Abstract: Viral infections of the upper and lower respiratory tracts are among the most common illnesses in humans.Humans have witnessed severe viral pandemic like Spanish influenza, H1N1, SARS-CoV, MERS-CoV and most recent and most severe SARS-CoV-2. Understanding of the modes of respiratory viral diseases transmission is of extreme importance for policy making for prevention and treatment of diseases.Airborne transmission via aerosols allows some of these viruses to spread efficiently among humans, causing outbreaks that are hard to control.Published evidence shows that aerosol transmission of viruses likeinfluenza and corona virus can be an important mode of transmission, which has obvious implications for pandemic planning.We here summarise an overview of the available data from experimental and observational studies on the aerosol transmission of respiratory viruses between humans. This type of studies provides information about aerosol transmission based on which new treatment opportunities can be developed.
Acute respiratory infections, particularly viral respiratory infections are one of the main causes of morbidity and mortality globally and lead to the development of other diseases (Alonso et al.,2012).The novel coronavirus (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV),Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza A viruses are main pathogens that mainly target the human respiratory system.Diseases related with their infections vary from mild respiratory infection to acute pneumonia and even respiratory failure(Abdelrahman et al.,2020).
The influenza A viruses caused four pandemics. The most severe pandemic is known as “Spanish Flu” occurred in 1918 and was caused by an H1N1 influenza A virus (Jorden et al.,2020). Around 50 million people died during this pandemic. Around 1.1 million died worldwide in “Asian Flu” pandemic in 1957 caused by an H2N2 IAV influenza strain(Glezen 1996). In 1968, “Hong Kong flu,” occurred which was caused by an H3N2 IAV strain which cause around 1 million deaths worldwide (Viboud et al.,2005).The fourth pandemic was caused by the influenza A (H1N1) pdm09 virus, caused 151,700–575,400 deaths globally from 2009 to 2010 (Garten et al.,2009;Shieh et al.,2010). Later, the novel influenza A virus has continued to spread as a seasonal flu virus. From September 2019 to February 2020, this virus triggered at least 34 million flu illnesses and 20,000 deaths (Abdelrahman et al.,2020).
Three highly pathogenic and lethal coronavirus strain namelySARS-CoV, MERSCoV and SARS-CoV-2 has caused terrible impacts on humans.SARS-CoV, MERSCoV, and SARS-CoV-2 are prone to infect the lower respiratory tract which results in acute lung damageand acute respiratory distress syndrome (ARDS), septic shock and multi-organ failurewhich leads to high case fatality ratio (CFR) (Peiris et al.,2003). SARS-CoV was first appeared in Foshan, China in November 2002(Zhong et al.,2003) and later transported to Hong Kong in February 2003, then spreadworldwide(Hui and Zumla.,2019).
The epidemic was finally controlled in July 2003(WHO 2003). There were four cases of SARS re-emergence that occurred in Singapore, Taipei, Guangdong and Beijing afterwards (Cherry 2004). No case of SARS has been reported since May 2004(Zhu et al.,2020). Another deathful hCoV arisesafter a decade.MERS-CoV0 was first occurred in April 2012 in Jordan (Hijawi et al.,2012)and spread to countries of Middle East regions and worldwide(Memish et al.2020). The most current laboratory-confirmed case was reported in Riyadh on 28 March 2020 (WHO 2020).
SARS-CoV-2 was first occurred in Wuhan, China in December 2019 and it quickly spread across China and aggressively infecting people worldwide.It isrecognized as a pandemic on 11 March 2020 which makes SARS-CoV-2 the first hCoV to cause a pandemic.Globally, as of 1 March 2021, there have been 113,695,296 confirmed cases of COVID-19, including 2,526,007 deaths as reported to WHO(WHO 2020).
Respiratory viruses reproduce in the respiratory tract from where they are subsequently shed and transmitted via respiratory secretions.Respiratory viruses transmitthrough three different transmission ways: the long-range airborne transmission, the close contact transmission, and the fomite transmission(Ching et al.,2007; Siegel etal.,2007)Contact transmission refers to direct virus transfer from an infected individual to a vulnerable individual (e.g., via contaminated hands) andindirect virus transfer refers transmission of virus via intermediate objects (fomites)(Gralton et al.,2011; Tellier 2009).
Transmission of virus through the air can occur by means of droplets or aerosols. According to, The World Health Organization (WHO) and Centres for Disease Control and Prevention (CDC) transmission of diseases with particles more than 5µm is consider as droplets transmission and with particles sized5µm or less is consider as aerosol transmission (Siegel et al.,2007;WHO 2014). Both droplets and aerosols can be created during coughing, sneezing, talking or exhaling, but large droplets settle rapidly while small aerosols can remain in air and may transport over longer distances by airflow (Edwards et al.,2004; Fabian et al.,2011).
