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Coronavirus (COVID-19)

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea

Educational Objective
To understand the viral load differences amongst asymptomatic and symptomatic patients with COVID-19

1 Credit CME

JAMA Internal Medicine

Published Online: August 6, 2020

Original Investigation

Article Information and Disclosures

Seungjae Lee, MD¹;

Tark Kim, MD²;

Eunjung Lee, MD¹;

Cheolgu Lee, MD³;

Hojung Kim, MD⁴;

Heejeong Rhee, MD⁵;

Se Yoon Park, MD¹;

Hyo-Ju Son, MD¹;

Shinae Yu, MD⁶;

Jung Wan Park, MD⁶;

Eun Ju Choo, MD²;

Suyeon Park, MS⁷;

Mark Loeb, MD⁸;

Tae Hyong Kim, MD¹

Author Affiliations

¹Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
²Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
³Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
⁴Department of Emergency Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
⁵Department of Family Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
⁶Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
⁷Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
⁸Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

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Key Points

Question Are there viral load differences between asymptomatic and symptomatic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?

Findings In this 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. The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients.

Meaning 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.

Abstract

Importance 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).

Objective To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients.

Design, Setting, and Participants A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea.

Main Outcomes and Measures Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care 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 8, 9, 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.

Results 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 (P = .07). 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 (β = −0.065 [SE, 0.023]; P = .005).

Conclusions and Relevance 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.

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Article Information

Accepted for Publication: June 29, 2020.

Corresponding Author: Eunjung Lee, MD, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagan-ro, Yongsan-gu, Seoul 14401, Republic of Korea (shegets@schmc.ac.kr).

Published Online: August 6, 2020. doi:10.1001/jamainternmed.2020.3862

Author Contributions: Dr E. Lee had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs S. Lee and T. Kim are joint first authors and contributed equally to the work.

Study concept and design: S. Lee, Tark Kim, E. Lee, H. Kim, J. Park, Choo.

Acquisition, analysis, or interpretation of data: S. Lee, Tark Kim, E. Lee, C. Lee, Rhee, Se Yoon Park, Son, Yu, Suyeon Park, Loeb, Tae Hyong Kim.

Drafting of the manuscript: S. Lee, Tark Kim, E. Lee, H. Kim.

Critical revision of the manuscript for important intellectual content: S. Lee, Tark Kim, E. Lee, C. Lee, Rhee, Se Yoon Park, Son, Yu, J. Park, Choo, Suyeon Park, Loeb, Tae Hyong Kim.

Statistical analysis: S. Lee, E. Lee, Suyeon Park.

Obtained funding: E. Lee.

Administrative, technical, or material support: S. Lee, E. Lee, C. Lee, H. Kim, J. Park.

Study supervision: S. Lee, Tark Kim, E. Lee, C. Lee, Rhee, Se Yoon Park, Son, Choo, Tae Hyong Kim.

Conflict of Interest Disclosures: Dr Loeb reported receiving grants and personal fees from Seqirus, personal fees and nonfinancial support from Sanofi, and personal fees from the World Health Organization and Pfizer outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by the Soonchunhyang University Research Fund.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.