Recognition of aerosol transmission of infectious agents: A commentary

Abstract

Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions that are required.
The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term to mean either large droplet or aerosol transmission.
However, these terms are often used confusingly when discussing specific infection control interventions for individual pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at an N95 rather than surgical mask level requirement.
With this in mind, this review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.

Full text

R E V I E W Open Access
Recognition of aerosol transmission of
infectious agents: a commentary
Raymond Tellier
1
, Yuguo Li
2
, Benjamin J. Cowling
3
and Julian W. Tang
4,5*
Abstract
Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether
the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions
that are required.
The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne
transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term
to mean either large droplet or aerosol transmission.
However, these terms are often used confusingly when discussing specific infection control interventions for individual
pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and
chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal
protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at
an N95 rather than surgical mask level requirement.
With this in mind, this review considers the commonly used term of ‘aerosol transmission’in the context of some infectious
agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus,
where the potential for airborne transmission is much more dependent on various host, viral and environmental factors,
and where its potential for aerosol transmission may be underestimated.
Keywords: Aerosol, Airborne, Droplet, Transmission, Infection
* Correspondence: julian.tang@uhl-tr.nhs.uk;jwtang49@hotmail.com
4
Department of Infection, Immunity and Inflammation, University of
Leicester, Leicester, UK
5
Clinical Microbiology, University Hospitals of Leicester NHS Trust, Level 5
Sandringham Building, Leicester Royal Infirmary, Infirmary Square, Leicester
LE1 5WW, UK
Full list of author information is available at the end of the article
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Tellier et al. BMC Infectious Diseases (2019) 19:101
https://doi.org/10.1186/s12879-019-3707-y
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Background
The classification of an infectious agent as airborne and
therefore ‘aerosol-transmissible’has significant implica-
tions for how healthcare workers (HCWs) need to manage
patients infected with such agents and what sort of per-
sonal protective equipment (PPE) they will need to wear.
Such PPE is usually more costly for airborne agents (i.e.
aerosol-transmissible) than for those that are only trans-
mitted by large droplets or direct contact because of two
key properties of aerosols: a) their propensity to follow air
flows, which requires a tight seal of the PPE around the
airways, and b) for bioaerosols, their small size, which calls
for an enhanced filtering capacity.
Several recent articles and/or guidance, based on clinical
and epidemiological data, have highlighted the potential for
aerosol transmission for Middle-East Respiratory Syndro
me-associated coronavirus (MERS-CoV) [1,2] and Ebola
virus [3,4]. Some responses to the latter have attempted to
put these theoretical risks in a more practical light [4], and
this nicely illustrates the quandary of how to classify such
emerging or re-emerging pathogens into either the large
droplet (short-range) versus airborne (short and possibly
long-range) transmission categories. However, this delinea-
tion is not black and white, as there is also the potential for
pathogens under both classifications to be potentially
transmitted by aerosols between people at close range (i.e.
within 1 m).
Definitions
Strictly speaking, ‘aerosols’refer to particles in suspension
in a gas, such as small droplets in air. There have been nu-
merous publications classifying droplets using particle sizes
over the years [5–10]. For example it is generally accepted
that: i) small particles of < 5–10 μm aerodynamic diameter
that follow airflow streamlines are potentially capable of
short and long range transmission; particles of < 5 μm
readily penetrates the airways all the way down to the al-
veolar space, and particles of < 10 μm readily penetrates
below the glottis (7) ii) large droplets of diameters > 20 μm
refer to those that follow a more ballistic trajectory (i.e.
falling mostly under the influence of gravity), where the
droplets are too large to follow inhalation airflow stream-
lines. For these particle sizes, for example, surgical masks
wouldbeeffective,astheywillactasadirectphysicalbar-
rier to droplets of this size that are too large to be inhaled
into the respiratory tract around the sides of the mask
(which are not close-fitting); iii) ‘intermediate particles’of
diameters 10–20 μm, will share some properties of both
small and large droplets, to some extent, but settle more
quickly than particles < 10 μm and potentially carry a
smaller infectious dose than large (> 20 μm) droplets.
‘Aerosols’would also include ‘droplet nuclei’which are
small particles with an aerodynamic diameter of 10 μm
or less, typically produced through the process of rapid
desiccation of exhaled respiratory droplets [5,6]. How-
ever, in some situations, such as where there are strong
ambient air cross-flows, for example, larger droplets can
behave like aerosols with the potential to transmit infec-
tion via this route (see next section below).
