key: cord-0306710-t1d3mxse authors: Ji, S.; Xiao, S.; Wang, H.; Lei, H. title: Slight increase in fomite route transmission risk of SARS-CoV-2 Omicron variant compared with the ancestral strain in households date: 2022-04-13 journal: nan DOI: 10.1101/2022.04.13.22273821 sha: 5ea4a14f428c9a1532766d067e94bc534a50f1ff doc_id: 306710 cord_uid: t1d3mxse The Omicron SARS-CoV-2 variant has become the dominant lineage worldwide, and experimental study had shown that SARS-CoV-2 Omicron variant was more stable on various environmental surfaces than ancestral strain. However, how the changes of stability on surfaces would influence the role of fomite route in SARS-CoV-2 transmission is still unknown. In this study, we modeled the Omicron and ancestral strain SARS-CoV-2 transmission within a household over 1-day period from multiple pathways, i.e., airborne, droplet and contact route. We assumed there were 2 adults and 1 child in the household, and one of the adults was infected with SARS-CoV-2. We assume a scenario of pre-/asymptomatic infection, i.e., SARS-CoV-2 was emitted by breathing and talking, and symptomatic infection, i.e., SARS-CoV-2 was emitted by breathing, talking, and coughing. In pre-/asymptomatic infection, all three routes contributed a role, contact route contribute most (37%-45%), followed by airborne route (34%-38%) and droplet route (21%-28%). In symptomatic infection, droplet route was the dominant pathway (48%-71%), followed by contact route (25%-42%), airborne route played a negligible role (<10%). In the contact route, indirect contact (fomite) route dominated (contributed more than 97%). Compared with ancestral strain, though the contribution of contact route increased in Omicron variant transmission, the increase was slight, from 25%-41% to 30%-45%. Since the first emergency of severe acute respiratory syndrome coronavirus 2 (SARS- (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint was first contested in July 2020 (Aboubakr et al., 2021; Katona et al., 2022) , with literature strengthening this argument in different settings. The Centers for Disease Control and Prevention (CDC) had stated at the time that "People can be infected with SARS-CoV-2 through contact with surfaces. However, based on available epidemiological data and studies of environmental transmission factors, surface transmission is not the main route by which SARS-CoV-2 spreads, and the risk is considered to be low." (CDC, 2020). The newly emerged Omicron SARS-CoV-2 variant was firstly identified on 19 November 2021 in South Africa (Viana et al., 2022) , and soon become the dominant lineage worldwide, suggesting its high transmissibility in humans. A recent structural study indicates its spike protein is more stable than the ancestral strain (Zeng et al., 2021) , and an experimental study had also shown that SARS-CoV-2 Omicron variant was more stable on various environmental surfaces (Chin et al., 2022) . And the transmission of SARS-CoV-2 Omicron via packaging had been reported during the past few months. However, how the changes of stability on surfaces would influence the dominant transmission route of SARS-CoV-2 Omicron is still unknown. The relative importance of different transmission routes certainly varied under different scenarios (Gao et al., 2021) . In this study, we considered a household environment since All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Given that the mean household size is 2.95 in China (China Statistical Yearbook 2019), and 2.52 in USA. Thus the household size was assumed to be 3, i.e. two parents and one child with age around 10-year-old. Since adults are more susceptible to SARS-CoV-2, and there is no gender difference in susceptibility to COVID-19 (WHO, 2020), thus one of the parents was assumed to be infected with SARS-CoV-2, and other two individuals were assumed to be susceptible to SARS-CoV-2. In this study, we modeled the infection risk of SARS-CoV-2 of two susceptible individuals during 1-day exposure in the household environment. For SARS-CoV-2 infected individuals, they shed viruses into the environment via respiratory activities, such as breathing, talking, coughing, and sneezing. Given that the proportion of asymptomatic/pre-symptomatic infection could reach 57.5% (Yanes-Lane et al., 2020). In this study, we considered the following two scenarios: 1) asymptomatic or presymptomatic infection, i.e. infected individuals shed viruses into the environment via breathing and talking. Breathing and talking for 2 minutes would expel 2.4× 10 and 7.1× 10 mL saliva, respectively. During asymptomatic or presymptomatic infection, we assumed that 49.5% and 49.5% of the exhaled droplets by the patient were partitioned to porous and non-porous surfaces, and the rest 1% deposited on the infector's hands. 2) symptomatic infection, i.e. infected individuals shed viruses into the environment via breathing, talking and coughing. And one cough would expel 0.17 mL saliva, and the cough frequency was 30 per hour. And during symptomatic infection, we assumed that 89% and 10% of the exhaled droplets by the patient were partitioned to porous and non-porous surfaces respectively (Mizukoshi et al., 2021) , since the patient would lie in bed most time. The rest 1% deposited on the infector's hands. Detailed size distribution of droplets from breathing, talking and coughing are in Supplementary Information Part 1. Given that the viral load in the nasopharyngeal swabs peaked, on average, 1 d before symptom onset, with values of 8∼9 log10 RNA copies per mL, and then decreased exponentially (Néant et al., 2021; All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Wyllie et al., 2020) . Thus, in this study, in asymptomatic or presymptomatic infection, the viral concentration in the droplets was set from 10 5 ∼10 9 RNA copies per mL, and in symptomatic infection, the viral concentration was set from 10 4 ∼10 8 RNA copies per mL. As a respiratory infection, SARS-CoV-2 could be transmitted by contact, droplet, fomites, airborne route, and possible feces-oral, bloodborne and intrauterine transmission (WHO, 2020). In this study, we considered the four major transmission routes, i.e., contact, droplet, fomites, and airborne route, and classified them into the following three categories: 1. The airborne route refers to direct inhalation of an infectious agent through small droplet nuclei, that is, the residue of large droplets containing microorganisms that have evaporated to an aerodynamic diameter of less than 10 microns (termed respirable) (Nicas and Jones, 2009 ). These respirable droplets can deposit in the respiratory tract. