Coronavirus Disease 2019 and Airborne Transmission: Science Rejected, Lives Lost. Can Society Do Better?

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.

Environmental Stability of Enveloped Viruses Is Impacted by Initial Volume and Evaporation Kinetics of Droplets.

Efficient spread of respiratory viruses requires the virus to maintain infectivity in the environment. Environmental stability of viruses can be influenced by many factors, including temperature and humidity. Our study measured the impact of initial droplet volume (50, 5, and 1 µL) and relative humidity (RH; 40%, 65%, and 85%) on the stability of influenza A virus, bacteriophage Phi6 (a common surrogate for enveloped viruses), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under a limited set of conditions. Our data suggest that the drying time required for the droplets to reach quasi-equilibrium (i.e., a plateau in mass) varied with RH and initial droplet volume. The macroscale physical characteristics of the droplets at quasi-equilibrium varied with RH but not with the initial droplet volume. Virus decay rates differed between the wet phase, while the droplets were still evaporating, and the dry phase. For Phi6, decay was faster in the wet phase than in the dry phase under most conditions. For H1N1pdm09, decay rates between the two phases were distinct and initial droplet volume had an effect on virus viability within 2 h. Importantly, we observed differences in virus decay characteristics by droplet size and virus. In general, influenza virus and SARS-CoV-2 decayed similarly, whereas Phi6 decayed more rapidly under certain conditions. Overall, this study suggests that virus decay in media is related to the extent of droplet evaporation, which is controlled by RH. Importantly, accurate assessment of transmission risk requires the use of physiologically relevant droplet volumes and careful consideration of the use of surrogates. IMPORTANCE During the COVID-19 pandemic, policy decisions were being driven by virus stability experiments with SARS-CoV-2 in different droplet volumes under various humidity conditions. Our study, the first of its kind, provides a model for the decay of multiple enveloped RNA viruses in cell culture medium deposited in 50-, 5-, and 1-µL droplets at 40%, 65%, and 85% RH over time. The results of our study indicate that determination of half-lives for emerging pathogens in large droplets may overestimate transmission risk for contaminated surfaces, as observed during the COVID-19 pandemic. Our study implicates the need for the use of physiologically relevant droplet sizes with use of relevant surrogates in addition to what is already known about the importance of physiologically relevant media for risk assessment of future emerging pathogens.

Airborne transmission of respiratory viruses including severe acute respiratory syndrome coronavirus 2.

PURPOSE OF REVIEW: The coronavirus disease 2019 pandemic has had a wide-ranging and profound impact on how we think about the transmission of respiratory viruses This review outlines the basis on which we should consider all respiratory viruses as aerosol-transmissible infections, in order to improve our control of these pathogens in both healthcare and community settings. RECENT FINDINGS: We present recent studies to support the aerosol transmission of severe acute respiratory syndrome coronavirus 2, and some older studies to demonstrate the aerosol transmissibility of other, more familiar seasonal respiratory viruses. SUMMARY: Current knowledge on how these respiratory viruses are transmitted, and the way we control their spread, is changing. We need to embrace these changes to improve the care of patients in hospitals and care homes including others who are vulnerable to severe disease in community settings.

What were the historical reasons for the resistance to recognizing airborne transmission during the COVID-19 pandemic?

The question of whether SARS-CoV-2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID-19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID-19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases.

An exploration of the political, social, economic and cultural factors affecting how different global regions initially reacted to the COVID-19 pandemic.

Responses to the early (February-July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the various pandemic restrictions, like masking, social distancing and self-isolation or self-quarantine. The degree of compliance with these measures depended on how much individuals valued their needs and liberties over those of their society. Thus, several themes may be relevant when comparing pandemic responses across different regions. East and Southeast Asian populations tended to be more collectivist and self-sacrificing, responding quickly to early signs of the pandemic and readily complied with most restrictions to control its spread. Australasian, Eastern European, Scandinavian, some Middle Eastern, African and South American countries also responded promptly by imposing restrictions of varying severity, due to concerns for their wider society, including for some, the fragility of their healthcare systems. Western European and North American countries, with well-resourced healthcare systems, initially reacted more slowly, partly in an effort to maintain their economies but also to delay imposing pandemic restrictions that limited the personal freedoms of their citizens.

