The long-standing dichotomy of droplets and aerosols
The COVID-19 pandemic has reawakened the long-standing dichotomy of respiratory droplets and aerosols in terms of their size and transmission distance [
47,
243]. Droplets and aerosols are erroneously seen as categorical transmission modes instead of a continuum of respiratory particles influenced by particle size and density, emission composition, turbulence and direction of the exhaled jet plume, and interacting environmental conditions [
48,
244]. Larger droplets (traditionally defined as >5–10 μm in diameter) stay aloft for shorter periods of time relative to their size, settle on the ground within seconds to minutes because of gravitational force, and are transmitted over short distances (usually < 6 ft or 2 m), although airflow can propel them farther across a room. Small-particle aerosols or droplet nuclei (traditionally defined as <5 μm) generally evaporate and disperse faster than they fall, remain in the air for minutes to hours, and travel longer distances. This outdated distinction between droplets and aerosols has been revised by aerosol scientists arguing that the correct size threshold to differentiate these particles should be 100–200 μm [
245‐
247]. “Aerosols,” a term commonly used as a shorthand for “aerosol particles,” are defined as a stable suspension of solid and/or liquid particles in air smaller than the above size cutoff, whereas droplets are defined as liquid particles larger than aerosols [
247].
SARS-CoV-2 transmission cannot be separated into the earlier dichotomy of stationary droplets vs. suspended aerosols or the newer dichotomy airborne vs. non-airborne. Transmission patterns are on a continuum rather than dichotomous [
48]. Although several issues need clarification and discussion to achieve scientific understanding and effective public communication, no debate exists as to whether respiratory particles of varying sizes can be generated from an individual. Both aerosol-generating behaviors (e.g., coughing, sneezing, speaking, singing, shouting, breathing) [
248‐
250] and medical aerosol-generating procedures (AGPs)
18 [
253] lead to the production of respiratory particles spanning a wide spectrum of sizes. To avoid dichotomization and better describe the behavior of respiratory particles, some researchers have referred to the continuum of aerosols and droplets of all sizes as a multiphase turbulent gas cloud (“puff”) of exhaled air [
244].
The modes of transmission of SARS-CoV-2
Transmission of SARS-CoV-2 may occur via several biologically plausible routes and depends on multiple factors, including the infectious dose (or inoculum), virus viability, exposure distance and duration, environmental factors (temperature, humidity, precipitation, pH, airflow/ventilation, solar ultraviolet radiation, chemicals), and host factors (breathing rate, respiratory tract morphology, target tissues, receptor distribution, host barriers and immune responses) [
49,
254‐
256]. Transmission risk in specific settings is further influenced by existing infection prevention and control (IPC) practices and public health interventions [
257,
258].
As acknowledged by the CDC, SARS-CoV-2 transmission occurs through three non-exclusive modes of exposure to infectious respiratory fluids: 1) inhalation of infectious small fine droplets and aerosol particles, 2) deposition of these particles onto mucous membranes (nose, mouth, or eyes), and 3) by touching mucous membranes with hands contaminated by respiratory fluids or indirectly by touching inanimate surfaces with virus on them [
50]. As transmission of infectious agents is complex and dependent on several factors, awareness of such distinctions is important for NPIs and public communication. Although the relative contribution of all transmission modes remains unquantified [
49], substantial evidence exists in support of specific transmission modes. Close-contact respiratory transmission, via short-range (inhalable) aerosols and droplets, is the primary mode of SARS-CoV-2 transmission [
48,
49]. Direct contact (physical) transmission and indirect contact transmission (or fomite transmission) play a minor role in propagating SARS-CoV-2 [
46,
51,
155,
259]. Long-range aerosol transmission (traditionally known as airborne transmission) occurs situationally, under certain conditions such as prolonged exposure in enclosed spaces with inadequate ventilation [
47,
50]. SARS-CoV-2 infections through inhalation at distances greater than 6 ft are less likely to occur than at close distances. The CDC has also emphasized that transmission due to inhalation and mucosal deposition of virus is effectively mitigated by existing intervention recommendations [
50], such as well-fitted masks, adequate ventilation, physical distancing, and avoidance of crowded indoor spaces. Other transmission routes (e.g., conjunctival, vertical, fecal-oral, zoonotic), though possible or suggested, are regarded as insignificant based on existing evidence [
46].
