Oxygen Therapy and Risk of Infection for Health Care Workers Caring for Patients With Viral Severe Acute Respiratory Infection: A Systematic Review and Meta-analysis

  • Alexis Cournoyer
    Correspondence
    Corresponding Author.
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux de l'Est-de-l'Île-de-Montréal, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada

    Corporation d’Urgences-santé, Montreal, Quebec, Canada
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  • Sophie Grand’Maison
    Affiliations
    Department of Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Medicine, Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada
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  • Ann-Marie Lonergan
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Justine Lessard
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Jean-Marc Chauny
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Véronique Castonguay
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Martin Marquis
    Affiliations
    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Amélie Frégeau
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Vérilibe Huard
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Zoé Garceau-Tremblay
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Ann-Sophie Turcotte
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Éric Piette
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Jean Paquet
    Affiliations
    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Sylvie Cossette
    Affiliations
    Faculty of Nursing, Université de Montréal, Montreal, Quebec, Canada

    Research Center, Institut de Cardiologie de Montréal, Montreal, Quebec, Canada
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  • Anne-Laure Féral-Pierssens
    Affiliations
    Charles Lemoyne-Saguenay-Lac-Saint-Jean Research Center on Health Innovations, Université de Sherbrooke, Longueuil, Quebec, Canada

    Department of Emergency Medicine, Hôpital Européen Georges Pompidou, Paris, France
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  • Renaud-Xavier Leblanc
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré de santé et de services sociaux de Laval, Hôpital Cité de la Santé, Laval, Quebec, Canada
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  • Valéry Martel
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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  • Raoul Daoust
    Affiliations
    Department of Family Medicine and Emergency Medicine, Université de Montréal, Montreal, Quebec, Canada

    Department of Emergency Medicine, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
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      Study objective

      To synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection. Health care workers face significant risk of infection when treating patients with a viral severe acute respiratory infection. To ensure health care worker safety and limit nosocomial transmission of such infection, it is crucial to synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection.

      Methods

      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to April 1, 2020, for studies describing the risk of infection associated with the modalities of oxygen therapy used for patients with severe acute respiratory infection. The study selection, data extraction, and quality assessment were performed by independent reviewers. The primary outcome measure was the infection of health care workers with a severe acute respiratory infection. Random-effect models were used to synthesize the extracted data.

      Results

      Of 22,123 citations, 50 studies were eligible for qualitative synthesis and 16 for meta-analysis. Globally, the quality of the included studies provided a very low certainty of evidence. Being exposed or performing an intubation (odds ratio 6.48; 95% confidence interval 2.90 to 14.44), bag-valve-mask ventilation (odds ratio 2.70; 95% confidence interval 1.31 to 5.36), and noninvasive ventilation (odds ratio 3.96; 95% confidence interval 2.12 to 7.40) were associated with an increased risk of infection. All modalities of oxygen therapy generate air dispersion.

      Conclusion

      Most modalities of oxygen therapy are associated with an increased risk of infection and none have been demonstrated as safe. The lowest flow of oxygen should be used to maintain an adequate oxygen saturation for patients with severe acute respiratory infection, and manipulation of oxygen delivery equipment should be minimized.

      Introduction

       Background

      Viral severe acute respiratory infections are infectious transmittable diseases that have pandemic potential.
      • McCloskey B.
      • Dar O.
      • Zumla A.
      • et al.
      Emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread.
      The World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern on February 11, 2020, and a pandemic on March 11, 2020.
      • Lai C.C.
      • Shih T.P.
      • Ko W.C.
      • et al.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.
      As of June 7, 2020, COVID-19 had been diagnosed in approximately 7 million patients worldwide, with the number of new cases continually increasing.

      WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 1392020. Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200607-covid-19-sitrep-139.pdf?sfvrsn=79dc6d08_2. Accessed July 26, 2020.

      What is already known on this topic
      The delivery of oxygen may create fomites and aerosols that can spread pathogens to health care workers.
      What question this study addressed
      Which oxygen delivery methods elevate the risk of respiratory pathogen transmission to bedside health care workers?
      What this study adds to our knowledge
      From a meta-analysis of 50 trials, most with bias threats, intubation carried the highest risk of potential transmission, but other methods also likely elevated risk compared with nonuse.
      How this is relevant to clinical practice
      Carefully weigh the need for oxygen and the delivery method, especially when a potentially transmissible severe viral respiratory infection is suspected.
      Severe acute respiratory infections often present with acute respiratory distress.
      • Yang X.
      • Yu Y.
      • Xu J.
      • et al.
      Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
      ,
      • Hui D.S.
      • Memish Z.A.
      • Zumla A.
      Severe acute respiratory syndrome vs the Middle East respiratory syndrome.
      Consequently, the initial treatment most often provided is oxygen therapy.
      • Yang X.
      • Yu Y.
      • Xu J.
      • et al.
      Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
      ,
      • Hui D.S.
      • Memish Z.A.
      • Zumla A.
      Severe acute respiratory syndrome vs the Middle East respiratory syndrome.
      Although some cases require early mechanical ventilation, others can be managed with supplemental oxygen alone or noninvasive ventilation.
      • Yang X.
      • Yu Y.
      • Xu J.
      • et al.
      Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
      ,
      • Rello J.
      • Rodriguez A.
      • Ibanez P.
      • et al.
      Intensive care adult patients with severe respiratory failure caused by influenza A (H1N1)v in Spain.
      Also, before intubation for mechanical ventilation, patients often need supplemental oxygen or noninvasive ventilation, and these may be the only treatments available for some patients in the midst of a pandemic, given the surge of patients in respiratory distress.
      • Rello J.
      • Rodriguez A.
      • Ibanez P.
      • et al.
      Intensive care adult patients with severe respiratory failure caused by influenza A (H1N1)v in Spain.
      ,
      • Remuzzi A.
      • Remuzzi G.
      COVID-19 and Italy: what next?.
      Some modalities of oxygen therapy have been shown to generate aerosols, which can increase severe acute respiratory infection transmission.
      • Tran K.
      • Cimon K.
      • Severn M.
      • et al.
      Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.

       Importance

      Although all health care workers face a significant risk of infection when treating patients with severe acute respiratory infection, the modality of oxygen therapy used might modify that risk.
      • Tran K.
      • Cimon K.
      • Severn M.
      • et al.
      Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.
      • McDonald L.C.
      • Simor A.E.
      • Su I.J.
      • et al.
      SARS in healthcare facilities, Toronto and Taiwan.
      Novel Coronavirus Pneumonia Emergency Response Epidemiology Team
      [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].
      • Esquinas A.M.
      • Egbert Pravinkumar S.
      • Scala R.
      • et al.
      Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review.
      Ideally, respiratory protection should be maximized for all health care workers in contact with patients, but this might not be possible during a pandemic.
      • Patel A.
      • Lee L.
      • Pillai S.K.
      • et al.
      Approach to prioritizing respiratory protection when demand exceeds supplies during an influenza pandemic: a call to action.
      A better understanding of the risk involved in providing different modalities of oxygen therapy to patients with severe acute respiratory infection would assist clinicians in selecting the most suitable approach for patients, improve the allocation of respiratory protective equipment, improve health care workers’ confidence when caring for these patients, and decrease the overall burden of these diseases.

       Goals of This Investigation

      To maximize health care worker safety and limit nosocomial transmission of severe acute respiratory infections, it is crucial to synthesize the evidence regarding the health care workers’ risk of infection when caring for patients with severe acute respiratory infection requiring oxygen therapy. Therefore, this review’s main objective was to describe the rate of health care worker severe acute respiratory infection according to the modality used to provide oxygen.

