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).

SARS-CoV-2 and co-infections detection in nasopharyngeal throat swabs of COVID-19 patients by metagenomics

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

Metagenomics could detect SARS-CoV-2 in all eight nasopharyngeal/throat swabs with high/low viral loads, and rhinovirus in a co-infected patient. The sequenced viruses belonged to lineage B1. Because metagenomics could detect novel pathogen and co-infection, and generate sequence data for epidemiological investigation, it is an attractive approach for infectious-disease diagnosis.