The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

Background: Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.

Results: Between 10 March and 4 April 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. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts.

Conclusions: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.

Keywords: COVID-19; SARS-CoV-2; Vietnam; coronaviruses; pandemic.

Figure 1.

Timelines of containment strategies applied in Vietnam and in Ho Chi Minh City (HCMC) since the beginning of 2020 as the epidemic/pandemic progresses alongside the implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) testing and the duration of the clinical study. *Initially China, followed by Korea, other European counties (Italy, France, United Kingdom, etc.) and the United States.

Figure 2.

Settings and the clinical study. A, Map showing the location of the Hospital for Tropical Diseases (HTD) main campus and its designated coronavirus disease 2019 centers in Cu Chi, where the clinical study was conducted, and Can Gio. B, Flowchart illustrating the results of reverse-transcription polymerase chain reaction screening of quarantined people between 10 March and 5 April 2020, and the enrollment of patients in the clinical study. *Extrapolated from data extracted from the HTD database system. During this period, HTD tested a total of 11 052 cases, accounting for 80% of isolated people in Ho Chi Minh City (HCMC). **The remaining cases were either treated at the main campus of HTD in HCMC or at the other designated isolation center (Can Gio Hospital). ^#One was transferred to the main campus of HTD 10 hours after admission and 2 were transferred from the main campus of HTD after 5 and 6 days of hospitalization and were not enrolled because of enrollment competition. Maps were obtained from https://mapchart.net/. Abbreviations: HCMC, Ho Chi Minh City; HTD, Hospital for Tropical Diseases; PCR, polymerase chain reaction; RT-PCR, reverse-transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Comparison of cycle threshold values of severe acute respiratory syndrome coronavirus 2 real-time reverse-transcription polymerase chain reaction (RT-PCR) assays obtained from nasopharyngeal/throat swabs (NTSs) and saliva. A, Data include results of RT-PCR analysis of all available NTS and saliva samples collected from 30 participants at enrollment. B, Data only include results of RT-PCR analysis of paired NTS and saliva samples of 6 asymptomatic and 12 symptomatic patients who had both sample types collected at enrollment. Abbreviations: Ct, cycle threshold; NTS, nasopharyngeal/throat swab.

Figure 4.

Trends in cycle threshold (Ct) values and viral detection probability in nasopharyngeal/throat swabs over the course of hospitalization. A, Changes of Ct values relatively reflect the level of viral load. B, Dynamics of viral detection probability from enrollment onward. Each dot represents 1 observed value (A) or the mean value (ie, frequency) per day (B); lines indicate mean and shades indicate 95% confidence interval. Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.

Figure 5.

Illustration of cases with an epidemiological link with community transmission cluster 2. Red circles indicate symptomatic patients, whereas blue circles indicate asymptomatic individuals. Patients shown on the large open circle are those who first came to a local bar on 14 March 2020. Arrows indicate patients who tested positive for severe acute respiratory syndrome coronavirus 2 after having contact with individuals who attended the event on 14 March 2020. *Reflecting the period from the first contacts among individuals shown on the large open circle (14 March 2020) to the time when local health authorities completed the contact tracing activities and reverse-transcription polymerase chain reaction screening of the contacts (6 April 2020). Patient numbers correspond to the numbers presented in Supplementary Figure 2. Abbreviation: P, patient.