Several properties can be inferred from this, for example
the penetration of the lower respiratory tract (LRT), as at
greater than 10 μm diameter, penetration below the glottis
rapidly diminishes, as does any potential for initiating an
infection at that site. Similarly, any such potential for
depositing and initiating an LRT infection is less likely
above a droplet diameter of 20 μm, as such large particles
will probably impact onto respiratory epithelial mucosal
surfaces or be trapped by cilia before reaching the LRT [6].
The Infectious Diseases Society of America (IDSA) has
proposed a scheme that is essentially equivalent [7], defin-
ing “respirable particles”as having a diameter of 10 μmor
less; and “inspirable particles”as having a diameter between
10 μma
nd100μm, nearly all of which are deposited in the
upper airways. Some authors have proposed the term “fine
aerosols”, consisting of particles of 5 μm or less, but this
has been in part dictated by constraints from measurement
instruments [8]. Several authors lump together transmis-
sion by either large droplets or aerosol-sized particles as
“airborne transmission”[9], or use “aerosol transmission”
to describe pathogens that can causediseaseviainspirable
particles of any size [10].
However, we think that it is important to maintain a
distinction between particles of < 10 μm and larger parti-
cles, because of their significant qualitative differences
including suspension time, penetration of different re-
gions of the airways and requirements for different PPE.
In this commentary, we use the common convention of
“airborne transmission”to mean transmission by
aerosol-size particles of < 10 μm.
If the infected patients produce infectious droplets of
varying sizes by breathing, coughing or sneezing, trans-
mission between individuals by both short-range large
droplets and airborne small droplet nuclei are both pos-
sible, depending on the distance from the patient source.
Figure 1illustrates these potential routes of short and
long-range airborne transmission, as well as the down-
stream settling of such droplets onto surfaces (fomites).
From such fomites, they may be touched and transported
by hands to be self-inoculated into mucosal membranes
e.g. in the eyes, nose and mouth) to cause infection,
depending on the survival characteristics of individual
pathogens on such surfaces, and the susceptibility (related
to available, compatible cell receptors) of the different
exposed tissues to infection by these pathogens.
For example, when the infectious dose (the number of
infectious agents required to cause disease) of an organ-
ism is low, and where large numbers of pathogen-laden
droplets are produced in crowded conditions with poor
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ventilation (in hospital waiting rooms, in lecture theatres,
on public transport, etc.), explosive outbreaks can still
occur, even with pathogens whose airborne transmission
capacity is controversial, e.g. the spread of influenza in a
grounded plane where multiple secondary cases were
observed in the absence of any ventilation [11].
The more mechanistic approaches (i.e. arguing from the
more fundamental physical and dynamic behavior of small
versus larger particle and droplet sizes in the absence of
any biological interactions) to classifying which pathogens
are likely to transmit via the airborne route have been
published in various ways over the years [12–17], but may
have to be considered in combination with epidemiological
and environmental data to make a convincing argument
about the potential for the airborne transmissibility of any
particular agent –and the number of possible potential
exposure scenarios is virtually unlimited).
The importance of ambient airflows and the of aerosols
Oneshouldnotethat“aerosol”is essentially a relative and
not an absolute term. A larger droplet can remain airborne
for longer if ambient airflows can sustain this suspension
for longer, e.g. in some strong cross-flow or natural ventila-
tion environments, where ventilation-induced airflows can
propagate suspended pathogens effectively enough to cause
infection at a considerable distance away from the source.
One of the standard rules (Stoke’s Law) applied in
engineering calculations to estimate the suspension
times of droplets falling under gravity with air resist-
ance, was derived assuming several conditions includ-
ing that the ambient air is still [13–17]. So actual
suspension times will be far higher where there are
significant cross-flows, which is often the case in
healthcare environments, e.g. with doors opening, bed
and equipment movement, and people walking back
and forth, constantly. Conversely, suspension times,
even for smaller droplet nuclei, can be greatly re-
duced if they encounter a significant downdraft (e.g.
if they pass under a ceiling supply vent). In addition,
the degree of airway penetration, for different particle
sizes, also depends on the flow rate.
