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Peter Piot, MD, PhD, director of The London School of Hygiene and Tropical Medicine, is a legend in global health, having been involved in identification of HIV and Ebola virus in Africa. He was founding executive director of UNAIDS and Under Secretary-General of the United Nations from 1995 to 2008. He joins JAMA's Q&A series to discuss the global public health response to COVID-19 past,...

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    4 Comments for this article
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    Importance of personal protective measures of hygiene for COVID-19 prevention
    Khichar Shubhakaran, MD(Med), D.M(Neurology) | Senior Professor and head of department of Neurology, M D M Hospital,Dr. S.N Medical College, Jodhpur India-342003.
    A very nice study worth in the present pandemic which highlights the importance of personal protective measures. We see practically that once incidences diminish people try to forgo the hygienic measures to combat the disease.
    CONFLICT OF INTEREST: None Reported
    Assumptions
    Missy Brown, MPH Northumbria | NHS, Public Health Registrar
    Why have the author's made this assumption: 'We also made a baseline assumption that individuals with asymptomatic infections are on average 75% as infectious as those with symptomatic infections'?
    CONFLICT OF INTEREST: None Reported
    Reproducing example calculations
    Michal Figurski, PhD | University of Pennsylvania
    Trying to reproduce your "example calculations" from supplemental content I run into multiple errors.

    In the code to calculate prop_symptomatic there are 2 undefined functions. Possibly "p_inc" was renamed as "p_symp_onset" and "infectious_g" was renamed as "infectiousness daily", is that correct?

    However, "prop_never_symptomatic" is still missing definition. Can you please clarify?
    CONFLICT OF INTEREST: None Reported
    Comment from the authors regarding the relative infectivity of persons without symptoms
    Jay Butler, MD | CDC
    We very much appreciate the robust discussion on this paper. A number of commentators have asked about the base value for the infectiousness of persons without symptoms relative to those with symptoms. In the manuscript, we cite three relevant estimates based on data: (1) similar viral shedding (i.e. 100%) among symptomatic and never symptomatic infections (Lee et al., Reference 9), (2) estimates of 40-140% based on an estimated risk ratio 95% confidence interval of 0.69-2.37 for case contacts of symptomatic versus asymptomatic/presymptomatic (Chaw et al., Reference 15), and (3) a rapid review based on six studies that inferred an approximate range of 40-70% (Mc Evoy et al., Reference 16).

    A baseline assumption was necessary to show the effects of different values of relative infectiousness and the proportion of individuals who never develop symptoms. The 75% value was used for the baseline as it lies within the range of estimates described above. That 75% is just a reference point. For example, Figure 1D includes 8% of transmission from those who are never symptomatic. One example of that would be 10% never symptomatic with 75% relative infectiousness (described in the manuscript). Another example with the same result is 30% never symptomatic with 20% relative infectiousness. Substantially lower estimates of relative infectiousness can therefore be considered in both Figure 1D and Figure 2. Even with 0% infectiousness from never symptomatic individuals (highly unlikely), more than half of transmission still comes from presymptomatic indivduals if onset occurs around the time of peak infectiousness.
    CONFLICT OF INTEREST: None Reported
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    Original Investigation
    Infectious Diseases
    January 7, 2021

    SARS-CoV-2 Transmission From People Without COVID-19 Symptoms

    Author Affiliations
    • 1COVID-19 Response, US Centers for Disease Control and Prevention, Atlanta, Georgia
    • 2Office of the Deputy Directory for Infectious Diseases, US Centers for Disease Control and Prevention, Atlanta, Georgia
    JAMA Netw Open. 2021;4(1):e2035057. doi:10.1001/jamanetworkopen.2020.35057
    Key Points

    Question  What proportion of coronavirus disease 2019 (COVID-19) spread is associated with transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from persons with no symptoms?

    Findings  In this decision analytical model assessing multiple scenarios for the infectious period and the proportion of transmission from individuals who never have COVID-19 symptoms, transmission from asymptomatic individuals was estimated to account for more than half of all transmission.

    Meaning  The findings of this study suggest that the identification and isolation of persons with symptomatic COVID-19 alone will not control the ongoing spread of SARS-CoV-2.

    Abstract

    Importance  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of coronavirus disease 2019 (COVID-19), is readily transmitted person to person. Optimal control of COVID-19 depends on directing resources and health messaging to mitigation efforts that are most likely to prevent transmission, but the relative importance of such measures has been disputed.

    Objective  To assess the proportion of SARS-CoV-2 transmissions in the community that likely occur from persons without symptoms.

    Design, Setting, and Participants  This decision analytical model assessed the relative amount of transmission from presymptomatic, never symptomatic, and symptomatic individuals across a range of scenarios in which the proportion of transmission from people who never develop symptoms (ie, remain asymptomatic) and the infectious period were varied according to published best estimates. For all estimates, data from a meta-analysis was used to set the incubation period at a median of 5 days. The infectious period duration was maintained at 10 days, and peak infectiousness was varied between 3 and 7 days (−2 and +2 days relative to the median incubation period). The overall proportion of SARS-CoV-2 was varied between 0% and 70% to assess a wide range of possible proportions.

    Main Outcomes and Measures  Level of transmission of SARS-CoV-2 from presymptomatic, never symptomatic, and symptomatic individuals.

    Results  The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms.

    Conclusions and Relevance  In this decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods, transmission from asymptomatic individuals was estimated to account for more than half of all transmissions. In addition to identification and isolation of persons with symptomatic COVID-19, effective control of spread will require reducing the risk of transmission from people with infection who do not have symptoms. These findings suggest that measures such as wearing masks, hand hygiene, social distancing, and strategic testing of people who are not ill will be foundational to slowing the spread of COVID-19 until safe and effective vaccines are available and widely used.

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