Investigating COVID-19 transmission in a tertiary hospital in Hanoi, Vietnam using social network analysis.

OBJECTIVES: In March 2020, a COVID-19 outbreak in a major referral hospital in Hanoi, Vietnam led to 7664 patients and staff being sent into lockdown for 2 weeks, and more than 52,200 persons across 49 provinces being quarantined. We assessed SARS-CoV-2 transmission patterns during this to-date largest hospital outbreak in Vietnam using social network analysis (SNA). METHODS: We constructed a directed relational network and calculated network metrics for 'degree', 'betweenness', 'closeness' and 'eigenvector' centrality to understand individual-level transmission patterns. We analysed network components and modularity to identify sub-network structures with disproportionately big effects. RESULTS: We detected 68 connections between 46 confirmed cases, of whom 27 (58.7%) were ancillary support staff, 7 (15.2%) caregivers, 6 (13%) patients and 2 (4.4%) nurses. Among the 10 most important cases selected by each SNA network metric, transmission dynamics clustered in 17 cases, of whom 12 (70.6%) cases were ancillary support staff. Ancillary support staff also constituted 71.1% of cases in the dominant sub-network and 68.8% of cases in the three largest sub-communities. CONCLUSIONS: We identified non-clinical ancillary support staff, who are responsible for room service and food distribution in hospital wards in Vietnam, as a group with disproportionally big impacts on transmission dynamics during this outbreak. Our findings call for a holistic approach to nosocomial outbreak prevention and response that includes both clinical and non-clinical hospital staff. Our work also shows the potential of SNA as a complementary outbreak investigation method to better understand infection patterns in hospitals and similar settings.

Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey.

BACKGROUND: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. METHODS AND FINDINGS: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. CONCLUSIONS: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.

The efficacy, safety and immunogenicity Nanocovax: results of a randomized, double-blind, placebo-controlled Phase 3 trial. (preprint)

Background Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. In a Phase 1 and 2 studies, (NCT04683484) the vaccine was found to be safe and induce a robust immune response in healthy adult participants. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and protective efficacy of the Nanocovax vaccine against Covid-19 in approximately 13,007 volunteers aged 18 years and over. The immunogenicity was assessed based on Anti-S IgG antibody response, surrogate virus neutralization, wild-type SARS-CoV-2 neutralization and the types of helper T-cell response by intracellular staining (ICS) for interferon gamma (IFNg) and interleukin-4 (IL-4). The vaccine efficacy (VE) was calculated basing on serologically confirmed cases of Covid-19. Findings Up to day 180, incidences of solicited and unsolicited adverse events (AE) were similar between vaccine and placebo groups. 100 serious adverse events (SAE) were observed in both vaccine and placebo groups (out of total 13007 participants). 96 out of these 100 SAEs were determined to be unrelated to the investigational products. 4 SAEs were possibly related, as determined by the Data and Safety Monitoring Board (DSMB) and investigators. Reactogenicity was absent or mild in the majority of participants and of short duration. These findings highlight the excellent safety profile of Nanocovax. Regarding immunogenicity, Nanocovax induced robust IgG and neutralizing antibody responses. Importantly, Anti S-IgG levels and neutralizing antibody titers on day 42 were higher than those of natural infected cases. Nanocovax was found to induce Th2 polarization rather than Th1. Post-hoc analysis showed that the VE against symptomatic disease was 51.5% (95% confidence interval [CI] was [34.4%-64.1%]. VE against severe illness and death were 93.3% [62.2- 98.1]. Notably, the dominant strain during the period of this study was Delta variant. Interpretation Nanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%.

Re-positive testing, clinical evolution and clearance of infection: results from COVID-19 cases in isolation in Viet Nam.

OBJECTIVE: Asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and test re-positivity after a negative test have raised concerns about the ability to effectively control the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the prevalence of COVID-19 asymptomatic and pre-symptomatic infections during the second wave of COVID-19 in Viet Nam, and to better understand the duration of SARS-CoV-2 infection and the dynamics between the evolution of clinical symptoms and SARS-CoV-2 test positivity among confirmed COVID-19 cases. METHODS: We conducted a cohort analysis on the first 50 confirmed cases during the second COVID-19 wave in Viet Nam using clinical, laboratory and epidemiological data collected from 9 March to 30 April 2020. Kaplan-Meier estimates were used to assess time to clearance of SARS-CoV-2 infection, and log-rank tests were used to explore factors related to time to SARS-CoV-2 infection clearance. RESULTS: Most cases (58%) had no typical signs or symptoms of COVID-19 at the time of diagnosis. Ten cases (20%) were re-positive for SARS-CoV-2 during infection. Eight cases (16%) experienced COVID-19 symptoms after testing negative for SARS-CoV-2. The median duration from symptom onset until clearance of infection was 14 days (range: 6-31); it was longer in re-positive and older patients and those with pre-existing conditions. CONCLUSION: Asymptomatic and pre-symptomatic infections were common during the second wave of COVID-19 in Viet Nam. Re-positivity was frequent during hospitalization and led to a long duration of SARS-CoV-2 infection.

Association of public health interventions and COVID-19 incidence in Vietnam, January to December 2020.

