Ten scientific reasons in support of airborne transmission of SARS-CoV-2
Authors: Trisha Greenhalgh, Jose L Jimenez, Kimberly A Prather, Zeynep Tufekci, David Fisman, Robert Schooley
Journal: The Lancet (2021)

Heneghan and colleagues' systematic review, funded by WHO, published in March, 2021, as a preprint, states: "The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission".1Heneghan C Spencer E Brassey J et al.SARS-CoV-2 and the role of airborne transmission: a systematic review.F1000Research. 2021; (published online March 24.) (preprint).https://doi.org/10.12688/f1000research.52091.1Crossref Scopus (23) Google Scholar This conclusion, and the wide circulation of the review's findings, is concerning because of the public health implications. If an infectious virus spreads predominantly through large respiratory droplets that fall quickly, the key control measures are reducing direct contact, cleaning surfaces, physical barriers, physical distancing, use of masks within droplet distance, respiratory hygiene, and wearing high-grade protection only for so-called aerosol-generating health-care procedures. Such policies need not distinguish between indoors and outdoors, since a gravity-driven mechanism for transmission would be similar for both settings. But if an infectious virus is mainly airborne, an individual could potentially be infected when they inhale aerosols produced when an infected person exhales, speaks, shouts, sings, sneezes, or coughs. Reducing airborne transmission of virus requires measures to avoid inhalation of infectious aerosols, including ventilation, air filtration, reducing crowding and time spent indoors, use of masks whenever indoors, attention to mask quality and fit, and higher-grade protection for health-care staff and front-line workers.2Prather KA Wang CC Schooley RT Reducing transmission of SARS-CoV-2.Science. 2020; 6498: 1422-1424Crossref Scopus (566) Google Scholar Airborne transmission of respiratory viruses is difficult to demonstrate directly.3Pan M Lednicky JA Wu CY Collection, particle sizing and detection of airborne viruses.J Appl Microbiol. 2019; 127: 1596-1611Crossref PubMed Scopus (152) Google Scholar Mixed findings from studies that seek to detect viable pathogen in air are therefore insufficient grounds for concluding that a pathogen is not airborne if the totality of scientific evidence indicates otherwise. Decades of painstaking research, which did not include capturing live pathogens in the air, showed that diseases once considered to be spread by droplets are airborne.4Gelfand HM Posch J The recent outbreak of smallpox in Meschede, west Germany.Am J Epidemiol. 1971; 93: 234-237Crossref PubMed Scopus (37) Google Scholar Ten streams of evidence collectively support the hypothesis that SARS-CoV-2 is transmitted primarily by the airborne route.5Morawska L Milton DK It is time to address airborne transmission of coronavirus disease 2019 (COVID-19).Clinical Infect Dis. 2020; 71: 2311-2313PubMed Google Scholar First, superspreading events account for substantial SARS-CoV-2 transmission; indeed, such events may be the pandemic's primary drivers.6Lewis D Superspreading drives the COVID pandemic—and could help to tame it.Nature. 2021; 590: 544-546Crossref PubMed Scopus (86) Google Scholar Detailed analyses of human behaviours and interactions, room sizes, ventilation, and other variables in choir concerts, cruise ships, slaughterhouses, care homes, and correctional facilities, among other settings, have shown patterns—eg, long-range transmission and overdispersion of the basic reproduction number (R0), discussed below—consistent with airborne spread of SARS-CoV-2 that cannot be adequately explained by droplets or fomites.6Lewis D Superspreading drives the COVID pandemic—and could help to tame it.Nature. 2021; 590: 544-546Crossref PubMed Scopus (86) Google Scholar The high incidence of such events strongly suggests the dominance of aerosol transmission. Second, long-range transmission of SARS-CoV-2 between people in adjacent rooms but never in each other's presence has been documented in quarantine hotels.7Eichler N Thornley C Swadi T et al.Transmission of severe acute respiratory syndrome coronavirus 2 during border quarantine and air travel, New Zealand (Aotearoa).Emerging Infect Dis. 2021; (published online March 18.)https://doi.org/10.3201/eid2705.210514Crossref PubMed Scopus (58) Google Scholar Historically, it was possible to prove long-range transmission only in the complete absence of community transmission.4Gelfand HM Posch J The recent outbreak of smallpox in Meschede, west Germany.Am J Epidemiol. 