Virus shedding là gì

  • Brief Communication
  • Published: 15 April 2020

Temporal dynamics in viral shedding and transmissibility of COVID-19

  • Xi He1na1,
  • Eric H. Y. Lau ORCID: orcid.org/0000-0002-6688-96372na1,
  • Peng Wu2,
  • Xilong Deng1,
  • Jian Wang1,
  • Xinxin Hao2,
  • Yiu Chung Lau2,
  • Jessica Y. Wong2,
  • Yujuan Guan1,
  • Xinghua Tan1,
  • Xiaoneng Mo1,
  • Yanqing Chen1,
  • Baolin Liao1,
  • Weilie Chen1,
  • Fengyu Hu1,
  • Qing Zhang1,
  • Mingqiu Zhong1,
  • Yanrong Wu1,
  • Lingzhai Zhao1,
  • Fuchun Zhang1,
  • Benjamin J. Cowling ORCID: orcid.org/0000-0002-6297-71542na2,
  • Fang Li1na2 &
  • Gabriel M. Leung ORCID: orcid.org/0000-0002-2503-62832na2

Nature Medicine volume26,pages 672675 [2020]Cite this article

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Subjects

  • Disease prevention
  • Epidemiology
  • Infectious diseases
  • Public health

Matters Arising to this article was published on 17 August 2020

An Author Correction to this article was published on 07 August 2020

This article has been updated

Abstract

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infectorinfectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% [95% confidence interval, 3057%] of secondary cases were infected during the index cases presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

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Main

SARS-CoV-2, the causative agent of COVID-19, spreads efficiently, with a basic reproductive number of 2.2 to 2.5 determined in Wuhan1,2. The effectiveness of control measures depends on several key epidemiological parameters [Fig. 1a], including the serial interval [duration between symptom onsets of successive cases in a transmission chain] and the incubation period [time between infection and onset of symptoms]. Variation between individuals and transmission chains is summarized by the incubation period distribution and the serial interval distribution, respectively. If the observed mean serial interval is shorter than the observed mean incubation period, this indicates that a significant portion of transmission may have occurred before infected persons have developed symptoms. Significant presymptomatic transmission would probably reduce the effectiveness of control measures that are initiated by symptom onset, such as isolation, contact tracing and enhanced hygiene or use of face masks for symptomatic persons.

Fig. 1: Transmission of infectious diseases.

a, Schematic of the relation between different time periods in the transmission of infectious disease. b, Human-to-human transmission pairs of SAR-CoV-2 virus [N = 77]. We assumed a maximum exposure window of 21 days prior to symptom onset of the secondary cases. Detailed information on the transmission pairs and the source of information is summarized in Supplementary Tables 2 and 3. c, Estimated serial interval distribution [top], inferred infectiousness profile [middle] and assumed incubation period [bottom] of COVID-19.

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SARS [severe acute respiratory syndrome] was notable, because infectiousness increased around 710 days after symptom onset3,4. Onward transmission can be substantially reduced by containment measures such as isolation and quarantine [Fig. 1a]5. In contrast, influenza is characterized by increased infectiousness shortly around or even before symptom onset6.

In this study, we compared clinical data on virus shedding with separate epidemiologic data on incubation periods and serial intervals between cases in transmission chains, to draw inferences on infectiousness profiles.

Among 94 patients with laboratory-confirmed COVID-19 admitted to Guangzhou Eighth Peoples Hospital, 47/94 [50%] were male, the median age was 47 years and 61/93 [66%] were moderately ill [with fever and/or respiratory symptoms and radiographic evidence of pneumonia], but none were classified as severe or critical on hospital admission [Supplementary Table 1].

A total of 414 throat swabs were collected from these 94 patients, from symptom onset up to 32 days after onset. We detected high viral loads soon after symptom onset, which then gradually decreased towards the detection limit at about day 21. There was no obvious difference in viral loads across sex, age groups and disease severity [Fig. 2].

Fig. 2: Temporal patterns of viral shedding.

Viral load [threshold cycle [Ct] values] detected by RTPCR [PCR with reverse transcription] in throat swabs from patients infected with SARS-CoV-2 [N = 94], overall and stratified by disease severity, sex, age group and link to Hubei province. The detection limit was Ct = 40, which was used to indicate negative samples. The thick lines show the trend in viral load, using smoothing splines. We added some noise to the data points to avoid overlaps.

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Separately, based on 77 transmission pairs obtained from publicly available sources within and outside mainland China [Fig. 1b and Supplementary Table 2], the serial interval was estimated to have a mean of 5.8 days [95% confidence interval [CI], 4.86.8 days] and a median of 5.2 days [95% CI, 4.16.4 days] based on a fitted gamma distribution, with 7.6% negative serial intervals [Fig. 1c]. Assuming an incubation period distribution of mean 5.2 days from a separate study of early COVID-19 cases1, we inferred that infectiousness started from 12.3 days [95% CI, 5.917.0 days] before symptom onset and peaked at symptom onset [95% CI, 0.90.9 days] [Fig. 1c]. We further observed that only

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