Airborne transmission—taken in its traditional definition of long-distance and respirable aerosols—is not the dominant or exclusive route for SARS-CoV-2 transmission [
48,
49]. Conflicting and polarizing messages pertaining to SARS-CoV-2 transmission modes jeopardize pandemic response plans, resulting in public unwillingness to adhere to risk reduction practices. Exaggerating the frequency of a transmission route [
260] prioritizes unnecessary IPC measures and social behaviors in hospital and community settings at the expense of effective interventions in place and undercuts public trust. Infectious disease transmission has important implications for deploying cost-effective IPC protocols and allocating resources to achieve the largest impact possible. Overstated evidence can lead to harmful policies. By amplifying findings from studies with methodological concerns and limited transferability of results [
261,
262], some academics and laypeople have advocated the use of filtering facepiece respirators (FFRs) in routine healthcare or even in community scenarios [
263‐
266], despite evidence showing that FFRs may not be necessary in some settings to reduce transmission risk [
267]. This has led to risk perception disparities and public confusion.
Epidemiological evidence
Epidemiological data (outbreak, cohort, and case-control studies) help determine SARS-CoV-2 transmission mechanisms in real-world conditions. Theoretical modeling, laboratory-based, and in silico studies are useful as complementary sources of knowledge but are not necessarily reflective of the frequency of a transmission mode and the real-life situations, especially if they do not consider SARS-CoV-2 infectivity or are simulated in vastly different scenarios.
Several arguments support transmission through close contact with the infectious source [
48,
50,
52]. First, the basic reproduction number
19 (R
0, 2–3) [
268,
269] and household secondary attack rates (generally 10%–20%) [
230‐
232] for SARS-CoV-2 are compatible with predominant close contact transmission rather than long-range aerosol transmission [
47,
270]. Second, several observational reports of COVID-19 hospital cases and outbreaks have indicated that transmission-based precautions (TBPs) for routine care of patients generally work if instituted timely and consistently [
48,
257,
271‐
284]. Hospital-acquired SARS-CoV-2 is rare in healthcare settings with robust IPC programs. The findings of some studies [
285,
286] reporting an increased risk for SARS-CoV-2 infection among healthcare workers (HCWs), even when wearing adequate PPE, compared to non-HCWs do not immediately translate into predominant long-range aerosol transmission, especially when there is little or no consideration of the variation in IPC practices and PPE types [
48], definitions of compliance and consistent wearing, AGP care exposure, breakroom or changing room exposure [
48,
287‐
289], and community SARS-CoV-2 exposure of HCWs [
290]. Medical masks have been demonstrated to reduce infectious titers of other respiratory viruses with similar transmission patterns [
291]. Meta-analyses of clinical studies comparing medical masks with FFRs have reported no statistically significant difference in preventing respiratory viral infections (including those caused by seasonal/endemic coronaviruses and influenza) in HCWs [
292‐
297]. The problem is that the evidence is heterogeneous and hindered by suboptimal PPE adherence and underpowered study designs. The need for higher-rated PPE should be calibrated to the degree of risk [
298]. As many HCWs in clinical care (and potentially other essential workers) are at the highest risk for exposure due to proximity, duration, and infectiousness of patients [
267], access to fit-tested FFRs is indicated for their safety. Medical masks reduce but do not eliminate aerosol exposure and therefore may offer incomplete protection for frontline HCWs and other HCWs that engage in near-range, face-to-face, sustained encounters with patients with known or suspected COVID-19, untested individuals, and/or individuals that are unable to wear masks [
298,
299]. The value of FFRs outside of these circumstances is likely marginal but more research is needed [
298]. Third, community-based reports generally support the effectiveness of the existing TBPs (if consistently and adequately instituted) [
300‐
309]. Accordingly, both the World Health Organization (WHO) and the CDC have reiterated that current recommendations are in general effective against both inhalation and mucosal deposition of respiratory particles [
50,
52].
Several SARS-CoV-2 outbreak studies have been published in different settings, including restaurants [
310,
311], call centers [
312], choir rehearsals [
313,
314], indoor fitness and sports facilities [
315‐
319], long-term care facilities [
201,
320‐
324], correctional facilities [
325], malls [
326], churches [
327,
328], flights [
304,
329], social gatherings [
330,
331], camps [
144], ships [
200,
303,
332], bus transportation [
333], and acute care hospital settings [
299,
334]. Many of these outbreak studies have been often cited by other reviews as evidence of airborne transmission. However, long-range aerosol transmission is a plausible explanation in only some of these settings [
48]. Other modes of transmission cannot be ruled out and may fit the particular transmission conditions. In general, published clusters associated with long-range aerosol transmission are singular events with preventable circumstances, such as prolonged duration of exposure, lapses in the use of PPE, increased exhalation, indoor settings, and poor ventilation.