      Materials and Methods

      The present systematic review and meta-analysis was registered before its initiation. Its results are presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (Table E1, available online at http://www.annemergmed.com).
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred Reporting Items for Systematic Reviews and Meta-analyses Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

       Study Design

      The search strategy aimed to find both published and unpublished studies. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to April 1, 2020 (Appendix E1, available online at http://www.annemergmed.com). Gray literature was searched with Google Scholar. The references provided in the guidelines or the care of severe acute respiratory infection patients of major free open-access medical education blogs, global, American, and European health organizations, as well as in all previously identified articles and main review articles, were reviewed in search of additional studies. The authors of included articles were also contacted to assess whether they had access to pertinent unpublished data.
      A 3-stage selection process was used. In the first stage, after automatic removal of duplicates, each citation title was screened to exclude obviously unrelated studies. In the second stage, the titles and abstracts of the remaining citations were screened for potential relevance by pairs of independant reviewers (S.G.M. and V.M., J.L. and V.C., J.-M.C. and A.-L.F.-P., M.M. and E.P., A.F. and R.-X.L., Z.G.-T. and J.P., or A.-S.T. and R.D.). In the final stage, the full text of remaining citations was evaluated against the following inclusion and exclusion criteria by pairs of independent reviewers (A.C. and S.G.M., J.L., J.-M.C., V.C., M.M., A.F., V.H., or A.-S.T.). Discrepancies were resolved by consensus with a third reviewer (A.C. for the second stage and R.D. for the final stage).
      Inclusion criteria were original studies of all designs describing the risk (rate and total number) of infection for health care workers caring for adult patients with severe acute respiratory infection (COVID-19, severe acute respiratory syndrome, Middle East respiratory syndrome, and emerging or pandemic influenza) according to the modality of oxygen therapy provided (intubation, noninvasive ventilation [bilevel positive airway pressure {BiPAP} or continuous positive airway pressure], high-flow nasal cannula, bag-valve-mask ventilation, and face mask with or without reservoir and nasal cannula). Because it was anticipated that limited clinical data would be available for some modalities of oxygen therapy, studies on aerosol generation and droplet dispersion were also considered for inclusion. Studies describing only patients already receiving mechanical ventilation were excluded as outside the scope of this review, which focused on the oxygen therapy initially provided and also because the nature of care these patients frequently receive (eg, tracheal suctioning) is often different. Animal studies were also excluded. There were no language restrictions, but studies published before January 1, 2000, were excluded because they were published before the first modern-day severe acute respiratory infection pandemic (severe acute respiratory syndrome 2002 to 2003).
      • Zhong N.S.
      • Zheng B.J.
      • Li Y.M.
      • et al.
      Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.

       Data Collection and Processing

      The data (summary estimates) for all pertinent variables (eg, first author, publication year, study design, disease treated, number of health care workers exposed, number of patients treated, modality of oxygen therapy evaluated, health care worker infection) were extracted independently by 2 reviewers (A.C. and S.G.M.) using a standardized electronic form, with conflicts resolved through consensus. For each modality of oxygen therapy, an exposed health care worker had to have been in the room in which the oxygen therapy was provided. An unexposed health care worker had to have cared for patients with severe acute respiratory infection but must not have been present in the room while the studied modality of oxygen therapy was administered. An attempt was made to contact the authors of the included articles to ensure that the abstraction and interpretation of their data were accurate and to certify that there were no duplicate data.

       Outcome Measures

      The primary outcome measure was the development of a severe acute respiratory infection for health care workers. The preferred timing of measurement was at 14 days postexposure, given the incubation period of the diseases of interest.
      • Lai C.C.
      • Shih T.P.
      • Ko W.C.
      • et al.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.
      ,
      • Kuk A.Y.C.
      • Ma S.
      The estimation of SARS incubation distribution from serial interval data using a convolution likelihood.
      The secondary outcome measure, used for aerosol-generation models, was aerosol or exhaled air dispersion during oxygen therapy. When multiple results were presented for the same modality of oxygen therapy, the maximal dispersion distance was reported. Adjusted odds ratio (OR) was the effect measure used whenever available. If no adjusted OR was provided, unadjusted OR was used or calculated from the available data. For case reports and case series, the proportion or number of health care workers infected was described separately.
      The quality assessment of all retained articles was performed by 2 independent reviewers (A.C. and S.G.M.), with conflicts resolved through consensus. The risk of bias was evaluated with a modified Newcastle-Ottawa Scale.

      Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed July 26, 2020.

      Articles with a score of 8 or more were considered at low risk of bias, 6 or 7 at moderate risk, and 5 or less at high risk. Abstracts, case reports, case series, and models were considered at high risk of bias.

       Primary Data Analysis

      For outcomes reported in at least 3 clinical studies, results were pooled in a meta-analysis. Heterogeneity was assessed statistically with I2. If the I2 was greater than 75%, the results were described only qualitatively, without a meta-analysis. A random-effect model was used to better account for the expected differences in design among the included studies. The results are presented according to the modality of oxygen therapy provided. Results from case series, case reports, and models were not meta-analyzed and are presented after clinical results, in the appropriate subgroup of oxygen therapy. Studies in which risks for different modalities of oxygen therapy or another high-risk intervention were combined were evaluated separately (mixed exposure). All results are presented with their 95% confidence intervals (CIs).
      For each analysis in which more than 10 articles would be included, a funnel plot was constructed to assess for a publication bias.

      The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011] 2011.

      When fewer than 10 articles were available, the reporting bias was assessed qualitatively.
      In addition, 2 sets of sensitivity analyses were performed: 1 excluding articles at high risk of bias and 1 excluding studies with an n of less than 50.
      All analyses were performed with RevMan (version 5.3; Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark).

