Background Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. Methods We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. Conclusions Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.

248 2 1 Main text: 2788 2 2 Running title: Asymptomatic SARS-CoV-2 infection 2 3 ABSTRACT 2 5 Background 2 6Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its 2 7 contribution to infection transmission. 2 8 Methods 2 9We conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, 3 0 Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, 3 1 collecting clinical data, travel and contact history, and saliva at enrolment and daily 3 2 nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and 3 3 transmission potential of asymptomatic and symptomatic individuals.3 4 Results 3 5Between March 10 th and April 4 th , 2020, 14,000 quarantined people were tested for SARS-3 6CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms 3 7 and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. 3 8 Compared with symptomatic individuals, asymptomatic people were less likely to have 3 9 detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) 4 0 P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the 4 1 asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability 4 2 of RT-PCR positivity showed asymptomatic participants had faster viral clearance than 4 3 symptomatic participants (P<0.001 for difference over first 19 days). This difference was most 4 4 pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared 4 5 to transmit the infection to up to four contacts. 4 6 Conclusions 4 7 Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or 4 8 NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit 4 9 the virus to others. 5 0 Hospitals, located approximately 60 km to the West and East, respectively, of HCMC (Figure 9 7 2A).

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 11 th –25 th 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=0.002). 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. Funding Wellcome and NIH/NIAID

Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia.IMPORTANCE EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.