1971; 93: 234-237Crossref PubMed Scopus (37) Google Scholar Third, asymptomatic or presymptomatic transmission of SARS-CoV-2 from people who are not coughing or sneezing is likely to account for at least a third, and perhaps up to 59%, of all transmission globally and is a key way SARS-CoV-2 has spread around the world,8Johansson MA Quandelacy TM Kada S et al.SARS-CoV-2 transmission from people without COVID-19 symptoms.JAMA Netw Open. 2021; 4e2035057Crossref PubMed Scopus (637) Google Scholar supportive of a predominantly airborne mode of transmission. Direct measurements show that speaking produces thousands of aerosol particles and few large droplets,9Chen W Zhang N Wei J Yen H-L Li Y Short-range airborne route dominates exposure of respiratory infection during close contact.Building Environ. 2020; 176106859Crossref Scopus (257) Google Scholar which supports the airborne route. Fourth, transmission of SARS-CoV-2 is higher indoors than outdoors10Bulfone TC Malekinejad M Rutherford GW Razani N Outdoor transmission of SARS-CoV-2 and other respiratory viruses: a systematic review.J Infect Dis. 2021; 223: 550-561Crossref PubMed Scopus (217) Google Scholar and is substantially reduced by indoor ventilation.5Morawska L Milton DK It is time to address airborne transmission of coronavirus disease 2019 (COVID-19).Clinical Infect Dis. 2020; 71: 2311-2313PubMed Google Scholar Both observations support a predominantly airborne route of transmission. Fifth, nosocomial infections have been documented in health-care organisations, where there have been strict contact-and-droplet precautions and use of personal protective equipment (PPE) designed to protect against droplet but not aerosol exposure.11Klompas M Baker MA Rhee C et al.A SARS-CoV-2 cluster in an acute care hospital.Ann Intern Med. 2021; (published online Feb 9.)https://doi.org/10.7326/M20-567Crossref PubMed Scopus (102) Google Scholar Sixth, viable SARS-CoV-2 has been detected in the air. In laboratory experiments, SARS-CoV-2 stayed infectious in the air for up to 3 h with a half-life of 1·1 h.12Van Doremalen N Bushmaker T Morris DH et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.New Engl J Med. 2020; 382: 1564-1567Crossref PubMed Scopus (6695) Google Scholar Viable SARS-CoV-2 was identified in air samples from rooms occupied by COVID-19 patients in the absence of aerosol-generating health-care procedures13Lednicky JA Lauzard M Fan ZH et al.Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients.Int J Infect Dis. 2020; 100: 476-482Summary Full Text Full Text PDF PubMed Scopus (433) Google Scholar and in air samples from an infected person's car.14Lednicky JA Lauzardo M Alam MM et al.Isolation of SARS-CoV-2 from the air in a car driven by a COVID patient with mild illness.medRxiv. 2021; (published online Jan 15.) (preprint).https://doi.org/10.1101/2021.01.12.21249603PubMed Google Scholar Although other studies have failed to capture viable SARS-CoV-2 in air samples, this is to be expected. Sampling of airborne virus is technically challenging for several reasons, including limited effectiveness of some sampling methods for collecting fine particles, viral dehydration during collection, viral damage due to impact forces (leading to loss of viability), reaerosolisation of virus during collection, and viral retention in the sampling equipment.3Pan M Lednicky JA Wu CY Collection, particle sizing and detection of airborne viruses.J Appl Microbiol. 2019; 127: 1596-1611Crossref PubMed Scopus (152) Google Scholar Measles and tuberculosis, two primarily airborne diseases, have never been cultivated from room air.15Fennelly KP Particle sizes of infectious aerosols: implications for infection control.Lancet Respir Med. 2020; 8: 914-924Summary Full Text Full Text PDF PubMed Scopus (379) Google Scholar Seventh, SARS-CoV-2 has been identified in air filters and building ducts in hospitals with COVID-19 patients; such locations could be reached only by aerosols.16Nissen K Krambrich J Akaberi D et al.Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards.Sci Rep. 2020; 10: 1-9Crossref PubMed Scopus (126) Google Scholar Eighth, studies involving infected caged animals that were connected to separately caged uninfected animals via an air duct have shown transmission of SARS-CoV-2 that can be adequately explained only by aerosols.17Kutter JS de Meulder D Bestebroer TM et al.SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance.Nat Commun. 