key: cord-1001394-veeeggts authors: Li, Yuguo title: Hypothesis: SARS‐CoV‐2 transmission is predominated by the short‐range airborne route and exacerbated by poor ventilation date: 2021-05-18 journal: Indoor Air DOI: 10.1111/ina.12837 sha: 35d8ecbaf1f9d51addcdfe524d9740cd45df0584 doc_id: 1001394 cord_uid: veeeggts nan These three criteria for demonstrating airborne transmission of any respiratory infection due to expired aerosols, with respect to release, transport/dilution, inhalation, and subsequent infection, are similar to postulates 1-4 proposed by Gwaltney and Hendley. 3 However, they are difficult to assess, except in animal studies or human challenge studies, in which it is also difficult to separate inhalation exposure from droplet spray and short-range airborne route. A positive demonstration of these criteria in animal studies may not directly translate to humans, while human challenges are difficult to perform due to ethical considerations. In outbreaks with observed infections, direct evidence of these three criteria mostly disappears after the outbreak has been identified. • An outbreak occurred that could be directly attributed to the lack of ventilation air introduction into, and circulation within, an enclosed space. • The incidence of infection in susceptible hosts was inversely associated with the ventilation rate per person. • A disease outbreak occurred in an enclosed space, most likely due to air transport of infectious droplet nuclei over a distance greater than 2 m. Some studies have presented evidence that satisfies these lessstringent criteria for SARS-CoV-2 transmission, 7 suggesting that airborne transmission of SARS-CoV-2 is likely. Here, I propose a different approach to demonstrating that SARS-CoV-2 transmission is likely predominated by the short-range airborne route and that long-range airborne transmission is only opportunistic, that is, when ventilation is insufficient. Various combinations of the different transmission routes can be tested to explain the aforementioned phenomena. For example, we may first assume that the large-droplet route is responsible for the observed predominance of close-contact transmission (O1), while the airborne route is responsible for long-range infection events (O4), and other routes may exist in a non-predominant manner. This explanation seems to have been partly, although not explicitly, adopted by most health authorities. 1, 13 Can this assumed predominant combination of routes explain O2 and O3? Large-droplet transmission, by its nature, is driven by the initial momentum of the expired droplets (≥50 µm). These large droplets also tend to fall within a threshold distance, and do not follow the air flow, but they can also deposit on surfaces in their path, for example, the mucus membranes of those in front of the infected individual. The trajectories of these F I G U R E 1 The first four basic observed infection patterns in the COVID-19 pandemic (O1-O4) lead to the hypothesis (represented by the top off-centre circle) that the short-range airborne route is predominant, with long-range transmission as its continuation. Consequences are deduced from the hypothesis to explain each of the four basic observations (O1-O4). This hypothesis can also be used to deduce at least two predictions to explain phenomena P5 and P6. Modified from Li et al. 12 The green tick sign means that the specific observation can be explained by the hypothesis. Readers are invited to identify other major phenomena of SARS-CoV-2 transmission or use the hypothesis to predict other trends in the pandemic, to verify or reject our theory. This is shown by an empty "secondary observations or predictions" in the figure. This figure is drawn following a similar thinking process model of Einstein 8 large droplets over a short distance should not significantly differ between indoor and outdoor settings when the surrounding airflow is weak. Thus, the rare occurrence of outdoor transmission (O3) cannot be explained. Hence, large droplets are not supported as the predominant transmission route. A recent mechanistic study 14 also revealed that exposure to large droplets is insignificant, but shortrange airborne exposure dominates. There is also the possibility of predominant transmission via short-range surface-touch and opportunistic long-range fomite routes. The immediate surfaces of susceptible individuals, such as facial areas and clothing, can be recipients of large droplets exhaled by a nearby source patient. Humans also tend to frequently touch their own surfaces, which may lead to self-inoculation. This combination of surface-touch routes may explain O1 and O4, but it cannot explain the significant difference observed between indoor and outdoor infection risks when people are in close contact (O2 and O3). Our analyses cannot refute the existence of large-droplet and fomite routes. Rather, these two routes are also assumed to occur opportunistically and are not likely to be predominant as they could not explain the major observed phenomena (O1-O4) in SARS-CoV-2 transmission. Is there a single transmission route or a group of transmission routes that can explain all six observed phenomena? Let us examine how an ideal expired jet works. As a jet develops, its momentum conserves, while its flow rate increases due to entrainment, which leads to a reduction in air speed. Based on simple jet dilution theory, we find that at a distance