Laboratory studies and modeling data
Different types of laboratory studies have been conducted in an attempt to elucidate SARS-CoV-2 transmission. Some laboratory studies (e.g., using a 3-jet Collison nebulizer) have shown that experimentally-generated SARS-CoV-2 aerosols may remain infectious for up to 3–16 hours [
335,
336]. Unfortunately, such studies under controlled laboratory conditions do not reflect physiological host processes and real-world environmental conditions related to viral transmission [
270,
337]. Respiratory particle transmission and viability over long distances are subject to changes in ambient temperature, relative humidity, airflow/ventilation, solar ultraviolet radiation (sunlight), and chemicals leading to evaporation, supersaturation, dilution, or inactivation [
49,
254‐
256]. Aerosol transmission, direct contact transmission, and fomite transmission have been experimentally demonstrated in multiple animal models [
49,
338‐
343]. Furthermore, studies in non-human primates, and confirmed in humans, demonstrate that infected individuals exhale infectious aerosols, but this is highly variable across individuals and activities [
344,
345].
Experimental, computational fluid dynamics simulation, and mathematical/numerical modeling studies have found that respiratory particles floating in the air can reach distances of 20–26 ft (6–8 m) or thereabouts [
244,
265,
346,
347]. However, this does not mean predominant long-range aerosol transmission of infectious viral particles. While respiratory particles have a great capacity to travel long distances or linger in the air for some time, transmission risk hinges greatly on how much infectious virus those particles contain and the conditions of the environment. These particles will diffuse and dilute in the surrounding air leading to progressively lower virus concentrations.
Droplet dispersion experiments (e.g., using laser light scattering) have shown that aerosols can travel for long distances [
265,
348‐
350]. However, these studies did not quantify infectious SARS-CoV-2 concentrations, which are likely substantially lower over long distances and under dynamic environmental conditions. Findings from Stadnytskyi et al. [
349] relied on the independent action hypothesis, which states that each virion has an equal, nonzero probability of causing an infection (i.e., even a single virion can establish infection). This hypothesis remains scarcely tested and is unknown to be valid for humans and their infecting viruses including SARS-CoV-2 [
270,
349].
Many studies have looked for evidence of viral RNA in ambient air samples and ventilation systems of hospitals [
351‐
385]. Some of these studies detected SARS-CoV-2 RNA in some air samples [
351‐
374], but other studies did not [
375‐
384]. Several of the qRT-PCR-positive studies were not successful in isolating viable SARS-CoV-2 [
351,
354,
357,
364,
366,
367,
371,
372], while others did not attempt to culture SARS-CoV-2 [
355,
356,
358‐
363,
365,
368‐
370,
373,
374]. Two hospital-based studies have reported infectious SARS-CoV-2 in ambient air. The study by Santarpia et al. collected aerosol samples around six patients admitted into medical wards, characterized the size distribution of aerosol particles, and assessed the presence of infectious virus in different particle size ranges in the patient environment [
352]. The authors demonstrated the presence of SARS-CoV-2 RNA and increases in viral RNA during cell culture of the virus from recovered aerosol samples, especially in particles with size < 1 μm. In another study, Lednicky et al. used an air sampling technology based on water vapor condensation to determine the presence of viable SARS-CoV-2 in hospital room air of two COVID-19 patients [
353]. Viable SARS-CoV-2 was isolated from air samples collected 2 to 4.8 m away from the patients, with estimates ranging from 6 to 74 median tissue culture infectious dose (TCID
50) per L of air. It is yet unclear the extent to which these findings represent an unmitigated risk in healthcare settings where PPE and other TBPs are properly applied. Identification of SARS-CoV-2 RNA and viable SARS-CoV-2 in air samples from healthcare settings lend credence for aerosol transmission in these settings but does not provide straightforward information on its frequency as a transmission mode for SARS-CoV-2. Nor is a hospital setting, with robust ventilation, air filtration, and PPE, comparable to risk or frequency in the community [
257]. This similarly applies to fomite transmission, which is not considered a major transmission mode despite numerous laboratory-based studies conducting environmental sampling and reporting SARS-CoV-2 surface contamination and stability [
386]. Nuance is needed when examining the evidence of air sampling studies instead of calling the retrieval of infectious SARS-CoV-2 a “smoking gun” [
387].