2021; 12: 1-8Crossref PubMed Scopus (104) Google Scholar Ninth, no study to our knowledge has provided strong or consistent evidence to refute the hypothesis of airborne SARS-CoV-2 transmission. Some people have avoided SARS-CoV-2 infection when they have shared air with infected people, but this situation could be explained by a combination of factors, including variation in the amount of viral shedding between infectious individuals by several orders of magnitude and different environmental (especially ventilation) conditions.18Schijven J Vermeulen LC Swart A Meijer A Duizer E de Roda Husman AM Quantitative microbial risk assessment for airborne transmission of SARS-CoV-2 via breathing, speaking, singing, coughing, and sneezing.Environ Health Perspect. 2021; 12947002Google Scholar Individual and environmental variation means that a minority of primary cases (notably, individuals shedding high levels of virus in indoor, crowded settings with poor ventilation) account for a majority of secondary infections, which is supported by high-quality contact tracing data from several countries.19Sun K Wang W Gao L et al.Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2.Science. 2021; 371eabe2424Crossref Scopus (232) Google Scholar, 20Laxminarayan R Wahl B Dudala SR et al.Epidemiology and transmission dynamics of COVID-19 in two Indian states.Science. 2020; 370: 691-697Crossref PubMed Scopus (289) Google Scholar Wide variation in respiratory viral load of SARS-CoV-2 counters arguments that SARS-CoV-2 cannot be airborne because the virus has a lower R0 (estimated at around 2·5)21Petersen E Koopmans M Go U et al.Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics.Lancet Infect Dis. 2020; 20: e238-e244Summary Full Text Full Text PDF PubMed Scopus (844) Google Scholar than measles (estimated at around 15),22Guerra FM Bolotin S Lim G et al.The basic reproduction number (R0) of measles: a systematic review.Lancet Infect Dis. 2017; 17: e420-e428Summary Full Text Full Text PDF PubMed Scopus (332) Google Scholar especially since R0, which is an average, does not account for the fact that only a minority of infectious individuals shed high amounts of virus. Overdispersion of R0 is well documented in COVID-19.23Endo A Abbott S Kucharski AJ Funk S Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.Wellcome Open Res. 2020; 5: 67Crossref PubMed Google Scholar Tenth, there is limited evidence to support other dominant routes of transmission—ie, respiratory droplet or fomite.9Chen W Zhang N Wei J Yen H-L Li Y Short-range airborne route dominates exposure of respiratory infection during close contact.Building Environ. 2020; 176106859Crossref Scopus (257) Google Scholar, 24Goldman E Exaggerated risk of transmission of COVID-19 by fomites.Lancet Infect Dis. 2020; 20: 892-893Summary Full Text Full Text PDF PubMed Scopus (271) Google Scholar Ease of infection between people in close proximity to each other has been cited as proof of respiratory droplet transmission of SARS-CoV-2. However, close-proximity transmission in most cases along with distant infection for a few when sharing air is more likely to be explained by dilution of exhaled aerosols with distance from an infected person.9Chen W Zhang N Wei J Yen H-L Li Y Short-range airborne route dominates exposure of respiratory infection during close contact.Building Environ. 2020; 176106859Crossref Scopus (257) Google Scholar The flawed assumption that transmission through close proximity implies large respiratory droplets or fomites was historically used for decades to deny the airborne transmission of tuberculosis and measles.15Fennelly KP Particle sizes of infectious aerosols: implications for infection control.Lancet Respir Med. 2020; 8: 914-924Summary Full Text Full Text PDF PubMed Scopus (379) Google Scholar, 25Tang JW Bahnfleth WP Bluyssen PM et al.Dismantling myths on the airborne transmission of severe acute respiratory syndrome coronavirus (SARS-CoV-2).J Hosp Infect. 2021; 110: 89-96Summary Full Text Full Text PDF PubMed Scopus (228) Google Scholar This became medical dogma, ignoring direct measurements of aerosols and droplets which reveal flaws such as the overwhelming number of aerosols produced in respiratory activities and the arbitrary boundary in particle size of 5 μm between aerosols and droplets, instead of the correct boundary of 100 μm.15Fennelly KP Particle sizes of infectious aerosols: implications for infection control.Lancet Respir Med. 2020; 8: 914-924Summary Full Text Full Text PDF PubMed Scopus (379) Google Scholar, 25Tang JW Bahnfleth WP Bluyssen PM et al.Dismantling myths on the airborne transmission of severe acute respiratory syndrome coronavirus (SARS-CoV-2).J Hosp Infect. 