BACKGROUND: Vietnam implemented various public health interventions such as contact tracing and testing, mandatory quarantine, and lockdowns in response to coronavirus disease 2019 (COVID-19). However, the effects of these measures on the epidemic remain unclear. METHODS: This article describes the public health interventions in relation to COVID-19 incidence. Maximum likelihood estimations were used to assess containment delays (time between symptom onset and start of isolation) and multivariable regression was employed to identify associated factors between interventions and COVID-19 incidence. The effective reproductive numbers (Rt) were calculated based on transmission pairs. RESULTS: Interventions were introduced periodically in response to the epidemic. Overall, 817 (55.4%) among 1474 COVID-19 cases were imported. Based on a serial interval of 8.72 ± 5.65 days, it was estimated that Rt decreased to below 1 (lowest at 0.02, 95% CI 0-0.12) during periods of strict border control and contact tracing, and increased ahead of new clusters. The main method to detect cases shifted over time from passive notification to active case-finding at immigration or in lockdown areas, with containment delays showing significant differences between modes of case detection. CONCLUSIONS: A combination of early, strict, and consistently implemented interventions is crucial to control COVID-19. Low-middle income countries with limited capacity can contain COVID-19 successfully using non-pharmaceutical interventions.

Successful containment of a flight-imported COVID-19 outbreak through extensive contact tracing, systematic testing and mandatory quarantine: Lessons from Vietnam.

BACKGROUND: The importation of SARS-CoV-2 through air travel poses substantial risks to generate new COVID-19 outbreaks. Timely contact tracing is particularly crucial to limit onwards transmission in settings without established community transmission. METHODS: We conducted an in-depth analysis of the response to a big flight-associated COVID-19 outbreak in Vietnam in March 2020 that involved contact tracing, systematic testing and strict quarantine up to third generation contacts. RESULTS: 183 primary contacts from the flight as well as 1000 secondary and 311 third generation contacts were traced, tested, and quarantined across 15 provinces across Vietnam. The protracted confirmation of the index case at 3 days and 19 h after arrival resulted in isolation/quarantine delays of 6.8 days (IQR 6.3-6.8) and 5.8 days (IQR 5.8-7.0) for primary and secondary cases, respectively, which generated 84.0 and 26.4 person-days of community exposure from primary and secondary cases, respectively. Nevertheless, only 5 secondary cases occurred. CONCLUSIONS: A large flight-related COVID-19 cluster was successfully contained through timely, systematic and comprehensive public health responses despite delayed index case identification. Multiagency collaboration and pre-established mechanisms are crucial for low and middle income countries like Vietnam to limit community transmission after COVID-19 importation through air travel.

Timeliness of contact tracing among flight passengers during the COVID-19 epidemic in Vietnam.

BACKGROUND: International air travel plays an important role in the global spread of SARS-CoV-2, and tracing of close contacts is an integral part of the public health response to COVID-19. We aimed to assess the timeliness of contact tracing among airline passengers arriving in Vietnam on flights containing COVID-19 cases and investigated factors associated with timeliness of contact tracing. METHODS: We included data from 2228 passengers on 22 incoming flights between 2 and 19 March 2020. Contact tracing duration was assessed separately for the time between the date of index case confirmation and date of contact tracing initiation (interval I), and the date of contact tracing initiation and completion (interval II). We used log-rank tests and multivariable Poisson regression models to identify factors associated with timeliness. RESULTS: The median duration of interval I and interval II was one (IQR: 1-2) and 3 days (IQR: 2-5), respectively. The contact tracing duration was shorter for passengers from flights where the index case was identified through mandatory testing directly upon arrival (median = 4; IQR: 3-5) compared to flights with index case detection through self-presentation at health facilities after arrival (median = 7; IQR: 5-8) (p-value = 0.018). Cumulative hazards for successful tracing were higher for Vietnamese nationals compared to non-Vietnamese nationals (p < 0.001). CONCLUSIONS: Contact tracing among flight passengers in the early stage of the COVID-19 epidemic in Vietnam was timely though delays occurred on high workload days. Mandatory SARS-CoV-2 testing at arrival may reduce contact tracing duration and should be considered as an integrated screening tool for flight passengers from high-risk areas when entering low-transmission settings with limited contact tracing capacity. We recommend a standardized risk-based contact tracing approach for flight passengers during the ongoing COVID-19 epidemic.

Transmission of SARS-CoV 2 during long-haul flight

To assess the role of in-flight transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we investigated a cluster of cases among passengers on a 10-hour commercial flight. Affected persons were passengers, crew, and their close contacts. We traced 217 passengers and crew to their final destinations and interviewed, tested, and quarantined them. Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). Seating proximity was strongly associated with increased infection risk (risk ratio 7.3, 95% CI 1.2-46.2). We found no strong evidence supporting alternative transmission scenarios. In-flight transmission that probably originated from 1 symptomatic passenger caused a large cluster of cases during a long flight. Guidelines for preventing SARS-CoV-2 infection among air passengers should consider individual passengers' risk for infection, the number of passengers traveling, and flight duration.

Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020.

We analyzed 2 clusters of 12 patients in Vietnam with severe acute respiratory syndrome coronavirus 2 infection during January-February 2020. Analysis indicated virus transmission from a traveler from China. One asymptomatic patient demonstrated virus shedding, indicating potential virus transmission in the absence of clinical signs and symptoms.