Yet 100 days later, it confirmed just 270 cases despite extensive testing, with no community transmission since April 15 th . In the three weeks prior to May 1 st , there were only two imported cases and no reported cases elsewhere in the country. The nature, timing, and success of the control measures introduced may have relevance to other countries seeking to control SARS-CoV-2 transmission. Vietnam has experience in responding to emerging infectious diseases. In the last 20 years, it has confronted outbreaks of SARS [26] , avian and pandemic influenza [27, 28] , hand-foot-and-mouth disease [29] , measles [30] , and dengue [31] . Its outbreak responses are coordinated by the Ministry days of an epidemic that is likely to continue for many months. It is therefore impossible to conclude definitively which of these control measures have resulted in the current control of SARS-CoV-2 in Vietnam and whether they will continue to work in the future. There are, however, two distinctive features of Vietnam's response. First, the Government acted quickly, educating and engaging the public, placing restrictions on international flights, closing schools and universities, and instituting exhaustive case-contact tracing from late January, well before these measures were advised by WHO. Second, they placed the identification, serial testing, and minimum 14-day isolation of all direct contacts of cases, regardless of symptom development, at the heart of the response. Our findings suggest the latter measure was likely to be especially effective given nearly half of those infected did not develop symptoms. Table S1 ). The colours shown in the phase column indicate the intensity of control measures taken over different periods (white, initial; light yellow, early; light orange, intermediate; orange, pre-epidemic; brown, epidemic/lockdown; dark orange, post-lockdown), and correspond to those used in Figure 1 and Table S1 . Event January 3 Strengthening of border control measures announced by the Government Table S3 . Panel D: distribution of serial intervals for 33 infector-infectee pairs together with a normal distribution fitted to it. The shaded area shows the 95% confidence interval. The vertical black line shows the estimate of the mean serial interval, together with its 95% confidence interval (dashed vertical lines). The proportion of the distribution to the left of the red line is a proxy for the proportion of infections that occur before the onset of symptoms. 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