of 75 times the mouth diameter (ie, 1.6 m if the mouth diameter is 20 mm), air in the jet consists of one portion of air from the mouth and 23 portions from the surrounding air, due to entrainment. Thus, the jet is diluted 24fold at 1.6 m. The concentration of expired aerosols in the jet air is a mixture of those in the expired airflow at the origin and those in the entrained surrounding air. In outdoor settings, the surrounding air is expected to be "clean." However, in a room, the concentration of Observations O1-O4 can, thus, lead to the hypothesis that the short-range airborne route is predominant, with long-range airborne as its continuation (Figure 1 ). This hypothesis agrees well with the expired jet dilution theory described above. At least two other phenomena can be predicted from the hypothesis. Infection seems to be minimized when the majority of the public wear a mask, that is, mass masking (P5). Indoor spaces with moderate or vigorous activity and/or loud speaking or singing, such as gyms, choirs, 7 and meatprocessing plants, have shown high infection rates (P6). One can predict that blockage of the expired jet of an infected individual would significantly minimize, or even eliminate, the short-range airborne route. With the additional filtration effect of masks, for both infected and susceptible individuals, mass masking should successfully inhibit transmission (P5), although leaked aerosols may lead to probable long-range airborne transmission. However, mask wearing by only a small fraction of the population would not be effective, as there is a good chance that some or most individuals were infected because they did not wear a mask. How do we explain the high infection risk in rooms with moderate or vigorous activity and/or loud speaking or singing (P6)? Vigorous activity results in 5-7 times larger exhalation flow rates than the number at rest. 16 Thus, an infected individual engaging in vigorous activity may release 5-7 times more droplets than an infected individual at rest, and a susceptible individual engaging in vigorous activity in the same room may inhale 5-7 times more droplets. Thus, the infection risk in a room with vigorous activity becomes 25-49 times higher than that in a room with individuals at rest or engaged in mild activity. I refer to this as the generation-inhalation double-multiplier effect, which makes inspiratory exposure to re- Figure 1 to predict other trends in the pandemic that we have not identified thus far, to verify or reject our theory. Currently, the WHO recognizes the possible role of airborne transmission in the spread of SARS-CoV-2 in special settings, but it has yet to recognize the likely predominance of the shortrange airborne route. Thus, the significant adverse effect of poor ventilation (≤3 L/s per person) on short-range airborne transmission has also not been recognized. Existing ventilation standards, such as ASHRAE 62.1, do not consider infection control as their objective. There is a need to develop a set of minimum ventilation rates for indoor spaces used for different activities. A home may have adequate ventilation for existing family members, but when relatives or friends visit, the occupancy situation changes and the ventilation may become inadequate. This may explain the significant number of outbreaks observed after family gatherings. 10 Ventilation is not usually considered as a parameter when choosing an indoor space for activities. As discussed earlier, in spaces used for moderate or vigorous activities, existing ventilation standards recommend much lower minimum ventilation rates than those required for infection control, due to the generationinhalation double-multiplier effect. The predominance of the short-range airborne route of SARS-CoV-2 transmission strongly suggests the need for healthcare workers who care for COVID-19 patients to wear an N95 mask. Ventilation rates can be enhanced in some buildings using simple strategies, such as changing fan settings or opening windows, but in many buildings, such improvements are not possible in the short term. In this case, determining the maximum occupancy may be possible by measuring the ventilation rates or using CO 2 monitoring to detect insufficient ventilation rates. However, the CO 2 monitoring method may not work well in situations where exhalation is not the only CO 2 source. Moreover, CO 2 monitoring cannot account for non-ventilation mechanisms for the removal of infectious aerosols, such as virus deactivation, deposition, and filtration. Strong coughing, loud talking, and singing are known to increase virus generation but may not necessarily have the same impact on CO2 generation. Nevertheless, monitoring ventilation rates using CO 2 warrants further investigation in the near future. COVID-19, long-range airborne transmission, SARS-CoV-2 transmission, short-range airborne transmission, ventilation Council via a General Research Fund project (no. 17202719) and a Collaborative Research Fund project (no. C7025-16G). There is no conflict of interest declared. The peer review history for this article is available at https://publo ns.com/publo n/10.1111/ina.12837. Coronavirus disease (COVID-19): How is it transmitted? Basic routes of transmission of respiratory pathogens -a new proposal for transmission categorisation based on respiratory spray, inhalation and touch. (Editorial). 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