2021; 110: 89-96Summary Full Text Full Text PDF PubMed Scopus (228) Google Scholar It is sometimes argued that since respiratory droplets are larger than aerosols, they must contain more viruses. However, in diseases where pathogen concentrations have been quantified by particle size, smaller aerosols showed higher pathogen concentrations than droplets when both were measured.15Fennelly KP Particle sizes of infectious aerosols: implications for infection control.Lancet Respir Med. 2020; 8: 914-924Summary Full Text Full Text PDF PubMed Scopus (379) Google Scholar In conclusion, we propose that it is a scientific error to use lack of direct evidence of SARS-CoV-2 in some air samples to cast doubt on airborne transmission while overlooking the quality and strength of the overall evidence base. There is consistent, strong evidence that SARS-CoV-2 spreads by airborne transmission. Although other routes can contribute, we believe that the airborne route is likely to be dominant. The public health community should act accordingly and without further delay. This online publication has been corrected. The corrected version first appeared at thelancet.com on May 13, 2021 This online publication has been corrected. The corrected version first appeared at thelancet.com on May 13, 2021 TG's research is funded by the National Institute for Health Research (BRC-1215-20008), Economic and Social Research Council (ES/V010069/1), and Wellcome (WT104830MA). JLJ is supported by the US National Science Foundation (AGS-1822664). KAP is supported by the US National Science Foundation Center for Aerosol Impacts on the Chemistry of the Environment (CHE-1801971). DF is funded by the Canadian Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360), received consulting fees as a legal expert for Elementary Teachers Federation of Ontario in August and September, 2020, related to COVID-19 transmission in schools, including the importance of ventilation and masks for kids as source control, and currently serves as a legal expert for the Ontario Nurses Association on their challenge to Ontario Directive 5, which restricts access to N95 masks for healthcare workers except during performance of aerosol generating medical procedures. RS is supported by the National Institute of Allergy and Infectious Diseases (AI131424). We declare no other competing interests. Department of ErrorGreenhalgh T, Jimenez JL, Prather KA, Tufekci Z, Fisman D, Schooley R. Ten scientific reasons in support of airborne transmission of SARS-CoV-2. Lancet 2021; 397: 1603–05—In this Comment, the conflict of interest statement for David Fisman has been corrected according to what was declared on his ICMJE form to read: "DF is funded by the Canadian Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360), received consulting fees as a legal expert for Elementary Teachers Federation of Ontario in August and September, 2020, related to COVID-19 transmission in schools, including the importance of ventilation and masks for kids as source control, and currently serves as a legal expert for the Ontario Nurses Association on their challenge to Ontario Directive 5, which restricts access to N95 masks for health-care workers except during performance of aerosol generating medical procedures." This correction has been made to the online version as of May 13, 2021. Full-Text PDF Transmission of SARS-CoV-2: still up in the airTrisha Greenhalgh and colleagues claim that the dominant mode of SARS-CoV-2 transmission is likely to be airborne.1 However, many of the reasons that are cited as support for airborne transmission do not hold up to scrutiny. We acknowledge that transmission occurs along a spectrum and airborne spread is possible, particularly in crowded and poorly ventilated settings, but the epidemiology and scientific literature do not support airborne spread as the predominant mode of transmission. Full-Text PDF Transmission of SARS-CoV-2: still up in the air – Authors' replyWe welcome the opportunity to clarify the misconceptions that were raised by Alison Lopez and Jocelyn Srigley, which reflect a widely held but fundamentally flawed paradigmatic view among infection control clinicians. Full-Text PDF