      Results

       Characteristics of Study Subjects

      Of 22,123 unique citations, 50 studies were included (Figure 1). A total of 16 observational studies (either cohort studies or case-control studies) reported clinical outcomes and were included in the meta-analysis (cohort studies 8; case-control studies 8). An additional 14 case reports or series and 20 studies reporting on aerosol or droplet dispersion were included in the systematic review. Most of the 30 clinical studies described the risk of transmission of severe acute respiratory syndrome (n=18; 60%) or influenza virus (n=7; 23%). Given the recent emergence of COVID-19, only 3 studies (10%) evaluated the infection of health care workers by the virus. A total of 16 studies presented results regarding intubation, 5 for bag-valve-mask manual ventilation, 22 for noninvasive ventilation, 9 for high-flow nasal cannula, 11 for face mask with or without reservoir, and 4 for nasal cannula. Three studies reported outcomes with the use of more than one modality of oxygen therapy or in combination with another high-risk intervention. The individual characteristics of the 50 studies included are presented in the Table. All included studies were considered at moderate (n=4) or high (n=46) risk of bias and globally provided a very low certainty of evidence (Table E2, available online at http://www.annemergmed.com). One article described the odds of having a superspreading event (3 nosocomial cases or more) in a hospital.
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      Twelve authors provided a reply and validated the extraction of their data.
      • Han F.
      • Jiang Y.Y.
      • Zheng J.H.
      • Gao Z.C.
      • He Q.Y.
      Noninvasive positive pressure ventilation treatment for acute respiratory failure in SARS.
      • Loh N.W.
      • Tan Y.
      • Taculod J.
      • et al.
      The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak.
      • Rello J.
      • Perez M.
      • Roca O.
      • et al.
      High-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza A/H1N1v.
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      • Wong B.C.
      • Lee N.
      • Li Y.
      • et al.
      Possible role of aerosol transmission in a hospital outbreak of influenza.
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      • Iwashyna T.J.
      • Boehman A.
      • Capelcelatro J.
      • et al.
      Variation in aerosol production across oxygen delivery devices in spontaneously breathing human subjects.
      • Mardimae A.
      • Slessarev M.
      • Han J.
      • et al.
      Modified N95 mask delivers high inspired oxygen concentrations while effectively filtering aerosolized microparticles.
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      • Fowler R.A.
      • Guest C.B.
      • Lapinsky S.E.
      • et al.
      Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.
      • Caputo K.M.
      • Byrick R.
      • Chapman M.G.
      • et al.
      Intubation of SARS patients: infection and perspectives of healthcare workers.
      • Park B.J.
      • Peck A.J.
      • Kuehnert M.J.
      • et al.
      Lack of SARS transmission among healthcare workers, United States.
      TableDemographics and study characteristics.
      StudyStudy DesignRisk of BiasDisease TreatedNo. of Patients TreatedNo. of HCWs ExposedModality of Oxygen Therapy AssessedHCWs Infected, %, 95% CIHCWs Who Always Wore an N95 Respirator, Equivalent, or Greater Protection While in Patient’s Room, %
      Belenguer-Muncharaz, 2011
      • Belenguer-Muncharaz A.
      • Reig-Valero R.
      • Altaba-Tena S.
      • et al.
      [Noninvasive mechanical ventilation in severe pneumonia due to H1N1 virus].
      Case seriesHighInfluenza5NACPAP, BiPAP0, NANA
      Cai, 2020
      • Cai S.J.
      • Wu L.L.
      • Chen D.F.
      • et al.
      [Analysis of bronchoscope-guided tracheal intubation in 12 cases with COVID-19 under the personal protective equipment with positive pressure protective hood].
      Case seriesHighCOVID-19129Bronchoscope-guided intubation0, 0–37100
      Caputo, 2006
      • Caputo K.M.
      • Byrick R.
      • Chapman M.G.
      • et al.
      Intubation of SARS patients: infection and perspectives of healthcare workers.
      Case seriesHighSARS3533Intubation9, 2–2591
      Chan, 2013
      • Chan M.T.
      • Chow B.K.
      • Chu L.
      • et al.
      Mask ventilation and dispersion of exhaled air.
      ModelHighBag-valve-mask ventilation
      Chan, 2018
      • Chan M.T.V.
      • Chow B.K.
      • Lo T.
      • et al.
      Exhaled air dispersion during bag-mask ventilation and sputum suctioning: implications for infection control.
      ModelHighBag-valve-mask ventilation
      Chen, 2006
      • Chen M.I.
      • Chow A.L.
      • Earnest A.
      • et al.
      Clinical and epidemiological predictors of transmission in severe acute respiratory syndrome (SARS).
      Case controlHighSARS98NAOxygen therapy (undefined)NANA
      Chen, 2009
      • Chen W.Q.
      • Ling W.H.
      • Lu C.Y.
      • et al.
      Which preventive measures might protect health care workers from SARS?.
      Case controlModerateSARSNA758Intubation12, 10–15NA
      Cheng, 2015
      • Cheng V.C.C.
      • Lee W.M.
      • Sridhar S.
      • et al.
      Prevention of nosocomial transmission of influenza A (H7N9) in Hong Kong.
      Abstract only.
      Retrospective cohortHighInfluenza182BiPAP, intubation0, 0–56
      Cheung, 2004
      • Cheung T.M.T.
      • Yam L.Y.C.
      • So L.K.Y.
      • et al.
      Effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome.
      Case seriesHighSARS20105BiPAP0, 0–4NA
      Christian, 2004
      • Christian M.D.
      • Loutfy M.
      • McDonald L.C.
      • et al.
      Possible SARS coronavirus transmission during cardiopulmonary resuscitation.
      Case seriesHighSARS19Mixed exposure22, 6–55100
      Fowler, 2004
      • Fowler R.A.
      • Guest C.B.
      • Lapinsky S.E.
      • et al.
      Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.
      Retrospective cohortHighSARS7122Intubation, BiPAP10, 5–14NA
      Ha, 2004
      • Ha L.D.
      • Bloom S.A.
      • Nguyen Q.H.
      • et al.
      Lack of SARS transmission among public hospital workers, Vietnam.
      Retrospective cohortHighSARSNA62BiPAP0, 0–731
      Han, 2004
      • Han F.
      • Jiang Y.Y.
      • Zheng J.H.
      • Gao Z.C.
      • He Q.Y.
      Noninvasive positive pressure ventilation treatment for acute respiratory failure in SARS.
      Case seriesHighSARS30NABiPAP0, NANA
      Heinzerling, 2020
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      Retrospective cohortHighCOVID-19143High-flow oxygen (undefined), face mask, NIV (undefined), bag-valve-mask ventilation, intubation7, 2–200
      Hui, 2006
      • Hui D.S.
      • Ip M.
      • Tang J.W.
      • et al.
      Airflows around oxygen masks: a potential source of infection?.
      ModelHighFace mask
      Hui, 2006
      • Hui D.S.
      • Hall S.D.
      • Chan M.T.
      • et al.
      Noninvasive positive-pressure ventilation: an experimental model to assess air and particle dispersion.
      ModelHighBiPAP
      Hui, 2011
      • Hui D.S.
      • Chow B.K.
      • Chu L.
      • et al.
      Exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula.