In the field of dentistry and orthopedics, where
high-powered electric tools are used, even bloodborne
viruses (such as human immunodeficiency virus –HIV,
hepatitis B and hepatitis B viruses) can become airborne
when they are contained in high velocity blood splatter
generated by these instruments [18,19]. Yet, whether they
can cause efficient transmission via this route is more
debatable. This illustrates another point, that although
some pathogens can be airborne in certain situations, they
may not necessarily transmit infection and cause disease
via this route.
Fig. 1 An illustration of various possible transmission routes of respiratory infection between an infected and a susceptible individual. Both close
range (i.e. conversational) airborne transmission and longer range (over several meters) transmission routes are illustrated here. The orange head
colour represents a source and the white head colour a potential recipient (with the bottom right panel indicating that both heads are potential
recipients via self-inoculation from contaminated surface fomite sources). Here ‘Expiration’also includes normal breathing exhalation, as well as
coughing and/or sneezing airflows. Airborne droplets can then settle on surfaces (fomites) from where they can be touched and carried on
hands leading to further self-inoculation routes of transmission
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Outline
Over time, for a pathogen with a truly predominant air-
borne transmission route, eventually sufficient numbers
of published studies will demonstrate its true nature
[13]. If there are ongoing contradictory findings in mul-
tiple studies (as with influenza virus), it may be more
likely that the various transmission routes (direct/indir-
ect contact, short-range droplet, long-, and even short-
range airborne droplet nuclei) may predominate in
different settings [16,20], making the airborne route for
that particular pathogen more of an opportunistic
pathway, rather than the norm [21]. Several examples
may make this clearer.
The selected pathogens and supporting literature
summarized below are for illustrative purposes only, to
demonstrate how specific studies have impacted the way
we consider such infectious agents as potentially airborne
and ‘aerosol-transmissible’. It is not intended to be a sys-
tematic review, but rather to show how our thinking may
change with additional studies on each pathogen, and how
the acceptance of “aerosol transmission”for different path-
ogens did not always followed a consistent approach.
Results and discussion
Chickenpox
Chickenpox is a febrile, vesicular rash illness caused by vari-
cella zoster virus (VZV), a lipid-enveloped, double-stranded
DNA virus, and a member of the Herpesviridae family.
For chickenpox, the evidence appears to be mainly
epidemiological and clinical, though this has appeared to
be sufficient to classify varicella zoster virus (VZV) as an
airborne agent. Studies on VZV have shown that the virus
is clearly able to travel long distances (i.e. up to tens of me-
ters away from the index case, to spread between isolation
rooms and other ward areas connected by corridors, or
within a household) to cause secondary infections and/or
settle elsewhere in the environment [22–24]. In addition,
Tang et al. [25] showed that airborne VZV could leak out
of isolation rooms transported by induced environmental
airflows to infect a susceptible HCW, most likely via the
direct inhalation route.
Measles
Measles (also known as rubeola) is a febrile, rash illness
caused by the measles virus, a lipid-enveloped, single-
stranded, negative-sense RNA virus, and a member of
the Paramyxoviridae family.
For measles several studies examined a more mechanistic
airflow dynamical explanation(i.e.baseduponthefunda-
mental physics and behaviour of airborne particles) for the
main transmission route involved in several measles out-
breaks [26], including that of Riley and colleagues who used
the concept of ‘quanta’of infection [27]. Later, two other
outbreaks in outpatient clinics included retrospective
airflow dynamics analysis, providing more evidence for the
transmissibility of measles via the airborne route [28,29].
Tuberculosis
Tuberculosis is a localized or systemic, but most often
respiratory bacterial illness caused by mycobacteria
belonging to the Mycobacterium tuberculosis complex.
For tuberculosis (TB), definitive experimental evidence
of airborne transmission being necessary and sufficient to
cause disease was provided in a series of guinea-pig exper-
iments [30,31], which has been repeated more recently in
a slightly different clinical context [32]. Numerous other
outbreak reports have confirmed the transmissibility of
TB via the airborne route [33–35], and interventions
specifically targeting the airborne transmission route have
proven effective in reducing TB transmission [36].
Smallpox
Smallpox is a now eradicated, febrile, vesicular rash and
disseminated illness, caused by a complex, double-
stranded DNA orthopoxvirus (Poxviridae family), which
can present clinically in two forms, as variola major or
variola minor.