Some studies conducting community-based SARS-CoV-2 RNA detection in air samples have reported negative findings, including those from cruise ship cabins [
388], quarantined households [
389], residential areas [
354,
370], open public areas [
354,
368], and transportation [
368,
390]. In contrast, other studies have reported positive qRT-PCR-positive air samples from a variety of indoor or crowded public spaces [
370,
391] and transportation [
391,
392], with SARS-CoV-2 viability not assessed. Three additional studies assessing the presence of SARS-CoV-2 RNA in outdoor particulate matter (PM) in Italy and Spain found all air samples negative [
393‐
395]. A modeling study estimated a very low average outdoor concentration of SARS-CoV-2 RNA (<1 RNA copy/m
3) in uncrowded outdoor public areas in Italy, even in the worst-case scenario [
396]. Conversely, researchers of one Italian study found that 20 out of 34 PM
10 (PM with diameter < 10 μm) samples were qRT-PCR-positive [
397]; however, concentrations of virus-laden particles were not examined and culture data were not provided. Although the implications of atmospheric pollutants on transmission remain elusive [
53,
398], several studies (mostly ecological) and commentaries arguing about an association between air pollution and SARS-CoV-2 airborne transmission and mortality [
347,
399‐
404] have sparked concern about PM acting as a carrier of SARS-CoV-2 and diffusing the virus in open environments. An ecological study about PM in several Italian provinces found a positive correlation between daily PM
10 exceedances and COVID-19 cases [
403]. The authors of this study hypothesized that the growth and severity of cases in Milan could be attributed to airborne diffusion and a “boost effect on the viral infectivity corresponding to the peaks of PM.” They also illustrated the “airborne route of transmission as a ‘highway’ enhancing viral transmission over 8 m.” No scientific evidence suggests or supports such claims. Available air pollution studies point to correlation rather than causation (i.e., highly polluted areas in some countries are characterized by large populations and increased rates of human interaction, and lockdowns reduce both air pollution and SARS-CoV-2 spread) [
53,
398]. Furthermore, upon theoretical examination, the probability that atmospheric pre-existing PM scavenges virus aerosols is low [
396]. Monitoring of SARS-CoV-2 RNA in outdoor PM is therefore unlikely to be an early suitable indicator of viral diffusion or pandemic recurrence [
393,
394]. Some scientists have also speculated that airborne pollen [
405] and sea spray [
131,
132] may act as a modulating factor of SARS-2 infection and transmission, with only ecological data supporting an association for the former [
406]. However, there is enormous potential for confounding due to several factors implicated in transmission of respiratory viruses, including well-known environmental factors such as ambient temperature. In addition, no evidence supports that pollen grains are carriers of SARS-CoV-2, much less does it provide information on their frequency and risk of transmission. A study of air samples collected in Germany and experiments to examine potential complexes between purified pollen of various taxa and SARS-CoV-2 reported negative findings—in terms of both viral RNA and virus-induced cytopathic effects [
407]. While environmental exposome deserves further examination, evidence must be accurately communicated to avoid panic and misunderstandings.
In summary, a low level of air contamination has been demonstrated in both healthcare and non-healthcare settings thus far. The findings of the air sampling studies are related to the sampling methods and duration, storage and transferring conditions, the environmental setting, low viral concentrations, dilution effects, and ongoing IPC measures [
408,
409]. Further, pressing issues concerning virological testing warrant discussion. qRT-PCR cycle threshold (Ct) values have been increasingly used as informative proxies for probable infectivity [
196,
197,
410,
411]. However, viral nucleic acid detection by qRT-PCR-based assays does not equate to shedding of infectious, viable, culturable, or replication-competent virions [
412,
413]. Viral load and Ct values have limitations [
222,
414,
415]; their correlation depends on the gene targets used, the nucleic acid extraction system, among other factors. Detectable viral RNA exceeds infectious viral clearance [
43,
44,
194‐
197] likely because genomic and subgenomic RNA persists as residual viral fragments or is protected by cellular membranes, and degrades slowly after the immune system has neutralized or lysed virions [
412,
416]. Demonstrating virus amplification or cytopathic effect in cell culture, or virus quantification by plaque assays or TCID
50 endpoint dilution assays are needed to infer viral replication and infectious virus [
417]. Therefore, these are better surrogates for assessing transmission competency, although the sensitivity of viral culture may be a concern as well [
222]. Unfortunately, infectious titer assays must be conducted in biosafety level 3 (BSL-3) containment, so routine measurement of infectious SARS-CoV-2 in clinical settings cannot be done. Further methods to quantify infectiousness [
415] and reproducible research with emerging technologies to sample air particles are needed.
The use of the term “airborne,” the lack of nuance, and inaccurate analogies
It has become clear that aerosol transmission is an important transmission mode. However, there is controversy about using the term “airborne” due to varied existing definitions, meanings, and implications [
418], including the ordinary meaning of the word (carried in the air) and scientific conventions and specialized meanings referring to long-distance aerosol-based transmission.
