key: cord-1051767-wv7uqswn
authors: Zhang, X.; Wang, J.
title: Deducing the Dose-response Relation for Coronaviruses from COVID-19, SARS and MERS Meta-analysis Results
date: 2020-06-26
journal: nan
DOI: 10.1101/2020.06.26.20140624
sha: 4580455d212ab42a172cd958b66676aa732d8cd7
doc_id: 1051767
cord_uid: wv7uqswn

The fundamental dose-response relation is still missing for better evaluating and controlling the transmission risk of COVID-19. A recent study by Chu et al. has indicated that the anticipated probability of viral infection is about 12.8% within 1 m and about 2.6% at further distance through a systematic review and meta-analysis. This important information provides us a unique opportunity to assess the dose-response relation of the viruses, if reasonable exposure dose could be estimated. Here we developed a simple framework to integrate the a priori dose-response relation for SARS-CoV based on mice experiments, and the recent data on infection risk and viral shedding, to shed light on the dose-response relation for human. The developed dose-response relation is an exponential function with a constant k in the range of 6.19E4 to 7.28E5 virus copies. The result mean that the infection risk caused by one virus copy in viral shedding is about 1.5E-6 to 1.6E-5. The developed dose-response relation provides a tool to quantify the magnitude of the infection risk.

probability of viral infection is about 12.8% within 1 m and about 2.6% at further distance through a 11 systematic review and meta-analysis. This important information provides us a unique opportunity to 12 assess the dose-response relation of the viruses, if reasonable exposure dose could be estimated. Here 13 we developed a simple framework to integrate the a priori dose-response relation for SARS-CoV based 14 on mice experiments, and the recent data on infection risk and viral shedding, to shed light on the dose-15 response relation for human. The developed dose-response relation is an exponential function with a 16 constant k in the range of 6.19×10 4 to 7.28×10 5 virus copies. The result mean that the infection risk 17 caused by one virus copy in viral shedding is about 1.5×10 −6 to 1.6×10 −5 . The developed dose-response 18 relation provides a tool to quantify the magnitude of the infection risk. 19 20 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 26, 2020. and k is the pathogen dependent parameter. With a little mathematics, we could derive that p ~ d/k, 39 when the infection risk is below 15%, with the difference between p and d/k smaller than 8%. We 40 assume that the exponential model remains applicable for the dose-response relation for human. An overall effective dilution rate is required to convert the viral shedding into the exposure dose at 49 various distances. The overall effective dilution rate should be a combination of various factors, e.g. 50 the dilution when the exhaled air is mixed with the ambient air and the possibility for the exposed 51 person to actually inhale the contaminated plume. The meta-analysis study 2 offered a plausible way 52 to estimate this factor. It was shown that the chance of viral infection decreased by about a factor of 5 53 from within 1 m (12.8%) to further distance (2.6%). According to the exponential model, the dose-54 response relation is nearly linear within the range of p < 15% (k is a constant), which suggests that the 55 viral shedding from an infected individual should also be effectively diluted by about the same 56 magnitude. "Further distance" is likely within 2 or 3 meters considering the confined indoor space, so 57 we use 5 times per meter as the effective dilution factor (fdilu) to estimate the exposure dose. It was 58 reported in the meta-analysis 2 that the duration of exposure varied from any duration to a minimum 59 of 1 h. Here we use 1 h as a representative duration (texpo), which is close to the total duration of close 60 contact between a nurse / health worker and a patient per day 7 . The exposure (virus copies) at further 61 distance was estimated as d =Evirus/(fdilu) texpo. The framework is kept as simple as possible to avoid unnecessary uncertainties. The developed dose-87 response relation provides a tool to quantify the magnitude of the infection risk and can be used in 88 model assessment of the infection risk in specific cases 11 . The meta-analysis and evidence based study 89 provide a new opportunity to estimate the human dose-response relation. In the future, the uncertainties 90 could be reduced by using new technology, e.g. personal IoT (internet of things) devices, to record the 91 distance, exposure duration, and environmental factors, which could greatly improve the quality of 92 exposure dose estimation and thus the dose-response relation. 93 94 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 26, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 26, 2020. . https://doi.org/10.1101/2020.06.26.20140624 doi: medRxiv preprint

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134 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted June 26, 2020. . https://doi.org/10.1101/2020.06.26.20140624 doi: medRxiv preprint