Ordinary breathing and speech both emit large quantities of aerosol(Papineni and Rosenthal., 1997; Stadnytskyi et al.,2020). aerosol produced by breathing and speech are typically about 1 µm in diameter. Most people are completely unaware that they exist. The particles are appropriately largeto carry viruses such as SARS CoV 2, and to be readily inhaled deep into the respiratory tract of a susceptible individual (Wang.,2020).
According to Experimental work byJohnson and Morawska et al. (Johnson and Morawska 2009), vocalizationproduces up to an order of magnitude more aerosol particles than breathing.According to research work of Asadi et al. (Asadi et al.,2009), the louder one speaks, the more aerosol particles are produced.
Asadi et al. further established that,certain people are “speech super emitters” who release an order of magnitude more aerosol particles than average, about 10 particles/s. A 10 min talk with an infected, asymptomatic super emitter talking in a regular volume thus would produce an unseen “cloud” of approximately 6000 aerosol particles that could potentially be inhaled by the vulnerable conversational partner or others in close proximity (Asadi et al.,2009).
Particles produced by breathing have a velocity of approximately 1 m/s, talking 5 m/s, coughing 10 m/s, and sneezing 20–50 m/s. (XieX et al.,2007) Speech is possibly of much greater worry than breathing for two reasons: the aerosol on usual are larger and could potentially carry a larger number of pathogensand alsomuch greater amounts of particles are released compared to breathing, so increasing the chances of infecting nearby vulnerableindividuals. (Asadi et al.,2019).
Unlike droplets, aerosols can pose an infection risk over a greater distance. Small aerosols are possibly inhaled deep into the lung and cause infection in the alveolar tissues of the lower respiratory tract, while large droplets are stuck in the upper airways (Nicas et al.,2005). Thus, infection via aerosols may lead to more severe disease (Knight 1973; Knight 1980).
The fate of droplets and aerosol largely depends on environmental factors such as humidity, temperature, turbulence, and thermal convection including meteorology, vehicle/human activity, and ventilation. (Morawska et al.,2006).
Droplets generated during coughing, sneezing or talking do not remain suspended in air and travel less than 1 m before settling on the mucosa of close contacts or environmental surfaces. Aerosols have a slow settling velocity;thus, they remain suspended in the air longer and can travel further (Tellier et al.,2019; Nicas et al.,2005; Judson et al.,2019).
The current guidance from numerous international and national bodies focuses on hand washing, maintaining social distancing, and droplet precautions. Most public health organizations, including the World Health Organization (WHO), do not recognize airborne transmission except for aerosol-generating procedures performed in healthcare settings. Hand washing and social distancing are appropriate, but in our view, insufficient to provide protection from virus-carrying respiratory microdroplets released into the air by infected people. This problem is especially acute in indoor or enclosed environments, particularly those that are crowded and have inadequate ventilation relative to the number of occupants and extended exposure periods. For example, airborne transmission appears to be the only plausible explanation for several superspreading events investigated which occurred under such conditions and others where recommended precautions related to direct droplet transmissions were followed (Morawska and Junji., 2020).
Hand washing and maintaining social distance are the main actionssuggested by the World Health Organization (WHO) to avoid contracting respiratory viral infections. Unfortunately, these actions do not stop infection by inhalation of small droplets respired by an infected person that can travel distance of meters or tens of meters in the air and carry their viral content. Science clarifies the mechanisms of such transport and there is indication that this is animportant route of infection in indoor environments. Despite this, no countries or authorities deliberate airborne spread of respiratory viral diseases in their regulations to prevent infections transmission indoors. It is therefore very important, that the national authorities recognize the reality that the virus spreads through air.
