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Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020

We report a superspreading event of severe acute respiratory syndrome coronavirus 2 infection initiated at a bar in Vietnam with evidence of symptomatic and asymptomatic transmission, based on ministry of health reports, patient interviews, and whole-genome sequence analysis. Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission.

We studied the development and persistence of neutralizing antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing antibodies against ancestral strain, Delta variant, BA.1, and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research.

We tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated that there was no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. Future studies should look at pre-existing B cell and T cell memory in pre-pandemic samples in Vietnam, which might further shed light on the pathogenesis of the infection.

BackgroundOne hundred days after SARS-CoV-2 was first reported in Vietnam on January 23rd, 270 cases have been 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.MethodsClinical 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 captured by Vietnam’s National Steering Committee for COVID-19 response. 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.FindingsAfter the first confirmed case on January 23rd, the Vietnamese Government initiated mass communications measures, case-contact tracing, mandatory 14-day quarantine, school and university closures, and progressive flight restrictions. A national lockdown was implemented between April 1st and 22nd. 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. 21 developed severe disease, with no deaths. 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 15th.InterpretationVietnam 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.FundingThe Vietnam Ministry of Health and Wellcome Trust, UK.Research in contextEvidence before this studyVietnam was one of the first countries outside of China to detect imported and human-to-human transmitted SARS-CoV-2 within its borders. Yet, as of May 1st, a total of only 270 cases have been confirmed, no deaths have occurred, and no community transmission has been detected since April 15th despite intensive screening, tracing and testing. We did a PubMed database search to identify studies investigating COVID-19 response in Vietnam using the terms “Vietnam”, “COVID-19”, and “SARS-CoV-2”. All relevant articles were evaluated. Studies describe cases of COVID-19 and their management, aspects of the government response from newspapers and online government sources, but there are no previous reports using national data to describe and investigate the national epidemic and the impact of control measures cases over time.Added value of this studyWe used data from the National Steering Committee for COVID-19 response to give a comprehensive account of the first 100 days of the SARS-CoV-2 epidemic in Vietnam, including case numbers and their symptomatology, the estimated reproductive number by week, and their relation to the multiple control measures instituted by the Vietnam Government over time. We show two distinctive features of Vietnam’s response. First, the Government took rapid actions to restrict international flights, closed schools and universities, and instituted meticulous case-contact tracing and quarantining from late January, well before these measures were advised by WHO. Second, they placed mass communication, education, and the identification, serial testing, and 14-day quarantine of all direct contacts of cases, regardless of symptom development, at the heart of the response. The value of strict contact-tracing and quarantine is supported by the high proportion of asymptomatic cases (43%) and imported cases (60%), and evidence for substantial pre-symptomatic transmission.Implications of all the available evidenceVietnam has had remarkable success in controlling the emergence of SARS-CoV-2. Our report provides a complete picture of the control of SARS-CoV-2 in Vietnam, with lessons for other Governments seeking to extend national SARS-CoV-2 control or prevent future epidemics. Our findings shows the importance of acting early, before the virus becomes established in the community, and before the case numbers overwhelm systems of case-contact tracing and mass quarantine. They also demonstrate the value of effective mass communication in rapidly educating the public in infection prevention measures and providing real-time information on the state of the epidemic.

Background Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited. Methods We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing. Findings Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms. Interpretation Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.