      ModelHighNasal cannula
      Hui, 2014
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ModelHighNasal cannula, face mask, BiPAP
      Hui, 2015
      • Hui D.S.
      • Chow B.K.
      • Lo T.
      • et al.
      Exhaled air dispersion during noninvasive ventilation via helmets and a total facemask.
      ModelHighBiPAP
      Hui, 2019
      • Hui D.S.
      • Chow B.K.
      • Lo T.
      • et al.
      Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.
      ModelHighHigh-flow nasal cannula, CPAP
      Ip, 2007
      • Ip M.
      • Tang J.W.
      • Hui D.S.C.
      • et al.
      Airflow and droplet spreading around oxygen masks: a simulation model for infection control research.
      ModelHighFace mask
      Iwashyna, 2020
      • Iwashyna T.J.
      • Boehman A.
      • Capelcelatro J.
      • et al.
      Variation in aerosol production across oxygen delivery devices in spontaneously breathing human subjects.
      ModelHighNasal cannula, face mask, high-flow nasal cannula
      Kotoda, 2020
      • Kotoda M.
      • Hishiyama S.
      • Mitsui K.
      • et al.
      Assessment of the potential for pathogen dispersal during high-flow nasal therapy.
      ModelHighHigh-flow nasal cannula
      Leonard, 2020
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      ModelHighNasal cannula, high-flow nasal cannula
      Leung, 2019
      • Leung C.C.H.
      • Joynt G.M.
      • Gomersall C.D.
      • et al.
      Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial.
      ModelHighHigh-flow nasal cannula
      Liu, 2009
      • Liu W.
      • Tang F.
      • Fang L.Q.
      • et al.
      Risk factors for SARS infection among hospital healthcare workers in Beijing: a case control study.
      Case controlModerateSARSNA477Intubation11, 8–147
      Loeb, 2004
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      Retrospective cohortModerateSARS332Face mask, BiPAP, bag-valve-mask ventilation, intubation25, 13–4250
      Loh, 2020
      • Loh N.W.
      • Tan Y.
      • Taculod J.
      • et al.
      The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak.
      ModelHighHigh-flow nasal cannula
      Luo, 2015
      • Luo Y.
      • Ou R.
      • Ling Y.
      • et al.
      [The therapeutic effect of high flow nasal cannula oxygen therapy for the first imported case of Middle East respiratory syndrome to China].
      Case reportHighMERS1NAHigh-flow nasal cannula0, NANA
      Mardimae, 2006
      • Mardimae A.
      • Slessarev M.
      • Han J.
      • et al.
      Modified N95 mask delivers high inspired oxygen concentrations while effectively filtering aerosolized microparticles.
      ModelHighFace mask
      Nam, 2017
      • Nam H.S.
      • Yeon M.Y.
      • Park J.W.
      • et al.
      Healthcare worker infected with Middle East respiratory syndrome during cardiopulmonary resuscitation in Korea, 2015.
      Case reportHighMERS16Mixed exposure17, 3–56100
      Ng, 2020
      • Ng K.
      • Poon B.H.
      • Kiat Puar T.H.
      • et al.
      COVID-19 and the risk to health care workers: a case report.
      Retrospective cohortHighCOVID-19141NIV (undefined), intubation0, 0–915
      Nishiyama, 2008
      • Nishiyama A.
      • Wakasugi N.
      • Kirikae T.
      • et al.
      Risk factors for SARS infection within hospitals in Hanoi, Vietnam.
      Retrospective cohortHighSARSNA146Oxygen therapy (undefined)29, 22–38NA
      O’Neil, 2017
      • O'Neil C.A.
      • Li J.
      • Leavey A.
      • et al.
      Characterization of aerosols generated during patient care activities.
      ModelHighBiPAP
      Park, 2004
      • Park B.J.
      • Peck A.J.
      • Kuehnert M.J.
      • et al.
      Lack of SARS transmission among healthcare workers, United States.
      Retrospective cohortHighSARS6110Mixed exposure0, 0–552
      Pei, 2006
      • Pei L.Y.
      • Gao Z.C.
      • Yang Z.
      • et al.
      Investigation of the influencing factors on severe acute respiratory syndrome among health care workers.
      Case controlModerateSARSNA443Intubation33, 29–38NA
      Raboud, 2010
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      Case controlHighSARS45624High-flow oxygen (undefined), face mask, BiPAP, bag-valve-mask ventilation, intubation4, 3–687
      Rello, 2012
      • Rello J.
      • Perez M.
      • Roca O.
      • et al.
      High-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza A/H1N1v.
      Case seriesHighInfluenza20NAHigh-flow nasal cannula0, NANA
      Roberts, 2015
      • Roberts S.
      • Kabaliuk N.
      • Spence C.J.T.
      • et al.
      Nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting.
      Abstract only.
      ModelHighHigh-flow nasal cannula
      Scales, 2003
      • Scales D.C.
      • Green K.
      • Chan A.K.
      • et al.
      Illness in intensive care staff after brief exposure to severe acute respiratory syndrome.
      Case controlHighSARS131NIV (undefined), intubation19, 8–3819
      Simonds, 2010
      • Simonds A.K.
      • Hanak A.
      • Chatwin M.
      • et al.
      Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.
      ModelHighFace mask, BiPAP
      Somogyi, 2004
      • Somogyi R.
      • Vesely A.E.
      • Azami T.
      • et al.
      Dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome.
      ModelHighFace mask
      Teleman, 2004
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      Case controlHighSARS386Oxygen therapy (undefined), intubation47, 37–5730
      Thompson, 2013
      • Thompson K.A.
      • Pappachan J.V.
      • Bennett A.M.
      • et al.
      Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic—the risk of aerosol generation during medical procedures.
      ModelHighInfluenza5Intubation
      Tonveronachi, 2011
      • Tonveronachi E.
      • Valentini I.
      • Fabiani A.
      • et al.
      Noninvasive mechanical ventilation in patients with acute respiratory failure due to H1N1 infection.
      Abstract only.
      Case seriesHighInfluenza25NABiPAP0, NANA
      Vivarelli, 2013
      • Vivarelli M.
      • Perazzo A.
      • Gatto P.
      • et al.
      Management of severe respiratory failure following influenza a H1N1 pneumonia.
      Case seriesHighInfluenza14NACPAP, BiPAP0, NANA
      Wong, 2010
      • Wong B.C.
      • Lee N.
      • Li Y.
      • et al.
      Possible role of aerosol transmission in a hospital outbreak of influenza.
      Case seriesHighInfluenza129BiPAP0, 0–15NA
      Wong, 2011
      • Wong B.
      • Lai R.
      • Chan P.
      • et al.
      A hospital outbreak of seasonal influenza involving three health care workers—implications on the optimal choice of respiratory protection.
      Abstract only.
      Case seriesHighInfluenza13NIV (undefined)100, 44–100NA
      Yu, 2007
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      Case controlHighSARSNANAOxygen therapy (undefined), face mask, BiPAP, intubationNANA
      Zhao, 2003
      • Zhao Z.
      • Zhang F.
      • Xu M.
      • et al.
      Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China.
      Case seriesHighSARS14Intubation100, 51–100NA
      HCW, Health care worker; NA, not available, CPAP, continuous positive airway pressure; SARS, severe acute respiratory syndrome; NIV, noninvasive ventilation; MERS, Middle East respiratory syndrome, -, not relevant.
      Abstract only.