Various studies have been performed to found mode of transmission of various virus causing respiratory illness.Published evidence specifies that aerosol transmission of various respiratory virus can be an important mode of transmission, which has clearsuggestions for pandemic planning andspecific for recommendations about the use of N95 respirators and personal protective equipment as part of treatment.Influenza A virus
There is significant support in the scientific literature for a role of aerosol transmission to the spread of influenza A. Over the past few years manystudies have been published which support to the theory that aerosol transmission plays an important role in the spread of influenza (Tellier et al.,2006).Fabian and colleagues (Fabian et al.,2008) spotted influenza virus RNA in aerosol particles produced by normal breathing in patients with influenza and collected it with an oronasal facemask. Patients were selected on the basis of symptoms and a positive rapid detection test for influenza. Out of 12 patients, four had influenza virus RNA in exhaled breath measured by quantitative RT –PCR and one patient with influenza A exhaled 20 RNA copies/minute, the three others exhaled less than 3.2 RNA copies/minute. Assessment of the size of the particles showed that 87 per cent of the exhaled particles had a diameter of less than 1 µmand less than 0.1 per cent larger than 5 µm. Blachere and colleagues (Blachere et al.,2009) reported bioaerosol of influenza viruses in a hospital emergency department. Aerosol samples were collected over the passage of 4 – 5 husing aerosol sampling that allowed for size fractionation. Samples were analysed by quantitative RT –PCR method.influenza RNA was detected in 14 samples; the largest amounts of RNA recovered were in the fraction of particles greater than 4 µm. Airborne transmission can account for around half of all household influenza A virus transmission events (Cowling, et al.,2013).Theinfluenza A virus exhibits 20-fold higher infectivity through inhalation than intranasal inoculation (Teunis et al.,2010).
Studies have confirmed that influenza virus can persist infectious in small particle aerosols, and can transfer across rooms (Noti et al.,2012). Influenza viral RNA has been spotted in a hospital emergency section (Blachere et al.,2009) and aerosol transmission was implicated in a hospital in epidemic of seasonal influenza (Wong et al.,2010). These data validate the potential involvement of aerosols to influenza transmission. Ferret studies have provided indicationin supporting the aerosol transmission of influenza virus transmission (Tellier et al.,2009), and one study in the 1940s provided evidence supporting aerosol transmission (Andrewes and Glover.,1941).
Study conducted by Coleman and his colleague in public elementary school for presence of aerosol of influenza A virus(IAV) densities.Air samples were collected from multiple locations in the school, two days per week, throughout an eight-week during influenza season. Real-time RT-PCR targeting theinfluenza A virus M gene revealed measurable IAV on five occasions.The majority of IAVaerosol particles were ≤4 μm in diameter. This study represents the firstidentification and quantification of airborne influenza virus inschooland the results suggest that airborne IAV is circulate in schools during influenza season which may cause infection (Coleman and sigler.,2020).
According to Studies conducted in Hong Kong and Bangkok households,the aerosol transmission accounts for around half of all transmission of influenza A virus. This suggests that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households. Studies also find that infections via aerosol transmission may have a higher risk of febrile illness (Cowling et al.,2013).
Scientists team in Singapore conducted study to improve respiratory virus surveillance. Theyused a non-invasive bioaerosol sampling method to detect respiratory viruses in Singapore’s Mass Rapid Transit (MRT) network. Over a phase of 52 weeks, 89 aerosol samples were collected. Out of them, one (1%) were tested positive for influenza A virus using real-time RT-PCR.This studyindicates the possibility of bioaerosol in crowded public spaces (Coleman et al.,2018).
In study conducted by scientists in Hospital of Qinhuangdao During 2017–2018 Flu Season showed that the air samples collected from the children's wards, adult ward and fever clinic were detected with airborne influenza viruses.Remarkably, a new developed subtype of pH1N1 (an epidemic in 2018) was detected in the aerosol samples. This study showed that patients infected with influenza could release airborne particles comprising the virus into their environment. Healthcare workers and visitors in thoseplaces have frequent contactwith airborne influenza virus. So, scientist recommend some protective measures such as air disinfection and mask wearing to prevent and control the transmission of airborne influenza in hospital (Zhaoet al.,2019).
In the guinea pig model of influenza virus transmission, scientists showed that an uninfected, virus-immune guinea pig whose body is contaminated with influenza virus can spread the virus through the air to a vulnerable partner in a separate cage (Mubareka et al.,2009).Severe acute respiratory syndrome (SARS)
The epidemic of severe acute respiratory syndrome (SARS) had a noteworthy effect on worldwide in the early 2000s. Studies on the modes of transmission of SARS are limited however a number of outbreak studies have revealed the possible airborne route (Abdelrahman et al.,2020).
Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol droplets or direct personal contact s. This paper presents a detailed study of environmental evidence of possible airborne transmission in a hospital ward during the largest nosocomial SARS outbreak in Hong Kong in March 2003. Retrospective on-site inspections and measurements of the ventilation design and air distribution system were carried out on July 17, 2003. Limited on- site measurements of bio-aerosol dispersion were also carried out on July 22. Computational ﬂuid dynami cs simulations were performed to analyze the bio- aerosol dispersion in the hospital ward. We attempted to predict the air distri- bution during the time of measurement in July 2003 and the time of exposure in March 2003. The predicted bio-aerosol concentration distribution in the ward seemed to agree fairly well with the spatial infection pattern of SAR S cases. Possible improvement to air distribution in the hospital ward was also consid-ered During the Toronto outbreaks of SARS, Booth et al., investigated environmental contamination in SARS by using novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)–positive air samples were found from a room occupied by a patient with SARS which indicate the presence of the virus in the air of the room. Some PCR-positive swab samples were recovered from commonly touched surfaces in rooms occupied by patients with SARS These data offer the first experimental validation of viral aerosol generation by a patient with SARS which indicate the possibility of aerosol transmission, which highlights the need for adequate respiratory protection and strict surface hygiene practice (66).