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint Denoted the concentration of droplet nuclei of radius r at time t in the room air be 퐶 (푟, 푡), 푇 is the exposure times of susceptible person in the household, then the exposure dose of susceptible person during 푇 exposure time could be calculated by equation (1): Where 푟 is the largest radius for airborne droplets, 푝 is the pulmonary ventilation rate. 푟 is the droplets' initial radius just after exhalation, and we assume that the final radius 푟 after complete evaporation is 푟 = 푟 /3 ( Where 퐿(푟 , 0) is the concentration of virus in the droplets with initial radius 푟 ; 푞 is the ventilation rate of the room; 푏 is the death rate of coronavirus in aerosol, 푉 is the room volume, and 푘푟 quantifies the deposition rate of droplets with particle size 푟 on the horizontal environmental surface. 퐺 (푟 ) is the generation rate of droplets with radius 푟 exhaled by the infector. Denoted the total amount of droplets generated by All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint the infector per hour to be 푁 , and the droplet size distribution to be 푓(푟 ), then there is 퐺 (푟 ) = 푁 푓(푟 ). At steady state ( Assume that the exposure time of susceptible individuals in droplet transmission route is 푇 . Then the exposure dose caused by inhalation is: Where 푟 is the maximum radius of inspirable droplets. 퐿(푟 , 푡) is the concentration of viable pathogens in the droplets with initial particle size 푟 at the time t after being exhaled. For small droplets with particle size less than 10 μm, they have evaporated completely before being inhaled by the susceptible person, so 퐿(푟 , 푡) =0.25퐿(푟 , 0), But for large droplets, they may not evaporate completely when being inhaled by the susceptible person, 퐿(푟 , 푡) is determined by its evaporation time and inhalation time All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint 9 of susceptible persons. Assume that Tm (s) is the traveling time (s) for the exhaled droplets from the source to reach a susceptible person a distance S away, 푡 (푟 ) is the evaporation time for the droplets with radius 푟 . There is The average interpersonal distance between two individuals (S) during talking was set as 0.81 m (Zhang et al., 2020). By assuming 1% of virus contained droplets exhaled by the infector depositing on infector's hands, the rate of virus deposition on the infector's hand 푆 is: Where 퐴 and 퐴 represent the area of infector (adult) 's hand and large particle size droplet deposition area, respectively. With the deposition of viruses on hands, viruses on hands also lose activation and removed by hand hygiene. Denoted the natural inactivation rate of the virus on hands to be h . And the hand hygiene frequency was assumed to be 푐 and the hand hygiene efficiency was assumed to be 푒 . Hand hygiene (푒 ) was considered to remove 90% of virus (Temime et al., 2009 ). In order All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint to represent the discrete nurse hand hygiene process in the continuous governing ordinary differential equations, we made the following translation . After each hand hygiene, only a fraction (1-푒 ) of viruses remains on hands. Hand hygiene occurs 푐 times per hour, and the time-average rate of pathogen removal due to hand hygiene is denoted by h . On average, there is 1- At the steady state, the amount of virus on the patient's hands 푛 is Where h is the natural inactivation rate of the virus on hands. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. (13): Where 푐 , is the contact rate on the mucous membrane of 푖th susceptible individual, 훼 , is the transmission efficiency of the virus from hand to mucous membranes, 퐴 , is the contact area between hands and mucous membranes of the 푖 th susceptible individual. The negative exponential dose-response model (Lei et al., 2018) was used to estimate the infection risk, which implies that a single particle can start an infection, all single All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Where Some parameters had uncertainties that could not be controlled by the scenario settings. Thus we performed the following sensitivity analysis of these uncertain parameters All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 1. To assess the impact of hand-to-surface contact rates on the results, the hand-tosurface contact frequency at 2/h and 4/h were set respectively, in the baseline, the handto-surface contact frequency was 3/h. The risks of each pathway and the overall risk depended on the virus concentration in saliva ( Figure 2 ). For ancestral and Omicron strain, under same conditions, the overall infection risk was close, a little higher for Omicron strain (Figure 2 ). This was mainly due to the assumption that ancestral and Omicron strain had same dose response rates. But Omicron variant would have higher dose response rates since Omicron variant had higher infectivity. With higher dose response rates, the infection risk of Omicron variant All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. When the infector was symptomatic, the infector produced much more droplets, since cough could produce much more droplets than breathing and speaking, but the virus concentration in the saliva was supposed to be lower. Thus the overall infection risk of two susceptible individuals by asymptomatic or presymptomatic infection was close to that by symptomatic infection. This suggested that asymptomatic or presymptomatic infection could contribute about 50% of the SARS-CoV-2 transmission. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. Figure 3 . For both strains, the dominant routes during asymptomatic or presymptomatic were different to that during symptomatic infection. When the infector was asymptomatic or presymptomatic, all three routes contributed a role in SARS-CoV-2 transmission (Figure 3A, 3B) . Contact route contribute most (37%-45%), followed by airborne route (34%-38%) and droplet route (21%-28%). When the infector was symptomatic, droplet route was the dominant pathway (48%-71%), followed by contact route (25%-42%). Airborne route played a negligible role (<10%). Compared with ancestral strain, though the role of contact route increased in Omicron variant transmission, the increase was slight (Figure 3 ). All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint (B) (C) All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint (D) We also explored the relative contributions of direct and indirect contact routes in contact transmission of SARS-CoV-2 ( Figure 4) . In contact transmission of SARS-CoV-2 in household, indirect contact route dominated. This may be mainly due to that the frequency of hand-to-environmental surfaces contact (3 times per hour) was much higher than the frequency of hand-to-hand contact (0.1-0.5 times per hour), and the hand hygiene frequency was 0.5 per hour, but the environmental surfaces were not cleaned, so the virus concentration on environmental surfaces was higher than these on the hands (Supplementary Information Part 3 Figure S5 ). And because of the relative higher hand-to-hand contact between the susceptible child and the infector, thus direct contact route contributed more in contact transmission of SARS-CoV-2 for the susceptible child ( Figure 4 ). All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (Jones, 2020; Mizukoshi et al., 2021) . In the animal experiment study, the absolute risk of airborne, droplet and overall risk are 0, 3/10 and 7/13 respectively, thus simply considering inclusion and exclusion of contact transmission, the estimated contribution of airborne, droplet and contact route could be 0%, 57% and 43% respectively. This tendency was consistent with the results when the infector was symptomatic. In the modelling studies by Jones (2020) and Mizukoshi et al. (2021) , they both considered the virus emission via coughing, and in the study by Jones (2020), the author even only considered the virus emission via coughing. Jones found that droplet and airborne routes predominated, contributing 35% and 57% respectively in hospital. Mizukoshi et al. (2021) found that airborne route was much less important than contact route and droplet route, only contributing 4%-10% in SARS-CoV-2 transmission in hospital. This was consistent with the results when the infector was symptomatic in this study. In addition, Mizukoshi et al. (2021) found that the role of droplet route decreased with the increase of virus concentration in saliva, contributing 65%-70% when the virus concentration was 10 1 -10 4 /mL, and 20%-46% when the virus concentration was 10 5 -10 8 /mL. When the virus concentration was low, the estimated contribution of contact route was consistent with the results in this study (67%-71%). But when the virus concentration was high, the estimated 20%-46% contributions were much lower than these in this study (48%-71%). The main reason could be that the estimated overall risk in the study by Mizukoshi et al. (2021) (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. In our study, we found that the role of contact route increased slightly in Omicron variant transmission, no more than 5%. Therefore, contact transmission is not enough to cause too much concern. In contrast, we found that with the increase of pre-/asymptomatic infections in Omicron strain transmission (Garrett et al., 2022) compared with ancestral strain, airborne route should gain more attention in SARS-CoV-2 transmission and prevention. When the infector was symptomatic, airborne route played a negligible role (<10%), but this pathway became important (34%-38%) when the infector was asymptomatic or presymptomatic. This study has several limitations. Firstly, the results depend on the model assumptions. For example, the relative contribution of droplet route was dependent on the emission of virus in respirable droplets and the exposure time of susceptible individuals. The hand hygiene frequency and the hand hygiene efficiency affected the results related to contact route. These parameters remain highly uncertain. To improve the accuracy of the model, it is desirable to update the data pertaining to SARS-CoV-2 in future studies. Secondly, it should be noted that the scenario we assume at home is relatively simple, we only considered the close contact distance of 0.81 m between two individuals, and contacts of infected and susceptible are only considered for 30 minutes of conversation. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint In reality, there will be more complex activities, such as dining together, that may increase the risk of droplet and contact route. In other public places such as shopping malls, restaurants, etc., the dominant route may be different, thus we would further study scenarios of the other settings in the future study. Last, the behavioral settings of the susceptible adult and the susceptible child are the same, however, children may touch more surfaces and wash their hands less often, which may lead to a higher risk of contact transmission in children. 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No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted April 13, 2022. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted April 13, 2022. ; https://doi.org/10.1101/2022.04.13.22273821 doi: medRxiv preprint