       Main Results

      A total of 2,675 health care workers (10% exposed, 14% infected) were included in the 12 observational studies in the meta-analysis assessing the risk of intubation (Table E3, available online at http://www.annemergmed.com).
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      ,
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      ,
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      ,
      • Fowler R.A.
      • Guest C.B.
      • Lapinsky S.E.
      • et al.
      Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.
      ,
      • Chen W.Q.
      • Ling W.H.
      • Lu C.Y.
      • et al.
      Which preventive measures might protect health care workers from SARS?.
      • Cheng V.C.C.
      • Lee W.M.
      • Sridhar S.
      • et al.
      Prevention of nosocomial transmission of influenza A (H7N9) in Hong Kong.
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      • Liu W.
      • Tang F.
      • Fang L.Q.
      • et al.
      Risk factors for SARS infection among hospital healthcare workers in Beijing: a case control study.
      • Ng K.
      • Poon B.H.
      • Kiat Puar T.H.
      • et al.
      COVID-19 and the risk to health care workers: a case report.
      • Pei L.Y.
      • Gao Z.C.
      • Yang Z.
      • et al.
      Investigation of the influencing factors on severe acute respiratory syndrome among health care workers.
      • Scales D.C.
      • Green K.
      • Chan A.K.
      • et al.
      Illness in intensive care staff after brief exposure to severe acute respiratory syndrome.
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      In these studies, there was an association between being present at the intubation and the risk of infection among health care workers. The summary estimate for these studies yielded an OR of 5.34 (95% CI 2.44 to 11.68), with high statistical heterogeneity (I2 = 71%) (Figure E1, available online at http://www.annemergmed.com). The results presented in the study by Teleman et al
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      were discordant with the results from the other studies. The OR calculated from their results (0.68 [95% CI 0.12 to 3.91]) is very different from the OR presented in the study itself (1.5 [95% CI 0.4 to 5.4]), and no answer was received from the authors to explain that difference. For these reasons, it was decided to exclude that study from the main model. The summary estimate for the 11 remaining studies yielded an OR of 6.48 (95% CI 2.90 to 14.44), with high statistical heterogeneity (I2 = 71%) (Figure 2). The results of one aerosol dispersion model pertaining to the performance of an intubation are presented in Appendix E2 and Table E3, available online at http://www.annemergmed.com.
      Figure thumbnail gr2
      Figure 2Forest plot describing the infection risk during intubation.
      A total of 693 health care workers (18% exposed, 5% infected) were included in the 3 observational studies in the meta-analysis assessing the risk of bag-valve-mask ventilation (Table E4, available online at http://www.annemergmed.com).
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      ,
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      ,
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      In these studies, there was an association between bag-valve-mask ventilation and the risk of infection among health care workers. The summary estimate for these studies yielded an OR of 2.70 (95% CI 1.31 to 5.56), with no statistical heterogeneity (I2 = 0%) (Figure 3). The results of 2 aerosol dispersion models pertaining to the use of bag-valve-mask ventilation are presented in Appendix E2 and Table E4, available online at http://www.annemergmed.com.
      Figure thumbnail gr3
      Figure 3Forest plot describing the infection risk during bag-valve-mask ventilation.
      A total of 942 health care workers (25% exposed, 5% infected) were included in the 9 observational studies in the meta-analysis assessing the risk of being exposed to noninvasive ventilation (Table E5, available online at http://www.annemergmed.com).
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      ,
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      ,
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      ,
      • Fowler R.A.
      • Guest C.B.
      • Lapinsky S.E.
      • et al.
      Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.
      ,
      • Cheng V.C.C.
      • Lee W.M.
      • Sridhar S.
      • et al.
      Prevention of nosocomial transmission of influenza A (H7N9) in Hong Kong.
      ,
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      ,
      • Ng K.
      • Poon B.H.
      • Kiat Puar T.H.
      • et al.
      COVID-19 and the risk to health care workers: a case report.
      ,
      • Scales D.C.
      • Green K.
      • Chan A.K.
      • et al.
      Illness in intensive care staff after brief exposure to severe acute respiratory syndrome.
      ,
      • Ha L.D.
      • Bloom S.A.
      • Nguyen Q.H.
      • et al.
      Lack of SARS transmission among public hospital workers, Vietnam.
      Subgroups were created depending on the specific exposure of health care workers (BiPAP, noninvasive ventilation [undefined], and BiPAP mask manipulation). Overall, there was an association between being exposed to noninvasive ventilation and the infection risk among health care workers. The summary estimate for these studies yielded an OR of 3.96 (95% CI 2.12 to 7.40), with no statistical heterogeneity (I2 = 0%) (Figure 4). The results of 6 case series and 6 aerosol or droplet dispersion models pertaining to the use of noninvasive ventilation are presented in Appendix E2 and Table E5, available online at http://www.annemergmed.com.
      Figure thumbnail gr4
      Figure 4Forest plot describing the infection risk during noninvasive ventilation.
      No observational studies reported on the use of high-flow nasal cannula. The results of 2 case series and 7 aerosol or droplet dispersion models pertaining to the use of high-flow nasal cannula are presented in Appendix E2 and Table E6, available online at http://www.annemergmed.com.
      Seven observational studies reported on the use of conventional oxygen therapy (Table E7, available online at http://www.annemergmed.com).
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      ,
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      ,
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      ,
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      ,
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      ,
      • Chen M.I.
      • Chow A.L.
      • Earnest A.
      • et al.
      Clinical and epidemiological predictors of transmission in severe acute respiratory syndrome (SARS).
      ,
      • Nishiyama A.
      • Wakasugi N.
      • Kirikae T.
      • et al.
      Risk factors for SARS infection within hospitals in Hanoi, Vietnam.
      It was decided not to perform a meta-analysis because of the uncertainty of the specific exposure for most of these studies and the overlapping data. In one study, Yu et al
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      observed an increased risk of a superspreading event in a ward when oxygen was administered with a face mask at more than 6 L/min (OR=7.08 [95% CI 1.30 to 38.42]). In the studies by Heinzerling et al
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      and Raboud et al,
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      there was no statistically significant association between being exposed to high-flow oxygen and infection among health care workers (OR=1.39 [95% CI 0.11 to 17.24] and OR=0.39 [95% CI 0.09 to 1.66], respectively). In studies in which oxygen therapy was not defined, Chen et al
      • Chen M.I.
      • Chow A.L.
      • Earnest A.
      • et al.
      Clinical and epidemiological predictors of transmission in severe acute respiratory syndrome (SARS).
      and Yu et al
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      reported an increased risk of infection (OR=4.60 [95% CI 1.40 to 15.08] and OR=10.97 [95% CI 1.73 to 69.39], respectively), whereas Nishiyama et al
      • Nishiyama A.
      • Wakasugi N.
      • Kirikae T.
      • et al.
      Risk factors for SARS infection within hospitals in Hanoi, Vietnam.
      and Teleman et al
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      did not (OR=2.65 [95% CI 0.66 to 10.70] and OR=0.97 [95% CI 0.33 to 2.84], respectively). Three studies reported on the risk associated with manipulation of the oxygen mask.
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      ,
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      ,
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      One of these studies reported an increased risk of infection with such an exposure (OR=17.00 [95% CI 1.75 to 165.00]),
      • Loeb M.
      • McGeer A.
      • Henry B.
      • et al.
      SARS among critical care nurses, Toronto.
      whereas the results of the others did not reach statistical significance (OR=11.60 [95% CI 0.88 to 153.29]
      • Heinzerling A.
      • Stuckey M.J.
      • Scheuer T.
      • et al.
      Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
      and OR=2.14 [95% CI 0.94 to 4.89]).
      • Raboud J.
      • Shigayeva A.
      • McGeer A.
      • et al.
      Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
      The results of 9 aerosol dispersion models pertaining to the administration of conventional oxygen therapy are presented in Appendix E2 and Table E7, available online at http://www.annemergmed.com.
      No observational studies reported on the use of high-flow nasal cannula. The results of 3 case series in which a mixed exposure was observed are presented in Appendix E2 and Table E8, available online at http://www.annemergmed.com.

       Sensitivity Analyses

      Sensitivity analyses yielded no additional information. The exclusion of articles at high risk of bias did not significantly influence the results regarding the exposure to intubation (Figure E2, available online at http://www.annemergmed.com). Only one article remained available for the exposure to bag-valve-mask ventilation and noninvasive ventilation (Figures E3 and E4, available online at http://www.annemergmed.com). A publication bias might have prevented small studies without significant results regarding the exposure to intubation from being published (Figure E5, available online at http://www.annemergmed.com). A publication bias might also have prevented case series with an intermediate rate of infection from being published because only 3 of the 14 case reports and series included did not report a risk of infection of either 0% or 100%. No other evidence of a publication bias was found.

      Limitations

      The main limitation of the present review is the quality of the studies included. Most studies had significant limitations in their design and included only a small number of health care workers, of whom only a few were infected. However, the results were consistent in the sensitivity analyses in which articles at high risk of bias were excluded. Some studies did not report any infection, which prevented the calculation of an OR. Most of the clinical studies that were included described the risk of severe acute respiratory syndrome transmission. Other severe acute respiratory infections might have a different predisposition of transmission and this limits the generalizability of the presented results to the current COVID-19 pandemic. In addition, it is possible that improvement in technical aspects of oxygen therapy (eg, video-assisted rapid sequence intubation, double-limb circuit noninvasive ventilation) could decrease the risk of contamination. Although every author was contacted to validate that there were no repeated data, it remains possible that some health care workers were included in multiple studies that were conducted at the same site. There were no clinical data for some modalities of oxygen therapy, which prevented the realization of a meta-analysis and left some conclusions relying on indirect data. Finally, it is probable that the presented results were confounded to some extent by the increased disease severity and contagiousness of the patients requiring oxygen therapy, the type of personal protective equipment used by health care workers, and the infection control training they received.