Severe acute respiratory syndrome (SARS) is mainlyspread by bio-aerosol or direct personal contact. scientistsperformed a detailed study of environmental evidence of possible airborne transmission in a hospital during the largest nosocomial SARS outbreak in Hong Kong in 2003. Surveying on-site examinations and measurements of the ventilation design and air distribution system were carried out. Limited onsite measurements of bio-aerosol dispersion were also carried out. Computational fluid dynamics simulations were performed to analyse the bioaerosol dispersion in the hospital ward.The predicted bio-aerosol concentration distribution in the ward appeared to approve fairly well with the spatial contamination pattern of SARS cases (Li et al.,2004).
Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol droplets or direct personal contact s. This paper presents a detailed study of environmental evidence of possible airborne transmission in a hospital ward during the largest nosocomial SARS outbreak in Hong Kong in March 2003. Retrospective on-site inspections and measurements of the ventilation design and air distribution system were carried out on July 17, 2003. Limited on- site measurements of bio-aerosol dispersion were also carried out on July 22. Computational ﬂuid dynami cs simulations were performed to analyze the bio-aerosol dispersion in the hospital ward. We attempted to predict the air distri-bution during the time of measurement in July 2003 and the time of exposure in March 2003. The predicted bio-aerosol concentration distribution in the ward seemed to agree fairly well with the spatial infection pattern of SAR S cases. Possible improvement to air distribution in the hospital ward was also consid-ered In another scientific report by Ignatius et al., the temporal-spatial spread of severe acute respiratory syndrome (SARS) among patients in a hospital ward were studied. The concentration of virus-laden aerosols at different locations of the ward was assessed by using computational fluid dynamics modelling. The attack rates in the various subgroups graded by bed location were calculated.Results has showed thatthe overall attack rate of SARS was 41% (30 of 74 subjects). It was 65%, 52%, and 18% in the same bay, adjacent bay, and distant bays, correspondingly. Computation fluid dynamics modellingshowedthat thestandardized concentration of virus-laden aerosols was highest in the same bay and lowest in the distant bays. This study concluded that the temporal-spatial spread of SARS in the ward was consistent with airborne transmission and Infected health care workers possibly acted as secondary sources of infections (Ignatius et al.,2004).
To develop more precise and effective control strategiesXiao et al., studied a detailed mechanism-based investigation that discovered the role of fomite transmission. In this study they considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes. A multi-agent model was used to expect the infection risk distributions of the three hypothetical routes. Results revealed that under the presumed conditions, the SARS coronavirus was most likely to have spread via the combined long-range airborne and fomite routes (Xiao et al.,2017).
Olsen et al., studied air borne transmission of SARS in Aircraft. they findthat in one flight with a symptomatic person and 119 other persons, laboratory-confirmed SARS developed in 16 persons, 2 others were given diagnoses of possible SARS, and 4 were reported to have SARS but could not be questioned. Among the 22 persons with infection, the mean period from the flight to the onset of symptoms was four days (range, two to eight), and there were no recognized exposures to patients with SARS before or after the flight (Olsen et al.,2003).
Infection in travellers was connected to the physical closeness to the SARS patient, with infection reported in 8 of the 23 persons who were seated in the three rows in front of the patient, as compared with 10 of the 88 persons who were seated away. This concluded airborne transmission of SARS in aircraft (Olsen et al.,2003).Middle East Respiratory Syndrome coronavirus (MERS-CoV)
Study conducted by Bin et al., during MERS outbreak in Korea was to investigate the potential role of environmental contamination by MERS-CoV in healthcare surroundings and to outline the period of viable virus shedding from MERS patients.Teamexamined environmental contamination from 4 patients in MERS-CoV units of 2 hospitals.MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results showed that many environmental surfaces of MERS patient rooms which includesurfacesregularly touched by patients or healthcare workers were contaminated by MERS-CoV. MERS-CoV RNA was detected in samples from entrances, medical devices, and air-ventilating equipment. This study concluded thatmost of frequently touchable surfaces in MERS units were contaminated by MERS virus andthe virus could shed through respiratory secretion from clinically fully recovered patients (Bin et al.,2016).
