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).

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.

Background: Gaps remain in the detection of nucleic acid test (NAT) yield and occult hepatitis B virus (HBV) infection (OBI) by current HBV surface antigen (HBsAg) assays. The lack of detection may be due to HBsAg levels below current assay detection limits, mutations affecting HBsAg assays or HBsAg levels, or the masking of HBsAg by antibody to HBsAg (anti-HBs). In this study, we evaluate the incremental detection of NAT yield and OBI from five diverse geographic areas by an improved sensitivity HBsAg assay and characterize the samples relative to the viral load, anti-HBs status, and PreS1–S2–S mutations. Included is a comparison population with HBV DNA levels comparable to OBI, but with readily detectable HBsAg (High Surface–Low DNA, HSLD). Methods: A total of 347 samples collected from the USA, South Africa, Spain, Cameroon, Vietnam, and Cote D’Ivoire representing NAT yield (HBsAg(−), antibody to HBV core antigen (anti-HBc)(−), HBV DNA(+), N = 131), OBI (HBsAg(−), anti-HBc(+), HBV DNA(+), N = 188), and HSLD (HBsAg(+), anti-HBc(+), HBV DNA(+), N = 28) were tested with ARCHITECT HBsAg NEXT (HBsAgNx) (sensitivity 0.005 IU/mL). The sequencing of the PreS1–S2–S genes from a subset of 177 samples was performed to determine the genotype and assess amino acid variability, particularly in anti-HBs(+) samples. Results: HBsAgNx detected 44/131 (33.6%) NAT yield and 42/188 (22.3%) OBI samples. Mean HBV DNA levels for NAT yield and OBI samples were lower in HBsAgNx(−) (50.3 and 25.9 IU/mL) than in HBsAgNx(+) samples (384.1 and 139.5 IU/mL). Anti-HBs ≥ 10 mIU/mL was present in 28.6% HBsAgNx(+) and 45.2% HBsAgNx(−) OBI, and in 3.6% HSLD samples. The genotypes were A1, A2, B, C, D, E, F, and H. There was no significant difference between HBsAgNx(−) and HBsAgNx(+) in the proportion of samples harboring substitutions or in the mean number of substitutions per sample in PreS1, PreS2, or S for the NAT yield or OBI (p range: 0.1231 to >0.9999). A total of 21/27 (77.8%) of HBsAgNx(+) OBI carried S escape mutations, insertions, or stop codons. HSLD had more PreS1 and fewer S substitutions compared to both HBsAgNx(−) and HBsAgNx(+) OBI. Mutations/deletions associated with impaired HBsAg secretion were observed in the OBI group. Conclusions: HBsAgNx provides the improved detection of NAT yield and OBI samples. Samples that remain undetected by HBsAgNx have exceptionally low HBsAg levels below the assay detection limit, likely due to low viremia or the suppression of HBsAg expression by host and viral factors.

Table 1 Characteristics of the included studies. Author Country Cases (n) Male (%) Age (years) § Study design