Viral load differences between asymptomatic and symptomatic patients with SARS-CoV-2 infection
In a cohort study that included 303 patients with SARS-CoV-2 infection isolated in a community treatment center in the Republic of Korea, 110 (36.3%) were asymptomatic at the time of isolation and 21 of these (19.1%) developed symptoms during isolation, states the JAMA Network website. The study was published online in JAMA Intern Med.
The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients. That means many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients; therefore, isolation of infected persons should be performed regardless of symptoms. There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending healthcare personnel carefully identified patients’ symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription–polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days eight, nine, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients.
Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients. The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients.
In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.
The findings demonstrate that 80.9% (95% CI, 77.2%-84.6%) of patients with SARS-CoV-2 who were asymptomatic at the time of detection of a positive RT-PCR remained asymptomatic during a median (IQR) of 24 (20-26) days from diagnosis, and the Ct values in asymptomatic patients were similar to those in symptomatic patients. A previous study in a long-term care facility showed that 56.5% of patients with SARS-CoV-2 infection were asymptomatic at the time of diagnosis, and 23.1% remained asymptomatic during seven. As mathematically estimated in Diamond Princess cruise ship patients, the proportion of asymptomatic cases was 17.9%. In a population-based study in Iceland, 43% of 1221 participants who tested positive were asymptomatic initially, although symptoms developed later. In these previous reports, presymptomatic patients were also considered asymptomatic cases because the clinical course of asymptomatic cases was not observed. In our study, asymptomatic patients who were required to be isolated in a CTC according to government policy were fully observed by health care personnel. An important implication of our findings is that there may be substantial underreporting of infected patients using the current symptom-based surveillance and screening.
Little is known about the infectiveness of asymptomatic patients. Our findings, given a recent report of SARS-CoV-2 transmission from an asymptomatic person to 4 family members, nevertheless offer biological plausibility to such reports of transmission by asymptomatic people. A previous study analyzing a small number of patients also reported that viral load of asymptomatic SARS-CoV-2 patients was as high as that of symptomatic patients. Although the high viral load we observed in asymptomatic patients raises a distinct possibility of a risk for transmission, our study was not designed to determine this. In this study, Ct values of env genes from LRT specimens in asymptomatic patients tended to decrease more gradually than those of symptomatic patients. It appears that the env target signal was aberrant owing to fragmented or degraded genomes. The genetic material of dead viral particles remaining within epithelial cells can be detected as epithelial cells are desquamated. In a recent study, viral shedding from sputum has been shown to extend beyond symptom duration. It is important to note that detection of viral RNA does not equate infectious virus being present and transmissible. For a better understanding of the viral shedding and potential transmissibility of asymptomatic infection, large rigorous epidemiologic and experimental studies are needed.