Kim and colleagues studied the possible role of contaminated hospital air to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients in south Korea. The samples were tested by RT-PCRand immunofluorescence assay (IFA) using MERS-CoV Spike antibodyand electron microscopy (EM). Results showed the presence of MERS-CoV virus in 4 of 7 air samples from 2 patients’ rooms, 1 patient’s restroom, and 1 common corridor. IFA on the cultures of the air samples revealed the presence of MERS-CoV. EM images also revealed particles of MERS-CoV in viral cultures of the air. These data provide indication for extensive viable MERS-CoV contamination of the air in MERS outbreak units. So, these findingssuggest airborne transmission of MERS-CoV(Kim et al.,2017).
Alraddadi et al. investigated risk factors for MERS-CoV contamination in 20 healthcare workers in Saudi Arabia using serologic testing.They found that wearing a medical mask (as opposed to not wearing a medical mask) increased the risk for seropositivity while N95 respirator use amongst healthcare workers reduced the risk for seropositivity. This study suggested that aerosol transmission of MERS-CoV may be likely at close range, as seen with other respiratory viruses (e.g., influenza) (Alraddadi et al.,2016).
Xiao et al., examined the transmission routes of MERS-CoV during the first nosocomial epidemic in the Republic of Korea in May 2015 using a multi-agent modelling framework. They identified seven assumed transmission modes based on the three main transmission routes (longrange airborne, close contact, and fomite transmission). Theyrecommended that MERS-CoV probably spread via the long-range airborne route (Xiao et al.,2016).Severe acute respiratory syndrome corona virus 2(SARS -CoV-2)
There is increasing evidence that airborne transport in aerosol particles is important in the spread of SARS-CoV-2, in addition to infection through larger droplets from coughing or sneezing and surface deposits (fomites) (Wilson et al.,2020).
A current study at the University of Nebraska Medical Centre on SARS-CoV-2 aerosolization showed extensive presence of viral RNA in isolation rooms where patients with SARS-CoV-2 were getting care(Santarpia et al.,2020).
In one study conducted by Santarpia et al air and surface samples from 11 isolation rooms that were used to care for patients infected with SARS-CoV-2 were collected.In this study both high volume air samples and low volume personal air samples were included.air collectors were kept more than 6 feet from each of two patients andair samplers kept outside patient rooms in the hallways yielded samples positive for viral RNA when assessed using reverse-transcriptase PCR (RT-PCR).Personal collectors worn by technicians also were positive even though patients were not coughing whiletechnicians were present. The highest airborne RNA concentrations were documented while a patient was getting oxygen through a nasal cannula.This research indicates that viral particles can be spread via bioaerosols (Santarpia et al.,2020).
Liu et al. collected 35 aerosol samples in 2 hospitals and public areas in Wuhan. The highest concentration of the virus was found in toilet facilities from samples collected in patient care areas. The highest concentrations were identified in personal protective equipment (PPE) removal rooms in medical staff areas.Scientists conclude that a direct source of SARS-CoV-2 may be a virus-laden aerosol resuspended by the removing of PPE, the cleaning of floors and the movement of staff (Liu et al.,2020).
Scientists analysed an outbreak connecting three non-associated families in Restaurant X in Guangzhou, China, and evaluated the possibility of aerosol transmission of SARS-CoV-2 and describe the associated environmental conditions. They collected epidemiological data andgot a video record and a patron seating-arrangement from the restaurant, and measured the spreading of a warm tracer gas as a substitute for exhaled droplets from the suspected SARS-CoV-2 patient (Lu et al.,2020).
Computer simulations were executed to simulate the spread of fine exhaled droplets. Theylinked the in-room location of next infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured by means of the tracer decay method. Results showed that Three families (A, B, C), 10 members of which were later found to have been infected with SARS-CoV-2 at this time, ate lunch at Restaurant X on Chinese New Year's Eve (January 24, 2020) at three neighbouring tables.
Subsequently, three members of family B and two members of family C became sick with SARS-CoV-2, whereas none of the waiters or 68 patrons at the remaining 15 tables became infected. During this time, the ventilation rate was 0.75-1.04 L/s per person. Results showed that the contamination distribution is consistent with a spread pattern representative of exhaled virus-laden aerosols. This concluded thataerosol transmission of SARS-CoV-2 due to poor ventilation may explain the community spread of COVID-19(Lu et al.,2020).MVS Pharma is working on aerosol transmission of Viral diseases and this article is written by Dr Disha Trivedi who is expert in the field of biotechnology and has published several research and review articles in international journal.