For smallpox, a recent comprehensive, retrospective
analysis of the literature by Milton has suggested an im-
portant contribution of the airborne transmission route
for this infection [37]. Although various air-sampling
and animal transmission studies were also reviewed, Mil-
ton also emphasized clinical epidemiological studies
where non-airborne transmission routes alone could not
account for all the observed smallpox cases.
At least one well-documented hospital outbreak, involv-
ing 17 cases of smallpox, could only be explained by
assuming the aerosol spread of the virus from the index
case, over several floors. Retrospective smoke tracer ex-
periments further demonstrated that airborne virus could
easily spread to patients on different floors via open
windows and connecting corridors and stairwells in a
pattern roughly replicating the location of cases [38].
Emerging coronaviruses: Severe acute respiratory
syndrome (SARS), middle-east respiratory syndrome
(MERS)
Coronaviruses are lipid-enveloped, single-stranded positive
sense RNA viruses, belong to the genus Coronavirus and
include several relatively benign, seasonal, common cold vi-
ruses (229E, OC43, NL63, HKU-1). They also include two
new more virulent coronaviruses: severe acute respiratory
syndrome coronavirus (SARS-CoV), which emerged in the
human population in 2003; and Middle-East Respiratory
Syndrome coronavirus (MERS-CoV), which emerged in
humans during 2012.
For SARS-CoV, several thorough epidemiological studies
that include retrospective airflow tracer investigations are
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consistent with the hypothesis of an airborne transmission
route [39–41]. Air-sampling studies have also demonstrated
the presence of SARS-CoV nucleic acid (RNA) in air,
though they did not test viability using viral culture [42].
Although several studies compared and contrasted
SARS and MERS from clinical and epidemiological an-
gles [43–45], the predominant transmission mode was
not discussed in detail, if at all. Several other studies do
mention the potential for airborne transmission, when
comparing potential routes of infection, but mainly in
relation to super-spreading events or “aerosolizing pro-
cedures”such as broncho-alveolar lavage, and/or a po-
tential route to take into consideration for precautionary
infection control measures [46–48]. However, from the
various published studies, for both MERS and SARS, it
is arguable that a proportion of transmission occurs
through the airborne route, although this may vary in
different situations (e.g. depending on host, and environ-
mental factors). The contribution from asymptomatic
cases is also uncertain [49].
For both SARS and MERS, LRT samples offer the best
diagnostic yield, often in the absence of any detectable
virus in upper respiratory tract (URT) samples [50–52].
Furthermore, infected, symptomatic patients tend to
develop severe LRT infections rather than URT disease.
Both of these aspects indicate that this is an airborne
agent that has to penetrate directly into the LRT to pref-
erentially replicate there before causing disease.
For MERS-CoV specifically, a recent study demon-
strated the absence of expression of dipeptidyl peptidase
4 (DPP4), the identified receptor used by the virus, in
the cells of the human URT. The search for an alternate
receptor was negative [53]. Thus, the human URT would
seem little or non-permissive for MERS-CoV replication,
indicating that successful infection can only result from
the penetration into the LRT via direct inhalation of
appropriately sized ‘droplet nuclei’-like’particles. This
makes any MERS-CoV transmission leading to MERS
disease conditional on the presence of virus-containing
droplets small enough to be inhaled into the LRT where
the virus can replicate.
Influenza
Influenza is a seasonal, often febrile respiratory illness,
caused by several species of influenza viruses. These are
lipid-enveloped, single-stranded, negative-sense, segmented
RNA viruses belonging to the Orthomyxoviridae family.
Currently, influenza is the only common seasonal respira-
tory virus for which licensed antiviral drugs and vaccines
are available.
For human influenza viruses, the question of airborne
versus large droplet transmission is perhaps most con-
troversial [54–57]. In experimental inoculation experi-
ments on human volunteers, aerosolized influenza
viruses are infectious at a dose much lower than by nasal
instillation [58]. The likely answer is that both routes are
possible and that the importance and significance of
each route will vary in different situations [16,20,21].
