In patient’s environment, there was an outlier, with 1 sample finding 94 000 SARS-CoV-2 RNA copies/m3 in 1 non–intensive care unit room.30
TCID50 indicates median tissue culture infectious dose.
eAppendix. Supplementary Methods
eTable. Evaluation of the Quality of Included Studies
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Birgand G, Peiffer-Smadja N, Fournier S, Kerneis S, Lescure F, Lucet J. Assessment of Air Contamination by SARS-CoV-2 in Hospital Settings. JAMA Netw Open. 2020;3(12):e2033232. doi:10.1001/jamanetworkopen.2020.33232
What is the level of air contamination from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different hospital areas, and what factors are associated with contamination?
In this systematic review of 24 studies, 17% of air sampled from close patient environments was positive for SARS-CoV-2 RNA, with viability of the virus found in 9% of cultures.
In this study, air both close to and distant from patients with coronavirus disease 2019 was frequently contaminated with SARS-CoV-2 RNA; however, few of these samples contained viable viruses.
Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
To review current evidence on air contamination with SARS-CoV-2 in hospital settings and the factors associated with contamination, including viral load and particle size.
The MEDLINE, Embase, and Web of Science databases were systematically queried for original English-language articles detailing SARS-CoV-2 air contamination in hospital settings between January 1 and October 27, 2020. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The positivity rate of SARS-CoV-2 viral RNA and culture were described and compared according to the setting, clinical context, air ventilation system, and distance from patients. The SARS-CoV-2 RNA concentrations in copies per meter cubed of air were pooled, and their distribution was described by hospital areas. Particle sizes and SARS-CoV-2 RNA concentrations in copies or median tissue culture infectious dose (TCID50) per meter cubed were analyzed after categorization as less than 1 μm, from 1 to 4 μm, and greater than 4 μm.
Among 2284 records identified, 24 cross-sectional observational studies were included in the review. Overall, 82 of 471 air samples (17.4%) from close patient environments were positive for SARS-CoV-2 RNA, with a significantly higher positivity rate in intensive care unit settings (intensive care unit, 27 of 107 [25.2%] vs non–intensive care unit, 39 of 364 [10.7%]; P < .001). There was no difference according to the distance from patients (≤1 m, 3 of 118 [2.5%] vs >1-5 m, 13 of 236 [5.5%]; P = .22). The positivity rate was 5 of 21 air samples (23.8%) in toilets, 20 of 242 (8.3%) in clinical areas, 15 of 122 (12.3%) in staff areas, and 14 of 42 (33.3%) in public areas. A total of 81 viral cultures were performed across 5 studies, and 7 (8.6%) from 2 studies were positive, all from close patient environments. The median (interquartile range) SARS-CoV-2 RNA concentrations varied from 1.0 × 103 copies/m3 (0.4 × 103 to 3.1 × 103 copies/m3) in clinical areas to 9.7 × 103 copies/m3 (5.1 × 103 to 14.3 × 103 copies/m3) in the air of toilets or bathrooms. Protective equipment removal and patient rooms had high concentrations per titer of SARS-CoV-2 (varying from 0.9 × 103 to 40 × 103 copies/m3 and 3.8 × 103 to 7.2 × 103 TCID50/m3), with aerosol size distributions that showed peaks in the region of particle size less than 1 μm; staff offices had peaks in the region of particle size greater than 4 μm.
Conclusions and Relevance
In this systematic review, the air close to and distant from patients with coronavirus disease 2019 was frequently contaminated with SARS-CoV-2 RNA; however, few of these samples contained viable viruses. High viral loads found in toilets and bathrooms, staff areas, and public hallways suggest that these areas should be carefully considered.
The transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain controversial.1 At the emerging stage of the pandemic, many countries implemented high-level precautions, including airborne and contact precautions, to prevent the spread from patients to health care professionals (HCPs).2 An emerging understanding of SARS-CoV-2 epidemiology, which is primarily transmitted from person to person through droplets, led to recommendations for droplet precautions to care for patients hospitalized with coronavirus disease 2019 (COVID-19).3 However, separating transmission dynamics into the dichotomy of droplet vs airborne transmission is probably simplistic. In some circumstances, aerosol particles (<5 μm in diameter) may be produced by individuals with infection and travel more than the 1.50 m commonly used to define transmission routes and contaminate surfaces further away.4
Environmental airflow may ease the spread of large particles.5 The switch from airborne to droplet precautions, combined with a global shortage of face masks and respirators, fed the controversy regarding respiratory protections to prevent transmission of SARS-CoV-2.6,7 This generated a mistrust in personal protective equipment (PPE), particularly regarding surgical masks and their ability to protect HCPs from SARS-CoV-2 transmission. As the World Health Organization recently acknowledged, airborne transmission could occur in crowded and closed environments in the community. This raises the question of whether similar transmission could occur in the hospital.1 Viral contamination of the air surrounding patients with COVID-19 and HCPs in hospitals may have serious implications for outbreak control strategies. We reviewed the current evidence on air contamination with SARS-CoV-2 in hospital settings, the viral load, and associated factors to better assess the risk of cross-transmission of COVID-19 among HCPs and patients.
We performed a systematic search of MEDLINE via PubMed, Embase, and Web of Science on October 27, 2020, with terms covering COVID-19 and air contamination in hospital settings in articles published between January 1 and October 27, 2020 (eAppendix in the Supplement). Because of potential delays in indexing of databases, we also searched selected infectious disease journals (eAppendix in the Supplement). We also searched some preprint servers, including BioRxiv and MedRxiv as well as the reference lists of identified articles to find reports of additional studies. We conducted this scoping systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews (eTable in the Supplement).
We included all literature related to COVID-19 published in English between January 1, 2020, and October 27, 2020, without restrictions, including original articles, research letters, and comments. We excluded experimental methods and studies performed in dental and primary care settings.
Two reviewers (G.B. and N.P.S.) screened all titles, abstracts, and full-text articles independently and resolved disagreements by consensus or consultation with a third reviewer (J.C.L.). The following information was then extracted: (1) setting, (2) clinical context, (3) ventilation system, (4) number of air samples performed, (5) sampling method, (6) location of sampler and distance from patients, (7) duration and air volume sampled, (8) method of SARS-CoV-2 search, (9) positivity rate, (10) viral load (SARS-CoV-2 RNA copies per m3), and (11) viral culture results.
We conducted a descriptive analysis of the characteristics of the included literature. We described the setting, patient clinical contexts, ventilation, air sampling and SARS-CoV-2 search methods, and the qualitative and quantitative results according to settings and the hospital area. We categorized the location of air sampling in 5 classes of hospital areas: close patient environments (ie, patient rooms or bays), toilet or bathroom, clinical areas (ie, workstations, anterooms or buffer rooms, corridors, and other spaces in the clinical unit), staff areas (ie, changing rooms, staff rooms including office, meeting rooms, dining rooms, and other staff areas), public areas (hallways and other indoor and outdoor public areas). When possible, we also classified the setting as intensive care unit (ICU) vs non-ICU; the clinical context as severe or critical vs mild, moderate, or asymptomatic; the ventilation system as negative pressure vs natural or mechanical; and the distance from patients as 1 m or less vs greater than 1 to 5 m. The positivity rate of viral RNA and the viral culture were pooled, described, and compared according to categories using a χ2 test. The results of SARS-CoV-2 RNA concentrations in copies per meter cubed of air were pooled, and their distribution was described by hospital areas. The Kruskall-Wallis test was used to compare the nonnormally distributed RNA concentrations across hospital areas. A 2-tailed P < .05 was considered statistically significant. Studies presenting the combined results of particle sizes and SARS-CoV-2 RNA concentrations in copies or median tissue culture infectious dose (TCID50) per meter cubed were analyzed after categorization of sizes as less than 1 μm, 1 to 4 μm, and greater than 4 μm, the thresholds available across the 3 studies.