While some scientists advocate the use of the term “airborne” as a simple term to use in risk communication with the public, the plain usage of this word when referring to SARS-CoV-2 transmission is technically reductionist and ambiguous. The flagrant use of the term “airborne” without providing nuance can be misinterpreted. For example, if the public wrongly believes that transmission occurs overwhelmingly from aerosols over an extended distance and time, they may reject guidance to wear medical masks or cloth face coverings (given their limited aerosol filtering efficiency in comparison with other facepieces), hoard FFRs, or feel that distancing precautions are futile. Likewise, if the public believes that the virus spreads extensively in the outdoor air and travels down blocks or across buildings, this may lead to potentially dangerous practices such as closing all windows in residential areas.
From a public health standpoint, the term “airborne” is not actionable on its own because it offers no clear guidance on how to curtail exposure risk. Simplistic messages and press article headlines, such as “The coronavirus is airborne,” "It is in the air,” and “Coastal breezes likely carry coronavirus” [
131,
132,
419‐
422] require nuance to provide effective and accurate risk communication in public health and to avoid misunderstandings of viral transmission and airborne fearmongering. This has been exacerbated by scientific commentaries claiming with selective citations that airborne transmission is the predominant mode of SARS-CoV-2 transmission, without addressing terminology, practical implications, and critical aspects in public health risk communication and community engagement [
260,
423]. Miscommunication of transmission modes precludes harm reduction approaches (e.g., enjoying outdoor spaces such as beaches [
132], and avoiding indoor gatherings) by failing to acknowledge that outdoor airborne transmission is low, particularly if the setting is uncrowded [
40,
138,
139].
Inaccurate analogies have also been increasingly used. Cigarette smoke has been mentioned as a proxy for SARS-CoV-2 infection risk [
216]. While this may meet the physical properties for aerosol scientists, analogies that intertwine sensory reception, such as smelling volatile organic compounds in smoke, can be misleading in terms of respiratory protection efficacy. The possibility to smell a vapor while wearing a fitted N95 FFR (or equivalent PPE) can mislead HCWs into thinking that their PPE is not effective.
Toward a multidisciplinary agreement on actionable terminology
Given the societal challenges of COVID-19, never has there been greater need for meaningful interdisciplinary dialogue. Agreement on actionable terminology that respects different fields is long overdue. The pandemic has underscored the continuum and spectrum that is viral transmission. Such complexities should be addressed with collaborative efforts to communicate in a way that meets the needs of all parties. Nuance and complexity can be understood by the public if communicated clearly and transparently. Public health messaging and risk communication should mention that respiratory pathogens may transmit over long distances via the air under specific conditions, while making clear recommendations about effective mitigation measures. Central to the use of accurate terminology is the risk assessment of indoor vs. outdoor spaces and banishing the thinking of viral transmission as miasma or an insidious trail containing endless infectious virions.
Rather than droplet vs. aerosol or airborne vs. non-airborne dichotomies, evolving terminology and science communication for respiratory pathogens should move toward reflecting the nuance of transmission and effective interventions [
48]. Broadening the “airborne” definition to inhalable aerosol/droplet exposure or respiratory transmission allows new avenues to be explored and reconciles seemingly contradictory data and disciplines. Furthermore, discussing enhanced respiratory precautions and differences between long- and short-range, as well as risk in terms of types of exposure and activities can effectively inform subsequent public health interventions. As long-range aerosol transmission is situational, these circumstances can be explained through an increase in risk factors as dimmers rather than on/off switches. Both the WHO and the CDC have utilized this approach with communicating risk, with an emphasis on proximity, activity, environment, ventilation, NPIs, and vaccination status [
32,
50,
52,
55,
424].
Bridging the interdisciplinary communication barriers and disagreements between the medical and engineering fields has proven complicated. Although academic disagreements may be valid and should not be met with hostility, narratives of misinformation and false dichotomies cause harm or do little to address the global needs for COVID-19 mitigation. There have been large-scale, continued attacks on those working in public health, which undermines public trust and is counterproductive to the pandemic response. Different disciplines should work together [
425], instead of taking an adversarial position against public health agencies like the WHO and the CDC [
426,
427], which is decidedly not constructive.
In the end, the unresolved semantic dilemma warrants interdisciplinary efforts from the full range of experts, including medicine, epidemiology, occupational hygiene, engineering, and fluid physics, seeking a classification framework that recognizes both technical knowledge and practical implications in the context of public health and reconciles with real-life evidence without drawing inaccurate or unduly alarmist conclusions from available studies. Nuanced and transparent communication efforts, coming from those actively working to advance health and research amid the pandemic and facing the challenges of media representation of terminology, are valuable endeavors.