      Discussion

      In this systematic review and meta-analysis, it was observed that exposure to intubation, bag-valve-mask ventilation, and noninvasive ventilation was associated with an increased risk of severe acute respiratory infection for health care workers. No clinical studies assessed the risk associated with the use of high-flow nasal cannula. The provision of conventional oxygen therapy was generally associated with an increased risk of infection even though no meta-analysis was performed, given the uncertainty of the specific exposure, the overlapping data between some studies, and the various study designs. Most models described significant air or droplet dispersion for all modalities of oxygen therapy. However, most models measuring specifically the quantity of aerosol generated did not observe a significant increase.
      The greatest risk factor for contracting a severe acute respiratory infection is probably performing or being exposed to an intubation. This had already been observed in a previous systematic review.
      • Tran K.
      • Cimon K.
      • Severn M.
      • et al.
      Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.
      Despite the high heterogeneity in the analysis, the consistency of this finding throughout studies that observed at least some infections, with the exception of the study by Teleman et al,
      • Teleman M.D.
      • Boudville I.C.
      • Heng B.H.
      • et al.
      Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
      adds some strength to that observation. As described earlier, it is possible that there was a statistical error in that study, given the discrepancy in the OR that was presented by the authors and the OR calculated from their results. The observed association is likely caused by the fact that intubation requires some proximity to the patient’s airway. Other interventions putting health care workers at risk (high-flow oxygen, airway suctioning, bag-valve-mask ventilation, chest compressions, etc) are also often performed in the context of intubation and might not have been reported while still contributing to the burden of infection associated with this procedure.
      • Christian M.D.
      • Loutfy M.
      • McDonald L.C.
      • et al.
      Possible SARS coronavirus transmission during cardiopulmonary resuscitation.
      ,
      • Nam H.S.
      • Yeon M.Y.
      • Park J.W.
      • et al.
      Healthcare worker infected with Middle East respiratory syndrome during cardiopulmonary resuscitation in Korea, 2015.
      Intubation is also frequently provided urgently for acutely ill patients, who might have higher contagiousness than their counterparts with milder symptoms. Likewise, the mental burden and stress associated with performing the intubation could increase the odds of self-contaminating during or after the procedure.
      Bag-valve-mask ventilation or noninvasive ventilation was also associated with a significantly higher risk of contagion. There was less evidence to support these findings than for intubation. The same factors as those involved in intubation support these associations. In addition, for noninvasive ventilation, the high flow and pressure of the oxygen delivered can generate jets of air and droplets, which could easily facilitate transmission of the disease.
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      No clinical evidence was available for the use of high-flow nasal cannula. One case report and one case series reported no health care worker infection with the use of this modality while patients with severe acute respiratory infection were treated.
      • Rello J.
      • Perez M.
      • Roca O.
      • et al.
      High-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza A/H1N1v.
      ,
      • Luo Y.
      • Ou R.
      • Ling Y.
      • et al.
      [The therapeutic effect of high flow nasal cannula oxygen therapy for the first imported case of Middle East respiratory syndrome to China].
      However, the air and droplet dispersion observed in some studies was similar to that observed for BiPAP, which is generally accepted as an aerosol-generating procedure.
      • Loh N.W.
      • Tan Y.
      • Taculod J.
      • et al.
      The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak.
      ,
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      ,
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      Given the observed results for other oxygenation modalities, it remains possible that contamination risk is significant when patients with severe acute respiratory infection are treated with high-flow nasal cannula.
      There was also no clinical evidence, except for higher flows of oxygen, for infection with the use of conventional oxygen therapy by face mask or nasal cannula. Air dispersion distance observed for nasal cannula at 5 L/min was, on some occasions, as high as the distance observed for BiPAP.
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      ,
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ,
      • Hui D.S.
      • Chow B.K.
      • Chu L.
      • et al.
      Exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula.
      The various air dispersion distances observed at the same flow were likely caused by a complex interaction between the patient’s physiognomy, the precise positioning of the nasal cannula, and the room configuration and ventilation.
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      ,
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ,
      • Hui D.S.
      • Chow B.K.
      • Chu L.
      • et al.
      Exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula.
      Nasal cannulae, especially at higher flows, have the potential to at least disperse naturally occurring aerosols and could even generate some aerosols in particular settings. At a similar flow, air dispersion distances were generally lower when a face mask was used rather than a nasal cannula. At a similar oxygen flow, these distances also seemed to be higher with venturi masks in comparison with simple or nonrebreather masks.
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ,
      • Ip M.
      • Tang J.W.
      • Hui D.S.C.
      • et al.
      Airflow and droplet spreading around oxygen masks: a simulation model for infection control research.
      This is likely explained by the air entrainment that increase the total air flow for venturi masks. The air dispersion distances observed for all types of face masks increased along with the oxygen flow.
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ,
      • Ip M.
      • Tang J.W.
      • Hui D.S.C.
      • et al.
      Airflow and droplet spreading around oxygen masks: a simulation model for infection control research.
      It is difficult to identify a precise cutoff that would cause aerosol generation. Yu et al
      • Yu I.T.
      • Xie Z.H.
      • Tsoi K.K.
      • et al.
      Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
      identified an increased risk of superspreading events when flows higher than 6 L/min were used. In addition, in some circumstances, with oxygen flows of 8 to 10 L/min air dispersion distances were in the range of those observed with some BiPAP settings.
      • Hui D.S.C.
      • Chan M.T.V.
      • Chow B.
      Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
      ,
      • Ip M.
      • Tang J.W.
      • Hui D.S.C.
      • et al.
      Airflow and droplet spreading around oxygen masks: a simulation model for infection control research.
      Because air dispersion distances are also likely affected by complex mask-patient-room interactions, oxygen flows higher than 6 L/min should be used with more caution by health care workers. Oxygen delivery with a face mask could also be preferred to the use of a nasal cannula.
      It remains hypothetical that any of the increased risk observed was caused by “aerosol generation.”
      • Iwashyna T.J.
      • Boehman A.
      • Capelcelatro J.
      • et al.
      Variation in aerosol production across oxygen delivery devices in spontaneously breathing human subjects.
      ,
      • Roberts S.
      • Kabaliuk N.
      • Spence C.J.T.
      • et al.
      Nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting.
      Although some studies have reported probable aerosol transmission in wards, the main route of transmission for severe acute respiratory infection might be droplets and fomites, which are spread out when these modalities of oxygen therapy are used.
      • Loh N.W.
      • Tan Y.
      • Taculod J.
      • et al.
      The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak.
      ,
      • Leonard S.
      • Atwood Jr., C.W.
      • Walsh B.K.
      • et al.
      Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
      ,
      • Wong B.C.
      • Lee N.
      • Li Y.
      • et al.
      Possible role of aerosol transmission in a hospital outbreak of influenza.
      ,
      • Yu I.T.
      • Wong T.W.
      • Chiu Y.L.
      • et al.
      Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients.
      ,
      • Simonds A.K.
      • Hanak A.
      • Chatwin M.
      • et al.
      Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.
      It is also possible that naturally occurring aerosols can be dispersed by the flow of oxygen and contaminate health care workers more easily.
      • Lindsley W.G.
      • Blachere F.M.
      • Thewlis R.E.
      • et al.
      Measurements of airborne influenza virus in aerosol particles from human coughs.
      • Lindsley W.G.
      • Blachere F.M.
      • Davis K.A.
      • et al.
      Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic.
      • Guo Z.D.
      • Wang Z.Y.
      • Zhang S.F.
      • et al.
      Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020.
      • Blachere F.M.
      • Lindsley W.G.
      • Pearce T.A.
      • et al.
      Measurement of airborne influenza virus in a hospital emergency department.
      • Milton D.K.
      • Fabian M.P.
      • Cowling B.J.
      • et al.
      Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks.
      The precautionary principle would suggest maximizing health care worker training and protection to the extent possible when patients with severe acute respiratory infection are treated, keeping in mind the limited quantities of such specialized equipment and the hierarchy of risk described previously. The present review can contribute to the complex decision facing clinicians regarding the optimal modality of oxygen therapy for patients with severe acute respiratory infection by providing a better understanding of the risk involved, which can improve health care worker safety and contribute to preserving health care system capacity, thus reducing the global morbidity associated with severe acute respiratory infection. In general, the lowest flow of oxygen should be used to maintain an adequate oxygen saturation for patients with severe acute respiratory infection, and manipulation of oxygen delivery equipment should be minimized to limit the risk of infection among health care workers.
      In summary, most modalities of oxygen therapy are associated with an increased risk of infection in health care workers and none are demonstrated as safe. Better-designed studies would improve the certainty of these observations, particularly for the modalities for which clinical data were lacking. Future studies should also evaluate whether adequate protection and training can mitigate the increased risks of transmission described in the present review.
      The authors acknowledge Monique Clar, BSc, for her help in designing the search strategy and Massimiliano Iseppon, MD, Marie-Claude Béland, MA, and Wes Martin, BSc, for their revision of the article. This project received funding from the Fonds des Urgentistes de l’Hôpital du Sacré-Cœur de Montréal, Canada.