We identified 2284 records, 671 (29.4%) of which were excluded as duplicates. Title and abstract screening were conducted for the remaining 1613 articles, 1458 (90.4%) of which were excluded because they were unrelated to air contamination by SARS-CoV-2 in hospital settings. We retrieved the full text of the 155 remaining articles. After further screening and supplementary searching of articles published or posted between January 1 and October 27, 2020, we identified an additional article, and a total of 24 articles were included in the review (Figure 1).3,8-30
Of the 24 included studies, all were cross-sectional observational studies. Ten studies (41.7%) were from China,9-11,15,18-20,22,25,29 and the remaining were from the United States (4 [16.7%]),12,13,26,30 Hong Kong (2 [8.3%]),14,21 Korea (2 [8.3%]),24,27 Singapore (2 [8.3%]),3,16 Iran (2 [8.3%]),8,28 the United Kingdom (1 [4.2%]),19 and Italy (1 [4.2%]).23 Of all included articles and studies, 20 (83.3%)3,8-11,14-17,20-30 were published in peer-reviewed journals, and 4 (16.7%)12,13,17,18 were posted on preprint servers.
A total of 23 studies (95.8%)3,8-19,21-30 sampled the air in the close patient environments, 12 (50.0%)3,9-12,17-20,23,24,28 in clinical areas away from patients, 8 (33.3%)9-13,19,23,29 in staff areas, 6 (25.0%)3,9,17-19,22 in toilets and/or bathrooms, and 6 (33.3%)9,10,12,17,20,28 in public areas (Table 1). The clinical context of patients hospitalized in the targeted areas was detailed in 18 studies, of which 10 (50.0%)8-11,22,23,25,27-29 were performed in units hospitalizing patients with severe or critical illness, 11 (61.1%)3,11,12,14-16,24-26,28,30 with patients with mild, moderate, or asymptomatic disease, and 4 studies (22.2%)11,14,25,28 with both categories.
A median of 24 air samples were collected per study, varying from 2 to 160 samples. In close patient environments, a median of 10 air samples (range, 1-160) were performed, 2.5 (range, 1-7) in toilets and/or bathrooms, 11 (range, 1-69) in clinical areas, 9 (range, 1-45) in staff areas, and 10 (1-12) in public areas. Overall, 19 studies (79.2%)3,8-17,19,22,23,25,26,28,30 sampled the air from non-ICU patient rooms, and 12 (50.0%)8-11,18,19,22,23,25,27-29 in ICU rooms. Among the 19 studies3,8-12,14,15,18,19,21,23-30 with the available information, 360 samples were taken in patient rooms with negative pressure and 66 with natural or mechanical ventilation. When pooling the 19 studies3,8,10-12,14-16,18,19,22,24-30 detailing the distance from patient, a total of 118 samples were performed 1 m or less from patients and 236 from greater than 1 to 5 m.
All included studies used reverse transcription–polymerase chain reaction (RT-PCR) to identify SARS-CoV-2 RNA, with a quantification of RNA copies per meters cubed or per liter in 8 studies (33.3%). One study9 used a droplet digital RT-PCR method. The viral culture was planned in the methods of 6 studies (20.8%)12,13,17,26,27,30 but performed in 5 (12.5%) of them.12,13,17,26,30 The remaining did not perform viral culture due to negative RT-PCR results. Three studies (12.5%)9,13,16 assessed the particle size in parallel to RNA concentration or viral titer.