Evidence for a semisolid phase state of aerosols and droplets relevant to the airborne and surface survival of pathogens.

The phase state of respiratory aerosols and droplets has been linked to the humidity-dependent survival of pathogens such as SARS-CoV-2. To inform strategies to mitigate the spread of infectious disease, it is thus necessary to understand the humidity-dependent phase changes associated with the particles in which pathogens are suspended. Here, we study phase changes of levitated aerosols and droplets composed of model respiratory compounds (salt and protein) and growth media (organic-inorganic mixtures commonly used in studies of pathogen survival) with decreasing relative humidity (RH). Efflorescence was suppressed in many particle compositions and thus unlikely to fully account for the humidity-dependent survival of viruses. Rather, we identify organic-based, semisolid phase states that form under equilibrium conditions at intermediate RH (45 to 80%). A higher-protein content causes particles to exist in a semisolid state under a wider range of RH conditions. Diffusion and, thus, disinfection kinetics are expected to be inhibited in these semisolid states. These observations suggest that organic-based, semisolid states are an important consideration to account for the recovery of virus viability at low RH observed in previous studies. We propose a mechanism in which the semisolid phase shields pathogens from inactivation by hindering the diffusion of solutes. This suggests that the exogenous lifetime of pathogens will depend, in part, on the organic composition of the carrier respiratory particle and thus its origin in the respiratory tract. Furthermore, this work highlights the importance of accounting for spatial heterogeneities and time-dependent changes in the properties of aerosols and droplets undergoing evaporation in studies of pathogen viability.

Airborne Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): What We Know.

We examine airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential using a source-to-dose framework beginning with generation of virus-containing droplets and aerosols and ending with virus deposition in the respiratory tract of susceptible individuals. By addressing 4 critical questions, we identify both gaps in addressing 4 critical questions with answers having policy implications.

Infectious SARS-CoV-2 Is Emitted in Aerosol Particles.

Respiratory viruses such as SARS-CoV-2 are transmitted in respiratory droplets and aerosol particles, which are released during talking, breathing, coughing, and sneezing. Noncontact transmission of SARS-CoV-2 has been demonstrated, suggesting transmission via virus carried through the air. Here, we demonstrate that golden Syrian hamsters produce infectious SARS-CoV-2 in aerosol particles prior to and concurrent with the onset of mild clinical signs of disease. The average emission rate in this study was 25 infectious virions/hour on days 1 and 2 postinoculation, with average viral RNA levels 200-fold higher than infectious virus in aerosol particles. The majority of virus was contained within particles <5 µm in size. Thus, we provide direct evidence that, in hamsters, SARS-CoV-2 is an airborne virus. IMPORTANCE SARS-CoV-2 is a respiratory virus and has been isolated from the air near COVID-19 patients. Here, using a hamster model of infection, we demonstrate that SARS-CoV-2 is emitted in aerosol particles prior to and concurrent with the onset of mild disease. Virus is contained primarily within aerosol particles <5 µm in size, which can remain airborne and be inhaled. These findings indicate that SARS-CoV-2 is an airborne virus and support the use of ventilation to reduce SARS-CoV-2 transmission.

Mechanistic theory predicts the effects of temperature and humidity on inactivation of SARS-CoV-2 and other enveloped viruses.

Ambient temperature and humidity strongly affect inactivation rates of enveloped viruses, but a mechanistic, quantitative theory of these effects has been elusive. We measure the stability of SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities (RH); median estimated virus half-life is >24 hr at 10°C and 40% RH, but ∼1.5 hr at 27°C and 65% RH. Our mechanistic model uses fundamental chemistry to explain why inactivation rate increases with increased temperature and shows a U-shaped dependence on RH. The model accurately predicts existing measurements of five different human coronaviruses, suggesting that shared mechanisms may affect stability for many viruses. The results indicate scenarios of high transmission risk, point to mitigation strategies, and advance the mechanistic study of virus transmission.

