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    2 Comments for this article
    Viral copies significantly overestimates infection risk
    Richard Falk, No PhD | No Affiliation
    The use of viral RNA copies significantly overestimates infection risk. For a variety of reasons including the innate immune system, not all measured RNA will be in infectious virions. Furthermore, TCID50 measurement using Vero E6 cells do not account for the innate immune system of the recipient (i.e. the infectious dose may be greater than 1 TCID50).

    For SARS-CoV (original SARS from 2003), there were 360 RNA copies per PFU which is roughly 250 TCID50 (based on Poisson-based ln(2) = 0.693 TCID50/PFU) for cultured virus [ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322807/ ]. For SARS-CoV-2, hACE2 transgenic mice had both RNA
    copies/mL and TCID50/mL measured from lung samples at the viral load peak of 3 days past infection (in an infectious dose study) where 10^6.77 = 5,890,000 RNA copies/mL corresponded with 10^2.44 TCID50 / 100 µL = 2754 TCID50/mL implying 2140 RNA copies per TCID50 [ https://www.nature.com/articles/s41586-020-2312-y ]. These conversions result in 2 or 3 orders of magnitude reduction in infectiousness with respect to Vero E6 cell cultures.

    In addition, there is also a factor for the infectious dose which is not 1 TCID50. In the same transgenic mice study noted above, straddle challenge doses for inhaled aerosol showed no mice infected at 720 or lower TCID50 and all mice infected at 900 or higher TCID50. A maximum likelihood dose I calculated from the study data gives a 726 TCID60 estimate for 50% probability of infection. This is another factor of 2 to 3 orders of magnitude.

    Using the volume of droplets in the fine aerosol fraction combined with the presumed concentration of infectious virions does not result in enough to infect at the attack rates since in well-mixed enclosed environment outbreak events. Yet long-distance aerosol events are seen so there must be other factors. The infective dose in humans may be lower than found in the transgenic mice study and/or there may be concentration enhancement in the smaller aerosols and/or the counts and volumes of the finest aerosol fraction may be undercounted.
    Excellent Study
    John Murphy, MHSc PhD ROH CIH MACE | University of Toronto Dalla Lana School of Public Health
    A useful study that converges on the question of the range of infectious doses. It would be good to ascertain the relationship between virus concentrations in the fluid lining the bronchioles / alveoli and concentrations in sputum / oral fluid, in order to refine the modeled aerosol virus concentrations and infectious doses.
    Views 21,561
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    Original Investigation
    Occupational Health
    July 27, 2020

    Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019

    Author Affiliations
    • 1Swiss Centre for Occupational and Environmental Health, Winterthur, Switzerland
    • 2Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
    JAMA Netw Open. 2020;3(7):e2013807. doi:10.1001/jamanetworkopen.2020.13807
    Key Points español 中文 (chinese)

    Question  What is the estimated viral load released from an individual with coronavirus disease 2019 (COVID-19) by breathing and coughing, and what is the resulting concentration in a room?

    Findings  In this mathematical modeling study, breathing and coughing by a simulated individual with COVID-19 were estimated to release large numbers of viruses in a poorly ventilated room with a coughing person. However, the estimated infectious risk posed by a person with typical viral load who breathes normally was low, and only few people with very high viral load posed an infection risk in a poorly ventilated closed environment.

    Meaning  These results may partially explain the observed rates of transmission and suggest that there is a need for strict respiratory protection when people are in the same room with an individual with COVID-19.


    Importance  Individuals with asymptomatic or mild coronavirus disease 2019 (COVID-19) have been reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome coronavirus 2 has been found at very high concentrations in swab and sputum samples from such individuals.

    Objective  To estimate the virus levels released from individuals with asymptomatic to moderate COVID-19 into different aerosol sizes by normal breathing and coughing, and to determine what exposure could result from this in a room shared with such individuals.

    Design, Setting, and Participants  This mathematical modeling study combined the size-distribution of exhaled breath microdroplets for coughing and normal breathing with viral swab and sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. Viral data were obtained from studies published as of May 20, 2020. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m3, the size of a small office or medical examination room.

    Main Outcomes and Measures  Modeling was used to estimate the viral load emitted by individuals breathing normally or coughing, and the concentrations expected in the simulated room at different ventilation rates.

    Results  The mean estimated viral load in microdroplets emitted by simulated individuals while breathing regularly was 0.0000049 copies/cm3, with a range of 0.0000000049 to 0.637 copies/cm3. The corresponding estimates for simulated coughing individuals were a mean of 0.277 copies/cm3 per cough, with a range of 0.000277 to 36 030 copies/cm3 per cough. The estimated concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m3 from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m3.

    Conclusions and Relevance  In this modeling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies per cubic meter in a room with an individual with COVID-19 with a high viral load, depending on ventilation and microdroplet formation process. The estimated infectious risk posed by a person with typical viral load who breathes normally was low. The results suggest that only few people with very high viral load pose an infection risk in poorly ventilated closed environments. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same small room with an individual, whether symptomatic or not, especially for a prolonged period.