For example, tighter control of the environment may
reduce or prevent airborne transmission by: 1) isolating
infectious patients in a single-bed, negative pressure iso-
lation room [25]; 2) controlling environmental relative
humidity to reduce airborne influenza survival [59]; 3)
reducing exposure from aerosols produced by patients
through coughing, sneezing or breathing with the use of
personal protective equipment (wearing a mask) on the
patient (to reduce source emission) and/or the health-
care worker (to reduce recipient exposure) [60]; 4) care-
fully controlling the use and exposure to any respiratory
assist devices (high-flow oxygen masks, nebulizers) by
only allowing their use in designated, containment areas
or rooms [61]. The airflows being expelled from the side
vents of oxygen masks and nebulisers will contain a mix-
ture of patient exhaled air (which could be carrying air-
borne pathogens) and incoming high flow oxygen or air
carrying nebulized drugs. These vented airflows could
then act as potential sources of airborne pathogens.
Numerous studies have shown the emission of influenza
RNA from the exhaled breath of naturally influenza-
infected human subjects [62–66] and have detected influ-
enza RNA in environmental air [67–69]. More recently,
some of these studies have shown the absence of [70], or
significantly reduced numbers of viable viruses in
air-samples with high influenza RNA levels (as tested by
PCR) [66,71,72]. The low number of infectious particles
detected is currently difficult to interpret as culture
methods are inherently less sensitive than molecular
methods such as PCR, and the actual operation of air-
sampling itself, through shear-stress related damage to the
virions, also causes a drop in infectivity in the collected
samples. This may lead to underestimates of the amount of
live virus in these environmental aerosols.
An additional variable to consider is that some animal
studies have reported that different strains of influenza
virus may vary widely in their capacity for aerosol trans-
mission [73].
In some earlier articles that discuss the predominant
mode of influenza virus transmission [74–78], these same
questions are addressed with mixed conclusions. Most of
the evidence described to support their views was more
clinical and epidemiological, and included some animal
and human volunteer studies, rather than physical and
mechanistic. Yet, this mixed picture of transmission in dif-
ferent circumstances is probably the most realistic.
It is noteworthy that several infections currently ac-
cepted as airborne-transmitted, such as measles,
chickenpox or TB present, in their classical form, an un-
mistakable and pathognomonic clinical picture. In
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contrast the clinical picture of influenza virus infection
has a large overlap with that of other respiratory viruses,
and mixed outbreaks have been documented [79]. Thus,
a prevalent misconception in the field has been to study
‘respiratory viruses’as a group. However, given that
these viruses belong to different genera and families,
have different chemical and physical properties and dif-
fering viral characteristics, it is unwise and inaccurate to
assume that any conclusions about one virus can be ap-
plied to another, e.g. in a Cochrane review of 59 pub-
lished studies on interventions to reduce the spread of
respiratory viruses, there were actually only two studies
specifically about influenza viruses [80]. As the authors
themselves pointed out, no conclusion specific to influ-
enza viruses was possible.
While many airborne infections are highly contagious,
this is not, strictly speaking, part of the definition. Even so,
the lower contagiousness of influenza compared to, say,
measles has been invoked as an argument against a signifi-
cant contribution of airborne transmission. Yet, it should
be noted that a feature of influenza virus infections is that
the incubation time (typically 1–2 days) is much shorter
than its duration of shedding. This allows for the possibility
that a susceptible person will be exposed during an out-
break to several different infectious cases belonging to
more than one generation in the outbreak. This multiple
exposure and telescoping of generations may result in an
underestimate of influenza virus transmissibility, as fewer
secondary cases will be assigned to a known index case,
when in fact the number of secondary cases per index
could be much higher. For example, it is known that in
some settings a single index case can infect a large number
of people, e.g. 38 in an outbreak on an Alaska Airlines
flight [11].
Ebola
Ebola is a viral hemorrhagic fever associated with a very
high mortality, caused by the Ebola viruses; these are envel-
oped single-strand, negative-sense RNA viruses comprising
five species within the family Filoviridae. Four Ebola species
have been implicated in human diseases; the most wide-
spread outbreak, also the most recent, was caused by Ebola
Zaire in West Africa in 2013–2016. The transmission of
Ebola viruses has been reviewed in depth by Osterholm
et al. (4). These authors noted the broad tissue tropism, as
well as the high viral load reached during illness and the
low infectious dose, from which it appears inescapable that
more than one mode of transmission is possible.