Airborne transmission of respiratory viruses.

The COVID-19 pandemic has revealed critical knowledge gaps in our understanding of and a need to update the traditional view of transmission pathways for respiratory viruses. The long-standing definitions of droplet and airborne transmission do not account for the mechanisms by which virus-laden respiratory droplets and aerosols travel through the air and lead to infection. In this Review, we discuss current evidence regarding the transmission of respiratory viruses by aerosols-how they are generated, transported, and deposited, as well as the factors affecting the relative contributions of droplet-spray deposition versus aerosol inhalation as modes of transmission. Improved understanding of aerosol transmission brought about by studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires a reevaluation of the major transmission pathways for other respiratory viruses, which will allow better-informed controls to reduce airborne transmission.

A Paradigm Shift to Align Transmission Routes With Mechanisms.

Current infection-control guidelines subscribe to a contact/droplet/airborne paradigm that is based on outdated understanding. Here, we propose to modify and align existing guidelines with a more accurate description of the different transmission routes. This will improve the effectiveness of control measures as more transmissible variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge.

Relative Humidity Predicts Day-to-Day Variations in COVID-19 Cases in the City of Buenos Aires.

Possible links between the transmission of COVID-19 and meteorology have been investigated by comparing positive cases across geographical regions or seasons. Little is known, however, about the degree to which environmental conditions modulate the daily dynamics of COVID-19 spread at a given location. One reason for this is that individual waves of the disease typically rise and decay too sharply, making it hard to isolate the contribution of meteorological cycles. To overcome this shortage, we here present a case study of the first wave of the outbreak in the city of Buenos Aires, which had a slow evolution of the caseload extending along most of 2020. We found that humidity plays a prominent role in modulating the variation of COVID-19 positive cases through a negative-slope linear relationship, with an optimal lag of 9 days between the meteorological observation and the positive case report. This relationship is specific to winter months, when relative humidity predicts up to half of the variance in positive case count. Our results provide a tool to anticipate possible local surges in COVID-19 cases after events of low humidity. More generally, they add to accumulating evidence pointing to dry air as a facilitator of COVID-19 transmission.

Correlating indoor and outdoor temperature and humidity in a sample of buildings in tropical climates.

The incidence of several respiratory viral infections has been shown to be related to climate. Because humans spend most of their time indoors, measures of indoor climate, rather than outdoor climate, may be better predictors of disease incidence and transmission. Therefore, understanding the relationship between indoor and outdoor climate will help illuminate their influence on the seasonality of diseases caused by respiratory viruses. Indoor-outdoor relationships between temperature and humidity have been documented in temperate regions, but little information is available for tropical regions, where seasonal patterns of respiratory viral diseases differ. We have examined indoor-outdoor correlations of temperature, relative humidity (RH), and absolute humidity (AH) over a 1-year period in each of seven tropical cities. Across all cities, the average monthly indoor temperature was 25 ± 3°C (mean ± standard deviation) with a range of 20-30°C. The average monthly indoor RH was 66 ± 9% with a range of 50-78%, and the average monthly indoor AH was 15 ± 3 g/m3 with a range of 10-23 g/m3 . Indoor AH and RH were linearly correlated with outdoor AH when the air conditioning (AC) was off, suggesting that outdoor AH may be a good proxy of indoor humidity in the absence of AC. All indoor measurements were more strongly correlated with outdoor measurements as distance from the equator increased. Such correlations were weaker during the wet season, especially when AC was in operation. These correlations will provide insight for assessing the seasonality of respiratory viral infections using outdoor climate data, which is more widely available than indoor data, even though transmission of these diseases mainly occurs indoors.