      Supplementary Data

      • Appendix E1

        Search Terms

        Appendix E2. Supplementary results

        Table E1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist

        Figure E1. Forest plot describing the infection risk during endotracheal intubation, including the study by Teleman et al

        Figure E2. Forest plot describing the infection risk during endotracheal intubation, excluding articles at high risk of bias

        Figure E3. Forest plot describing the infection risk during bag-valve-mask ventilation, excluding articles at high risk of bias

        Figure E4. Forest plot describing the infection risk during non-invasive ventilation, excluding articles at high risk of bias

        Figure E5. Funnel plot for the evaluation of publication bias for endotracheal intubation

        Table E2. Quality Assessment and Risk of Bias

        Table E3. Infection risk during endotracheal intubation

        Table E4. Infection risk during bag-valve-mask ventilation

        Table E5. Infection risk during non-invasive ventilation

        Table E6: Infection risk with high-flow nasal cannula

        Table E7. Infection risk during conventional oxygen therapy

        Table E8: Infection risk during mixed exposure

      References

        • McCloskey B.
        • Dar O.
        • Zumla A.
        • et al.
        Emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread.
        Lancet Infect Dis. 2014; 14: 1001-1010
        • Lai C.C.
        • Shih T.P.
        • Ko W.C.
        • et al.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.
        Int J Antimicrob Agents. 2020; 55: 105924
      1. WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 1392020. Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200607-covid-19-sitrep-139.pdf?sfvrsn=79dc6d08_2. Accessed July 26, 2020.

        • Yang X.
        • Yu Y.
        • Xu J.
        • et al.
        Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
        Lancet Respir Med. 2020; 8: 475-481
        • Hui D.S.
        • Memish Z.A.
        • Zumla A.
        Severe acute respiratory syndrome vs the Middle East respiratory syndrome.
        Curr Opin Pulm Med. 2014; 20: 233-241
        • Rello J.
        • Rodriguez A.
        • Ibanez P.
        • et al.
        Intensive care adult patients with severe respiratory failure caused by influenza A (H1N1)v in Spain.
        Crit Care. 2009; 13: R148
        • Remuzzi A.
        • Remuzzi G.
        COVID-19 and Italy: what next?.
        Lancet. 2020; 395: 1225-1228
        • Tran K.
        • Cimon K.
        • Severn M.
        • et al.
        Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.
        PLoS One. 2012; 7e35797
        • McDonald L.C.
        • Simor A.E.
        • Su I.J.
        • et al.
        SARS in healthcare facilities, Toronto and Taiwan.
        Emerg Infect Dis. 2004; 10: 777-781
        • Novel Coronavirus Pneumonia Emergency Response Epidemiology Team
        [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].
        Zhonghua Liu Xing Bing Xue Za Zhi. 2020; 41: 145-151
        • Esquinas A.M.
        • Egbert Pravinkumar S.
        • Scala R.
        • et al.
        Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review.
        Eur Respir Rev. 2014; 23: 427-438
        • Patel A.
        • Lee L.
        • Pillai S.K.
        • et al.
        Approach to prioritizing respiratory protection when demand exceeds supplies during an influenza pandemic: a call to action.
        Health Secur. 2019; 17: 152-155
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • et al.
        • Preferred Reporting Items for Systematic Reviews and Meta-analyses Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        BMJ. 2009; 339: b2535
        • Zhong N.S.
        • Zheng B.J.
        • Li Y.M.
        • et al.
        Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.
        Lancet. 2003; 362: 1353-1358
        • Kuk A.Y.C.
        • Ma S.
        The estimation of SARS incubation distribution from serial interval data using a convolution likelihood.
        Stat Med. 2005; 24: 2525-2537
      2. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed July 26, 2020.