A total of 893 air samples were performed across the 24 studies reviewed, including 471 (52.7%) in close patient environments, 237 (26.5%) in clinical areas, 122 (13.7%) in staff areas, 42 (4.7%) in public areas, and 21 (2.4%) in toilets and/or bathrooms (Table 2). Overall, 82 of 471 air samples (17.4%) from close patient environments were positive for SARS-CoV-2 RNA. Among the 107 samples performed in ICU rooms, 27 (25.2%) were positive vs 39 of 364 (10.7%) in non-ICU rooms (P < .001). The air RNA positivity rate was 47 of 360 (13.1%) in rooms with negative pressure and 6 of 66 (9.1%) in rooms with natural or mechanical ventilation. In toilets and/or bathrooms, 5 of 21 samples (23.8%) samples were positive. In clinical areas, the overall positivity rate was 8.4% (20 of 237), varying from 0 of 64 in anterooms or buffer rooms to 6 of 22 (27.2%) at workstations (P < .001). In staff areas, 15 of 122 samples (12.3%) were positive, with 5 of 26 (19.2%) in staff meeting rooms vs 2 of 51 (3.9%) in changing rooms and 8 of 45 (17.8%) in other types of staff rooms (P = .06). Overall, 14 of 42 samples (33.3%) in public areas were positive, with 9 of 16 (56.3%) in hallways, 2 of 18 (11.1%) in other indoor areas, and 3 of 8 (37.5%) in outdoor public areas (P = .01). A total of 81 viral cultures were performed across 3 studies (47 samples [58.0%] from close patient environment, 2 [2.5%] in toilets/bathroom, 13 [16.0%] in clinical areas, 4 [4.9%] in staff areas, and 15 [18.5%] in public areas). Two studies13,30 described positive viral cultures, both from the close patient environment (3 of 39 [7.7%];13 and 4 of 4 [100%]30) in a non-ICU setting.
Among studies with SARS-CoV-2 positive air samples11-13,16,17,23,30 that performed a quantitative RT-PCR, the median (interquartile range [IQR]) RNA concentrations varied from 1.0 × 103 copies/m3 (0.4 × 103 to 3.1 × 103) in clinical areas to 9.7 × 103 (5.1 × 103 to 14.3 × 103) in the air of toilets and/or bathrooms (Figure 2). The median (IQR) concentration found in close patients environments was 3.8 × 103 (1.2 × 103 to 3.3 × 103) copies/m3 (P < .001). Among the 3 studies9,13,16 that assessed the particle size in air sampled in parallel with the viral load, 1 study16 found an RNA concentration of 2.0 × 103 copies/m3 for particles greater than 4 μm and 1.3 × 103 for particles sized 1 to 4 μm in 1 patient room, and 927 and 916 copies/m3 of those sizes, respectively, in a second room, both at a distance of 1.0 to 2.1 m from patients (Figure 3). A second study9 of 2 PPE removal rooms found 40.0 × 103 and 12.0 × 103 copies/m3 for particles less than 1 μm, and 2.0 × 103 to 8.0 × 103 copies/m3 for particles sized 1 to 4 μm in 2 PPE removal rooms. A concentration of 7.0 × 103 copies/m3 was found for particles less than 1 μm and 13.0 × 103 copies/m3 for particles sized 1 to 4 μm in medical staff offices.31 For the third study that performed viral cultures with air samples from 6 different patients’ room,13 the median (IQR) viral concentration was 4.8 (3.3-5.8) TCID50/m3 for particles less than 1 μm, 4.27 (2.96-5.48) TCID50/m3 for particles sized 1 to 4 μm, and 1.82 (1.6-2.55) TCID50/m3 for particles greater than 4 μm.13
This scoping systematic review of the literature suggests that air near and distant from patient environments, including toilets and/or bathrooms, staff areas, and public areas, may carry viral RNA. However, the infectivity of the virus assessed by viral culture was only reported by 2 studies in non-ICU patient rooms. PPE removal and patient rooms had high concentrations per titer of SARS-CoV-2 with aerosol size distributions that showed peaks of particles sized less than 1 μm; for staff offices, the size distribution peaked for particles sized greater than 4 μm.
