Dose-response Relation Deduced for Coronaviruses From Coronavirus Disease 2019, Severe Acute Respiratory Syndrome, and Middle East Respiratory Syndrome: Meta-analysis Results and its Application for Infection Risk Assessment of Aerosol Transmission

Xiaole Zhang, Jing Wang, Xiaole Zhang, Jing Wang

Abstract

Background: A comprehensive understanding of the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance to effectively control the spread of coronavirus disease 2019 (COVID-19). However, the fundamental dose-response relation is missing for evaluation of the infection risk.

Methods: We developed a simple framework to integrate the a priori dose-response relation for SARS-CoV-2 based on mice experiments, the recent data on infection risk from a meta-analysis, and respiratory virus shedding in exhaled breath to shed light on the dose-response relation for humans. The aerosol transmission infection risk was evaluated based on the dose-response model for a typical indoor environment.

Results: The developed dose-response relation is an exponential function with a constant k in the range of about 6.4 × 104 to 9.8 × 105 virus copies, which means that the infection risk caused by 1 virus copy in viral shedding is on the order of 10-6 to 10-5. The median infection risk via aerosol transmission with 1-hour exposure (10-6 to 10-4) was significantly lower than the risk caused by close contact (10-1) in a room with an area of 10 to 400 m2 with 1 infected individual in it and with a typical ventilation rate of 1 air change per hour.

Conclusions: The infection risk caused by aerosol transmission was significantly lower than the risk caused by close contact. It is still necessary to be cautious for the potential aerosol transmission risk in small rooms with prolonged exposure duration.

Keywords: COVID-19; SARS-CoV-2; dose-response relation; infection risk; quantitative microbial risk assessment.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Schematic diagram for deducing the dose-response relation and quantitative microbial risk assessment for typical indoor environment.
Figure 2.
Figure 2.
Results under the assumption of log-normal distribution of viral shedding log10(Evirus)~Normal(4, 0.5), with 40% positive viral shedding. A, The estimated dose-response relations based on different contribution levels (0.1, 0.25, 0.5, 0.75, and 1) of the airborne virus-laden particles to the total dose from both exposure to airborne viruses and contact transmission. The solid line is the dose-response relation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on mice experiments [3]. The stars are the dose-dependent response to infection with SARS-CoV-2 from the ferret model [19]. A conversion factor of 300 from plaque-forming units to virus copies was used based on a previous study on SARS-CoV-2 [18]. B, Viral shedding and exposure dose for 1 hour duration. Zero values are not shown in the figure.
Figure 3.
Figure 3.
Influences of room size and ventilation on the infection risk via aerosol transmission. A, Infection risk via aerosol transmission in rooms of various sizes with ventilation rates of 1 air change per hour and 1 infected individual for 1 hour exposure. B, Infection risk via aerosol transmission in a 100-m2 room with different ventilation rates for 1 hour exposure.

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Source: PubMed

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