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 | Global Health | JAMA Internal Medicine | JAMA Network
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    4 Comments for this article
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    Saliva sampling as the gold standard method of RT-PCR test for transmissibility among pre-symptomatic or asymptomatic people
    Yasuharu Tokuda, MD, MPH | Muribushi Okinawa Center for Teaching Hospitals
    We read with interest the results by Lee S et al about 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 in both asymptomatic and symptomatic patients.1 One of the key issues to tackle COVID-19 is how best to test, trace and isolate asymptomatic or pre-symptomatic infections. In majority of these symptomless cases, sputum is absent, but predominant mode of transmission includes talking, shouting, and singing. In these circumstances, sampling among respiratory tract specimen should be used and saliva could likely to be a choice of sampling because it can be obtained by patients themselves and it can reduce infectious risk to a sampling personnel. When we deal with infected asymptomatic or pre-symptomatic infections, assessing instant transmissibility or infectiousness should be a major purpose of testing rather than clinically diagnosing COVID-19.2,3 A clinical gold standard testing for this purpose among asymptomatic or pre-symptomatic people should continue to be RT-PCR test using samples of nasopharyngeal, oropharyngeal or saliva and viral shedding on saliva should be compared in both asymptomatic and symptomatic patients.

    Yasuharu Tokuda, MD, MPH
    Muribushi Okinawa for Teaching Hospitals, Okinawa, Japan
    Kenji Shibuya, MD, DrPH
    King’s College London, London, UK
    Taro Kondo, MD
    Kondo Clinic, Tokyo, Japan

    References

    1. Lee Sea. 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 Internal Medicine. 2020.
    2. He X, Lau EH, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature medicine. 2020;26(5):672-675.
    3. Larremore DB, Wilder B, Lester E, et al. Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance. medRxiv. 2020.
    CONFLICT OF INTEREST: None Reported
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    regarding study interptation
    dheer singh meena, md resident doctor | rml hospital delhi
    In this article, differential negative conversion is compared with respect to three genes in asymptomatic and symptomatic patients so which gene should be used for diagnosis?  In upper respiratory tract samples, rdrp gene has low ct value and delayed clearing in symptomatic patients. In sputum sample, env gene has low ct value in asymptomatic patients.  So what is the net interpretation of this study? Which patients recover early?
    CONFLICT OF INTEREST: None Reported
    Good in theory, Difficult to put into practice!
    Arvind Joshi, MBBS MD; FCGP FAMS FICP. | Our Own Discussion Group
    Isolating an asymptomatic person who indeed is infected with SARS-CoV-2 may be difficult, nay IMPOSSIBLE!
    Simply because there may be no way, even to guess which apperently asymptomatic person my be infected.
    It may be practically impossible to trace all the people who might have come in contact with a proven SARS-CoV-2 infected person.
    All the same I greatly appreciate and value the research, the thought, the efforts and knowledge it has generated!

    -Arvind Joshi;
    MBBS, MD; FCGP, FAMS, FICP;
    Founder Convener and President:
    Our Own Discussion Group;
    602-C, Megh Apartments; Ganesh Peth Lane Dadar West; Mumbai Maharashtra State
    INDIA; PIN 400028;
    and Consulting Physician at:
    Ruchi Diagnostic Centre/Ruchi Clinical Laboratory,
    Sector 21, Kharghar, Maharashtra State INDIA PIN 410210.
    CONFLICT OF INTEREST: None Reported
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    PCR Data Reliability and Clarification
    Tae-Ho Hwang, PhD | Pusan National University
    According to Park et al. (reference 3 of this paper), CTC (community treatment center) housing was designated for out-of-hospital cohort treatment of COVID-19 infected patients with mild symptoms in Korea as a resource-saving strategy.

    In this paper, PCR assay was conducted in a population of 303 SARS-CoV-2 infected patients isolated in a CTC.  The authors suggest that addressing asymptomatic patients may be necessary to control the spread of SARS-CoV-2. However the WHO update "Transmission of COVID19 by asymptomatic cases (June 11, 2020)" states that “asymptomatically infected patients are much less likely to transmit the virus”.
    /> We raise questions regarding confirmed infection in asymptomatic patients measured by PCR in this study, focusing on figure 2 and 3. PCR assays were scheduled to be conducted on day 8, 9, 15 and 16 post-diagnosis, but there seems to be no corresponding data shown for day 8, and no positive cases in day 9 monitoring. Furthermore, under the assumption that initial isolation was determined by a preliminary PCR positive (Ct value < 40) test (laboratory-confirmed COVID-19), these baseline viral load data are also absent.
    The higher incidence of positive PCR tests appear in the time frame following the few tests on day 9 and 10, so taken with the lack of initial PCR test results in this paper, we would ask if there were any possibility for community infection, as all patients were living in the same CTC after being designated for isolation. It is notable that some patients in the same CTC had substantially high loads of SARS-CoV-2 virus (< 25 in Ct value). In addition, viral load level speculated by linear regression suggests there are values higher than Ct 40 which aren’t included in the figures. Care should be taken when PCR data is considered as a positive signal in > 35 Ct value, as reliability may be low especially in asymptomatic patients (https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.32.2001483).

    Ct value may be the only parameter to confirm SARS-CoV-2 infection in these 303 patients. Accordingly, can housing asymptomatic PCR-positive patients and other patients showing high viral load (< 25 in Ct) in the same CTC be justified?
    CONFLICT OF INTEREST: None Reported
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    Original Investigation
    August 6, 2020

    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

    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
    JAMA Intern Med. 2020;180(11):1447-1452. doi:10.1001/jamainternmed.2020.3862
    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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