Regarding aerosol transmission, concerns are raised by
several documented instances of transmission of Ebola
Zaire in laboratory settings between animals without direct
contact [81,82] (also reviewed in [4]). Experimental infec-
tions of Rhesus monkeys by Ebola Zaire using aerosol in-
fection has been shown to be highly effective [83,84]and
this experimental procedure has in fact been used as infec-
tious challenge in Ebola vaccine studies [85,86]. Rhesus
monkeys infected by aerosol exposure reliably developed
disseminated, fatal infection essentially similar to that
caused by parenteral infection with the addition of involve-
ment of the respiratory tract. Autopsies showed patho-
logical findings in the respiratory tract and respiratory
lymphoid system in animals infected by the aerosol route
that are not found in animals infected parenterally [83,84].
Such respiratory pathological lesions have not been re-
ported in human autopsies of Ebola cases, but as noted
by Osterholm et al. [4], there have been few human aut-
opsies of Ebola cases, arguably too few to confidently
rule out any possibility of disease acquired by the aerosol
route. The precautionary principle would therefore dic-
tate that aerosol precautions be used for the care of in-
fected patients, and especially considering that infection
of the respiratory tract in such patients is not necessary
to create an aerosol hazard: Ebola viruses reach a very
high titer in blood or other bodily fluids during the ill-
ness [87,88] and aerosolization of blood or other fluids
would create a significant airborne transmission hazard.
Conclusions
In summary, despite the various mechanistic arguments
about which organisms can be potentially airborne and
therefore aerosol-transmissible, ultimately, the main decid-
ing factor appears to be how many studies using various
differing approaches: empirical (clinical, epidemiological),
and/or experimental (e.g. using animal models), and/or
mechanistic (using airflow tracers and air-sampling)
methods, reach the same consensus opinion. Over time,
the scientific community will eventually form an impression
of the predominant transmission route for that specific
agent, even if the conclusion is one of mixed transmission
routes, with different routes predominating depending on
the specific situations. This is the case for influenza viruses,
and is likely the most realistic.
Some bacterial and viral infections that have more
than one mode of transmission are also anisotropic, like
anthrax, plague, tularemia and smallpox: the severity of
the disease varies depending on the mode of transmis-
sion [37,89]. Older experimental infection experiments
on volunteers suggest that this is the case for influenza,
with transmission by aerosols being associated with a
more severe illness [14,90], and some more recent field
observations are consistent with this concept [57]. For
anisotropic agents, even if a mode of transmission (e.g.
aerosols) accounts for only a minority of cases, interrup-
tion of that route of transmission may be required if it
accounts for the most severe cases.
Abbreviations
LRT: lower respiratory tract; MERS-CoV: Middle East Respiratory Syndrome-
associated coronavirus; PCR: polymerase chain reaction; RNA: ribonucleic
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acid; SARS-CoV: severe acute respiratory syndrome-associated coronavirus;
TB: tuberculosis; URT: upper respiratory tract; VZV: varicella zoster virus
Acknowledgements
None.
Funding
None required.
Availability of data and materials
All studies cited/discussed are already published and in the public domain –
some require the relevant journal subscriptions for access.
Disclaimer
Please note that the views expressed here are solely those of the authors
and are not representative of the institutions to which they are affiliated.
Authors’contributions
JWT, RT, BJC developed the original concept and outline of the article; YL
contributed the figures and some additional related text; all authors critically
reviewed the final version of the manuscript. All authors read and approved
the final manuscript.
Ethics approval and consent to participate
Not required. No individual patient information is included. Only previously
published papers are discussed.
Consent for publication
Not applicable.
Competing interests
None of the authors have any competing interests to declare.
Publisher’sNote
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Author details
1
Department of Pathology and Laboratory Medicine, University of Calgary,
Calgary, AB, Canada.
2
Department of Mechanical Engineering, University of
Hong Kong, Pokfulam, Hong Kong, Special Administrative Region of China.
3
WHO Collaborating Centre for Infectious Disease Epidemiology and Control,
School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong,
Special Administrative Region of China.
4
Department of Infection, Immunity
and Inflammation, University of Leicester, Leicester, UK.
5
Clinical
Microbiology, University Hospitals of Leicester NHS Trust, Level 5
Sandringham Building, Leicester Royal Infirmary, Infirmary Square, Leicester
LE1 5WW, UK.
Received: 29 August 2017 Accepted: 10 January 2019
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