The results of positivity rate in ICU and non-ICU patient environments were highly heterogeneous and appeared superior in the ICU when pooling the results. In the ICU, 7 of 12 studies did not find SARS-CoV-2 RNA, whereas the remaining did, with 37.5% to 100% positive samples. In non-ICU patient environments, 11 of 19 did not find SARS-CoV-2 RNA, and 8 studies found viral RNA present in from 1.9% to 100% of samples. This heterogeneity may be explained either by a different case mix or by a difference in the methods used for air sampling. The level of severity of patients’ infections was not associated with increased air contamination. Several studies32,33 suggested higher viral loads might be associated with severe clinical outcomes. However, the association between clinical conditions and air contamination may be more complex. The potential opportunistic airborne contamination occurring during aerosol-generating procedures (AGPs) and ventilation at the time of sampling could inform the results. All these factors were poorly detailed in the articles analyzed. The sampling method, including the sampler used; its position in the clinical unit and in relation to patients; the duration of sampling; the volume sampled; and the conditions for transfer to the laboratory were highly variable across studies. The volume of a single room is approximately 40 m3. However, most sample volumes were less than 10 m3, at various airflow rates, for a duration of less than or equal to 1 hour, potentially not reflecting the reality of air contamination. The climatic conditions (eg, temperature and hygrometry) were poorly detailed in studies reviewed, but they may affect the capacity for viral particles to persist in the air.34 The methods for RNA detection varied, especially the cycle threshold (Ct) for PCR positivity, which also varied from 37 to 45. The RT-PCR Ct values are strongly associated with a cultivable virus. The probability of culturing virus declines to 8% in samples with Ct of greater than 35.35 Only 2 studies13,30 described a positive viral culture on samples with SARS-CoV-2 RNA on RT-PCR, suggesting that most samples did not contain enough infectious virus. Most sampling methods affect viral infectivity, which may partly explain these results.36 Future studies should consider these points for better accuracy and comparability of data.
The concentration of SARS-CoV-2 RNA in aerosols detected in isolation wards and in areas where patients were receiving ventilation was very low. However, a higher concentration of viral RNA was found in patient toilets, public areas, and in some medical staff areas. The finding of high concentrations in staff rooms (ie, meeting and dining rooms) is consistent with the possible cross-transmission of COVID-19 among HCPs during breaks. During these periods, face masks are frequently removed in small areas without ventilation. Toilets and staff rooms are often small and poorly ventilated. The presence of SARS-CoV-2 RNA in stool samples has been described in several studies.37,38 Toilet flushing may lead to the aerosolization of RNA in small and nonventilated toilets or bathrooms. In an epidemic setting, public areas are often crowded, with both a high patient flow and high incidence of COVID-19. These factors have to be considered to control the transmission of COVID-19 between nonmasked HCPs in hospitals, especially staff rooms and lockers.
Only 3 studies9,13,16 assessed the size of particles found when searching for SARS-CoV-2. Regarding aerosols of submicrometer size that were observed in PPE removal and patient rooms, the authors of those studies hypothesized the resuspension of virus-laden aerosols from the surfaces of PPE worn by medical staff. The submicrometer virus–laden aerosols may originally come from direct deposition of respiratory droplets or airborne SARS-CoV-2 from a patient to the PPE. On the other hand, floor-deposited SARS-CoV-2 could be the source of virus-laden aerosols greater than 4 μm that were then carried across different areas by medical staff.
