Clinical Course and Viral Shedding Among Patients With SARS-CoV-2

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2. Jefferson THeneghan C.

https://www.cebm.net/study/clinical-course-and-viral-shedding-among-patients-with-sars-cov-2/

Published on August 12, 2020

Reference Lee S, Kim T, Lee E, et al. 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. JAMA Intern Med. Published online August 06, 2020.  2020
Study type
Country Korea
Setting Community isolation centre
Funding Details Soonchunhyang University Research Fund.
Transmission mode Droplets, viral load
Exposures

Bottom Line

Many SARS-CoV-2 infected people remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients. Isolation of infected persons should be performed regardless of symptoms.

Evidence Summary

The characteristics of the patients include:

  • 36% were asymptomatic at the time of isolation, but 19% developed symptoms in isolation (median time from diagnosis to symptoms kick off) was 15 days. 
  • 567 (30%) tests were performed on asymptomatic patients and 1,319 (70%) tests performed in pre/symptomatic patients. 
  • The mean (SD) number of tests was 6.4 (2.1) per person for the 89 asymptomatic patients and 6.2 (2.3) tests for the 214 symptomatic patients. 
  • The median (Standard error) time from diagnosis to first negative conversion was 17 (1.07) days in asymptomatic patients and 19.5 (0.63) days in pre/symptomatic. 
  • The Ct value dynamics of the RdRp gene from URT specimens showed that viral loads of pre/symptomatic patients tended to decrease more slowly in the time interaction trend than those of asymptomatic patients, the opposite was observed for env genes from LRT (sputum) specimens. 
  • There were no significant differences in Ct values of env and N genes and N genes, from LRT specimens between asymptomatic and pre/symptomatic patients.

What did they do?

The retrospective study described quantitatively SARS-CoV-2 molecular viral shedding in 303 asymptomatic and symptomatic patients (aged between 22-36) between March 6 and March 26, 2020. 

The participants were isolated in a community treatment center in Cheonan, Republic of Korea which had formerly been used as a dormitory. 92% of patients with confirmed COVID infection were isolated in solitary confinement, and 8% shared spaces with separate rooms (8%).

HCP were 8 physicians, 12 nurses, and 8 nurse assistants. Physicians did daily telephone symptom monitoring, body temperature twice daily and collection of specimens from patients nasopharynx and oropharynx swabs and sputum from the lower respiratory tract for SARS-CoV-2 were routinely tested on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays further samples were performed at the discretion of the physician.

Trained HCW took the specimens but the patient spat in a cup as instructed after an early morning gargle. Patients could be seen by a physician on demand. There was a clean zone where health care workers worked, separated from the patient zone and there was a negative-pressure container for a portable radiograph. Isolation was ended after two consecutive negative results 24 hours during 1.2 weeks in isolation. 

The RT-PCR probed for 3 genetic markers: envelope (env) gene, RNA-dependent RNA polymerase (RdRp) gene, and nucleocapsid protein (N) gene. The Ct cut off was 40.

Study reliability

The biggest limitation of the study is a lack of viral culture to check the relation between infectiousness and Ct values. This is even more important as both symptomatics and asymptomatics appear to have the same viral load (as indicated by CTs) and roughly equivalent duration of shedding but we cannot be sure that they are equally infectious.

Symptoms per se are an insufficient guide to infectiousness and positivity.
In addition the provenance and selection of patients is unclear, limiting the generalisability of results. The cohort was made up of young patients.

Clearly defined setting Demographic characteristics described Follow-up length was sufficient Transmission outcomes assessed Main biases are taken into consideration
Unclear Yes Yes Yes Unclear

What else should I consider?

About the authors

Carl Heneghan

Carl Heneghan

Carl is Professor of EBM & Director of CEBM at the University of Oxford. He is also a GP and tweets @carlheneghan. He has an active interest in discovering the truth behind health research findings

Tom Jefferson

Tom Jefferson

Tom Jefferson is a senior associate tutor and honorary research fellow, Centre for Evidence-Based Medicine, University of Oxford.