Risk Of Transmitting Coronavirus Disease 2019 During Nebulizer Treatment: A Systematic Review

Rationale: There is an urgent need to understand the risk of viral transmission during nebulizer treatment of patients with coronavirus disease 2019 (COVID-19).Objectives: To assess the risk of transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS, Middle East respiratory syndrome (MERS), and influenza with administration of drugs via nebulizer.Methods: We searched multiple electronic databases, including PubMed (R), China National Knowledge Infrastructure, Wanfang, preprint databases, and clinicaltrials.gov through December 1, 2020. Any study design in any language describing the risk of viral transmission with nebulizer treatment was eligible. Data were abstracted by one investigator and verified by a second.Results: We identified 22 articles: 1 systematic review, 7 cohort/case-control studies, 7 case series, and 7 simulation-based studies. Eight individual studies involved patients with SARS, five involved MERS, and one involved SARS-CoV-2. The seven cohort/case-control studies (four high risk of bias [ROB], three unclear ROB) found mixed results (median odds ratio 3.91, range 0.08-20.67) based on very weak data among a small number of health care workers (HCWs) with variable use of personal protective equipment (PPE). Case series had multiple potential contributors to transmission. Simulation studies found evidence for droplet dispersion after saline nebulization and measureable influenza viral particles up to 1.7m from the source after 10 minutes of nebulization with a patient simulator. Study heterogeneity prevented meta-analysis.Conclusions: Case series raise concern of transmission risk, and simulation studies demonstrate droplet dispersion with virus recovery, but specific evidence that exposure to nebulizer treatment increases transmission of coronaviruses similar to COVID-19 is inconclusive. Tradeoffs balancing HCW safety and patient appropriateness can potentially minimize risk, including choice of delivery method for inhaled medications (e.g., nebulizer vs. metered dose inhaler) and PPE (e.g., N95 vs. surgical mask).