      3. The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011] 2011.

        • Yu I.T.
        • Xie Z.H.
        • Tsoi K.K.
        • et al.
        Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?.
        Clin Infect Dis. 2007; 44: 1017-1025
        • Han F.
        • Jiang Y.Y.
        • Zheng J.H.
        • Gao Z.C.
        • He Q.Y.
        Noninvasive positive pressure ventilation treatment for acute respiratory failure in SARS.
        Sleep Breath. 2004; 8: 97-106
        • Loh N.W.
        • Tan Y.
        • Taculod J.
        • et al.
        The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak.
        Can J Anaesth. 2020;
        • Rello J.
        • Perez M.
        • Roca O.
        • et al.
        High-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza A/H1N1v.
        J Crit Care. 2012; 27: 434-439
        • Leonard S.
        • Atwood Jr., C.W.
        • Walsh B.K.
        • et al.
        Preliminary findings of control of dispersion of aerosols and droplets during high velocity nasal insufflation therapy using a simple surgical mask: implications for high flow nasal cannula.
        Chest. 2020;
        • Wong B.C.
        • Lee N.
        • Li Y.
        • et al.
        Possible role of aerosol transmission in a hospital outbreak of influenza.
        Clin Infect Dis. 2010; 51: 1176-1183
        • Raboud J.
        • Shigayeva A.
        • McGeer A.
        • et al.
        Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
        PLoS One. 2010; 5e10717
        • Iwashyna T.J.
        • Boehman A.
        • Capelcelatro J.
        • et al.
        Variation in aerosol production across oxygen delivery devices in spontaneously breathing human subjects.
        2020
        • Mardimae A.
        • Slessarev M.
        • Han J.
        • et al.
        Modified N95 mask delivers high inspired oxygen concentrations while effectively filtering aerosolized microparticles.
        Ann Emerg Med. 2006; 48 (399.e391-392): 391-399
        • Loeb M.
        • McGeer A.
        • Henry B.
        • et al.
        SARS among critical care nurses, Toronto.
        Emerg Infect Dis. 2004; 10: 251-255
        • Fowler R.A.
        • Guest C.B.
        • Lapinsky S.E.
        • et al.
        Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.
        Am J Respir Crit Care Med. 2004; 169: 1198-1202
        • Caputo K.M.
        • Byrick R.
        • Chapman M.G.
        • et al.
        Intubation of SARS patients: infection and perspectives of healthcare workers.
        Can J Anaesth. 2006; 53: 122-129
        • Park B.J.
        • Peck A.J.
        • Kuehnert M.J.
        • et al.
        Lack of SARS transmission among healthcare workers, United States.
        Emerg Infect Dis. 2004; 10: 244-248
        • Chen W.Q.
        • Ling W.H.
        • Lu C.Y.
        • et al.
        Which preventive measures might protect health care workers from SARS?.
        BMC Public Health. 2009, 81; 9
        • Cheng V.C.C.
        • Lee W.M.
        • Sridhar S.
        • et al.
        Prevention of nosocomial transmission of influenza A (H7N9) in Hong Kong.
        J Hosp Infect. 2015; 90: 355-356
        • Heinzerling A.
        • Stuckey M.J.
        • Scheuer T.
        • et al.
        Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient: Solano County, California, February 2020.
        MMWR Morb Mortal Wkly Rep. 2020; 69: 472-476
        • Liu W.
        • Tang F.
        • Fang L.Q.
        • et al.
        Risk factors for SARS infection among hospital healthcare workers in Beijing: a case control study.
        Trop Med Int Health. 2009; 14: 52-59
        • Ng K.
        • Poon B.H.
        • Kiat Puar T.H.
        • et al.
        COVID-19 and the risk to health care workers: a case report.
        Ann Intern Med. 2020;172:766-767;
        • Pei L.Y.
        • Gao Z.C.
        • Yang Z.
        • et al.
        Investigation of the influencing factors on severe acute respiratory syndrome among health care workers.
        Beijing Da Xue Xue Bao Yi Xue Ban. 2006; 38: 271-275
        • Scales D.C.
        • Green K.
        • Chan A.K.
        • et al.
        Illness in intensive care staff after brief exposure to severe acute respiratory syndrome.
        Emerg Infect Dis. 2003; 9: 1205-1210
        • Teleman M.D.
        • Boudville I.C.
        • Heng B.H.
        • et al.
        Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.
        Epidemiol Infect. 2004; 132: 797-803
        • Ha L.D.
        • Bloom S.A.
        • Nguyen Q.H.
        • et al.
        Lack of SARS transmission among public hospital workers, Vietnam.
        Emerg Infect Dis. 2004; 10: 265-268
        • Chen M.I.
        • Chow A.L.
        • Earnest A.
        • et al.
        Clinical and epidemiological predictors of transmission in severe acute respiratory syndrome (SARS).
        BMC Infect Dis. 2006; 6: 151
        • Nishiyama A.
        • Wakasugi N.
        • Kirikae T.
        • et al.
        Risk factors for SARS infection within hospitals in Hanoi, Vietnam.
        Jpn J Infect Dis. 2008; 61: 388-390
        • Christian M.D.
        • Loutfy M.
        • McDonald L.C.
        • et al.
        Possible SARS coronavirus transmission during cardiopulmonary resuscitation.
        Emerg Infect Dis. 2004; 10: 287-293
        • Nam H.S.
        • Yeon M.Y.
        • Park J.W.
        • et al.
        Healthcare worker infected with Middle East respiratory syndrome during cardiopulmonary resuscitation in Korea, 2015.
        Epidemiol Health. 2017; 39e2017052
        • Hui D.S.C.
        • Chan M.T.V.
        • Chow B.
        Aerosol dispersion during various respiratory therapies: a risk assessment model of nosocomial infection to health care workers.
        Hong Kong Med J. 2014; 20: 9-13
        • Luo Y.
        • Ou R.
        • Ling Y.
        • et al.
        [The therapeutic effect of high flow nasal cannula oxygen therapy for the first imported case of Middle East respiratory syndrome to China].
        Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015; 27: 841-844
        • Hui D.S.
        • Chow B.K.
        • Chu L.
        • et al.
        Exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula.
        Respirology. 2011; 16: 1005-1013
        • Ip M.
        • Tang J.W.
        • Hui D.S.C.
        • et al.
        Airflow and droplet spreading around oxygen masks: a simulation model for infection control research.
        Am J Infect Control. 2007; 35: 684-689
        • Roberts S.
        • Kabaliuk N.
        • Spence C.J.T.
        • et al.
        Nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting.
        J Crit Care. 2015; 30: 842
        • Yu I.T.
        • Wong T.W.
        • Chiu Y.L.
        • et al.
        Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients.
        Clin Infect Dis. 2005; 40: 1237-1243
        • Simonds A.K.
        • Hanak A.
        • Chatwin M.
        • et al.
        Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.
        Health Technol Assess. 2010; 14: 131-172
        • Lindsley W.G.
        • Blachere F.M.
        • Thewlis R.E.
        • et al.
        Measurements of airborne influenza virus in aerosol particles from human coughs.
        PLoS One. 2010; 5e15100
        • Lindsley W.G.
        • Blachere F.M.
        • Davis K.A.
        • et al.
        Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic.
        Clin Infect Dis. 2010; 50: 693-698
        • Guo Z.D.
        • Wang Z.Y.
        • Zhang S.F.
        • et al.
        Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020.
        Emerg Infect Dis. 2020; (1586-1591): 26
        • Blachere F.M.
        • Lindsley W.G.
        • Pearce T.A.
        • et al.
        Measurement of airborne influenza virus in a hospital emergency department.
        Clin Infect Dis. 2009; 48: 438-440
        • Milton D.K.
        • Fabian M.P.
        • Cowling B.J.
        • et al.
        Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks.
        PLoS Pathog. 2013; 9e1003205
        • Belenguer-Muncharaz A.
        • Reig-Valero R.
        • Altaba-Tena S.
        • et al.
        [Noninvasive mechanical ventilation in severe pneumonia due to H1N1 virus].
        Med Intensiva. 2011; 35: 470-477
        • Cai S.J.
        • Wu L.L.
        • Chen D.F.
        • et al.
        [Analysis of bronchoscope-guided tracheal intubation in 12 cases with COVID-19 under the personal protective equipment with positive pressure protective hood].
        Zhonghua Jie He He Hu Xi Za Zhi. 2020; 43: E033
        • Chan M.T.
        • Chow B.K.
        • Chu L.
        • et al.
        Mask ventilation and dispersion of exhaled air.
        Am J Respir Crit Care Med. 2013; 187: e12-e14
        • Chan M.T.V.
        • Chow B.K.
        • Lo T.
        • et al.
        Exhaled air dispersion during bag-mask ventilation and sputum suctioning: implications for infection control.
        Sci Rep. 2018; 8: 198
        • Cheung T.M.T.
        • Yam L.Y.C.
        • So L.K.Y.
        • et al.
        Effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome.
        Chest. 2004; 126: 845-850
        • Hui D.S.
        • Ip M.
        • Tang J.W.
        • et al.
        Airflows around oxygen masks: a potential source of infection?.
        Chest. 2006; 130: 822-826
        • Hui D.S.
        • Hall S.D.
        • Chan M.T.
        • et al.
        Noninvasive positive-pressure ventilation: an experimental model to assess air and particle dispersion.
        Chest. 2006; 130: 730-740
        • Hui D.S.
        • Chow B.K.
        • Lo T.
        • et al.
        Exhaled air dispersion during noninvasive ventilation via helmets and a total facemask.
        Chest. 2015; 147: 1336-1343
        • Hui D.S.
        • Chow B.K.
        • Lo T.
        • et al.
        Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.
        Eur Respir J. 2019; 53 (P1802339)
        • Kotoda M.
        • Hishiyama S.
        • Mitsui K.
        • et al.
        Assessment of the potential for pathogen dispersal during high-flow nasal therapy.
        J Hosp Infect. 2020; 104: 534-537
        • Leung C.C.H.
        • Joynt G.M.
        • Gomersall C.D.
        • et al.
        Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial.
        J Hosp Infect. 2019; 101: 84-87
        • O'Neil C.A.
        • Li J.
        • Leavey A.
        • et al.
        Characterization of aerosols generated during patient care activities.
        Clin Infect Dis. 2017; 65: 1335-1341
        • Somogyi R.
        • Vesely A.E.
        • Azami T.
        • et al.
        Dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome.
        Chest. 2004; 125: 1155-1157
        • Thompson K.A.
        • Pappachan J.V.
        • Bennett A.M.
        • et al.
        Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic—the risk of aerosol generation during medical procedures.
        PLoS One. 2013; 8e56278
        • Tonveronachi E.
        • Valentini I.
        • Fabiani A.
        • et al.
        Noninvasive mechanical ventilation in patients with acute respiratory failure due to H1N1 infection.
        Eur Respir J. 2011; 38: 2968
        • Vivarelli M.
        • Perazzo A.
        • Gatto P.
        • et al.
        Management of severe respiratory failure following influenza a H1N1 pneumonia.
        Ital J Med. 2013; 7: 293-299
        • Wong B.
        • Lai R.
        • Chan P.
        • et al.
        A hospital outbreak of seasonal influenza involving three health care workers—implications on the optimal choice of respiratory protection.
        BMC Proc. 2011; 5: 100
        • Zhao Z.
        • Zhang F.
        • Xu M.
        • et al.
        Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China.
        J Med Microbiol. 2003; 52: 715-720