The findings of this scoping systematic review are consistent with the accumulated knowledge on other respiratory viruses. SARS-CoV-1 is commonly recognized to be mainly transmitted through large droplets, requiring particular conditions to be airborne transmitted, such as AGPs.39,40 For other respiratory viruses, a 2019 review described the frequent presence of nucleic material (RNA or DNA) in the air around patients with influenza, respiratory syncytial virus, adenovirus, rhinovirus, and other coronaviruses but rarely the presence of viable viruses.41 The current available evidence on hospital air contamination by SARS-CoV-2 leans toward the effectiveness of surgical face masks in most circumstances to prevent cross-transmission of COVID-19 in hospital settings.42 In contrast, AGPs on the respiratory tract require wearing a respirator (N95 or FFP2) to prevent transmission and protect HCPs.5,43 However, the validation of these hypothesis regarding the transmission mode of COVID-19 and the associated efficacy of PPE requires more robust studies. A randomized clinical trial comparing the surgical face mask with respirator may provide important information for recommendations regarding respiratory protection for HCPs in settings in addition to AGPs. Assessing SARS-CoV-2 RNA and viable virus contamination of surgical face masks and respirators worn by HCP according to a panel of procedures with patients with COVID-19 would provide information on exposure in routine practice.
This study has limitations. First, the context (ie, location, ventilation, distance, and clinical context) were infrequently detailed in studies. Misclassification may have occurred when variables were categorized without enough detail. Moreover, the sampling and microbiology methods were highly heterogeneous across studies. As explained earlier, these flaws potentially affected the comparability of data and the reliability of pooled data analysis. This issue was avoided by performing categorization only when data were available. Second, for a better clarity of analysis, we did not include surface contamination. However, air and surface contamination are potentially correlated and may ease the understanding of resuspension. Third, we included articles not validated by a peer review process.
In this study, the air around patients hospitalized with COVID-19 was frequently contaminated with SARS-CoV-2 RNA but rarely with viable viruses. The available data suggest that COVID-19 requires particular conditions to be transmitted through the air (such as AGPs), leaning toward the effectiveness of surgical face masks in most circumstances. High viral loads found in toilets and/or bathrooms, staff areas, and public hallways argue for a careful consideration of these areas for the prevention of COVID-19 transmission. However, the presence of viable viruses should be primarily considered, given that it is a required link for the potential of cross-transmission.
Accepted for Publication: November 18, 2020.
Published: December 23, 2020. doi:10.1001/jamanetworkopen.2020.33232
Correction: This article was corrected on January 26, 2021, to fix an error in Figure 3.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Birgand G et al. JAMA Network Open.
Corresponding Author: Gabriel Birgand, PhD, Centre Hospitalo-Universitaire de Nantes, 5 rue du Professeur Yves Boquien, 44093 Nantes, France (firstname.lastname@example.org).
Author Contributions: Dr Birgand had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Birgand, Peiffer-Smadja, Fournier, Lucet.
Acquisition, analysis, or interpretation of data: Birgand, Peiffer-Smadja, Fournier, Kerneis, Lescure.
Drafting of the manuscript: Birgand, Fournier, Lucet.
Critical revision of the manuscript for important intellectual content: Birgand, Peiffer-Smadja, Kerneis, Lescure.
Statistical analysis: Birgand.
Supervision: Lescure, Lucet.
Conflict of Interest Disclosures: Dr Kerneis reported receiving personal fees, grants, and nonfinancial support from bioMérieux, travel fees from Accelerate Diagnostics, and personal fees from MSD outside the submitted work. Dr Lescure reported receiving personal fees from bioMérieux, Gilead, and MSD outside the submitted work. No other disclosures were reported.
Funding/Support: The research was funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London in partnership with Public Health England. The support of Economic and Social Research Council as part of the Antimicrobial Cross Council initiative supported by the 7 UK research councils and also the support of the Global Challenges Research Fund is gratefully acknowledged.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health, or Public Health England.
Meeting Presentation: These results have been presented at the virtual ESCMID Conference on Coronavirus Disease (ECCVID); September 23, 2020.
Additional Contributions: Marta Castrica, MSc (Department of Health, Animal Science and Food Safety VESPA, University of Milan, UNIMI), and Laura Menchetti, MSc (Faculty of Veterinary Medicine, Università degli Studi di Perugia, UNIPG) assisted with data collection. They were not compensated for their time.