As the global spread of novel coronavirus (SARS-CoV-2) continues to escalate, so has the demand for personal protective equipment (PPE), creating global shortages in the supply of N95 filtering face respirators (FFRs) and surgical masks. N95 FFRs are recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) for use by healthcare providers (HCPs) caring for coronavirus disease (COVID-19) patients requiring airborne precautions and during aerosol-generating procedures [1, 2] . Therefore, N95 FFRs are most commonly needed for HCPs in acute care and inpatient settings.
In contrast, surgical masks are recommended for use by HCPs to protect against the risk of droplet transmission in a broader range of inpatient healthcare settings, as well as outpatient settings (e.g. COVID-19 assessment centres, long-term care facilities, and community care settings) [2] [3] [4] . As the supply of N95 FFRs is threatened, HCPs may resort to use of surgical masks for airborne precautions [3, [5] [6] [7] . Surgical masks are also recommended for use by patients with suspected or confirmed COVID-19 to prevent potential spread in a variety of healthcare settings [2, 4] . Several institutions now recommend that everyone entering the hospital setting wear a surgical mask [8] .
These practices have created an unprecedented demand for surgical masks; unfortunately, the capacity for surge production of PPE is not sustainable in the long-term [5] [6] [7] . As most facemask PPE are designed for single-use, mask rationing and conservation is now a top priority globally [9] . Mask reuse is now suggested as a crisis capacity strategy to conserve available supplies during a pandemic [2, [9] [10] [11] , and much attention has now turned to decontaminating facemasks. Several strategies have been evaluated, including ultraviolet germicidal irradiation (UVGI), chemical disinfectants, and microwave-and heat-based methods; however, most of this literature has focussed on the decontamination of N95 FFRs [12] [13] [14] .
The evidence on the efficacy and safety of decontamination and reuse of surgical masks is unclear. The objective of this systematic review was to evaluate and synthesize the evidence on decontamination interventions for the purpose of surgical mask PPE reuse.
This systematic review protocol was designed a priori, registered on PROSPERO (April 15 th , 2020; CRD42020178290), and uploaded as a pre-print on Open Science Framework (April 8 th , 2020; https://osf.io/8wt37/) [15] . The reporting of this systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Appendix A) [16] .
Studies were eligible for inclusion if the following criteria were met: 1) The study was original research, including systematic reviews; 2) The study evaluated surgical facemask PPE or their components; 3) The study evaluated any intervention(s) to decontaminate, sterilize or treat surgical masks (applied either before or after their use) for the purposes of reuse as PPE; 4) At least one of the following efficacy or safety outcomes of interest was reported: a) mask performance (i.e. filtration efficiency and airflow resistance); b) reduction in pathogen load; c) in vivo infection rates following use of decontaminated masks; d) changes in physical appearance (i.e. mask appearance or physical degradation); e) adverse effects experienced by the wearer (e.g. skin irritation); or f) feasibility of the intervention (e.g. time, cost, resource utilization). We excluded editorials, case reports, narrative reviews, study protocols, clinical practice guidelines, grey literature, book chapters, and patents.
Two health sciences librarians (LS, MS) searched the following electronic databases from their dates of inception to April 8 th Citations were imported into Endnote and duplicates were removed.
Citations were uploaded to insightScope (www.insightscope.ca) for title/abstract screening and full text review. Citation screening for title/abstract and full text review stages was conducted independently and in duplicate by a team of 11 reviewers recruited from McMaster University, the University of Ottawa, and the University of Manitoba. Prior to gaining access to the full set of citations, each reviewer read the systematic review protocol and was required to achieve a sensitivity of at least 80% when screening a test set of 50 citations (containing five true positives and 45 true negatives). Reviewers achieving less than 80% sensitivity on the test set were provided with additional training. At both title/abstract and full text review, citations were excluded only if both reviewers agreed to exclude; disagreements were resolved by the study leads (DZ, KC) where necessary. Upon completion of full text review, the study co-lead (DZ) reviewed all retained citations to identify potential duplicates and confirm eligibility. The reference lists of all citations included for full text review were searched for potential eligible citations that may have evaded the initial database search.
Data were collected using electronic data extraction forms (Microsoft Excel) modified from previous systematic reviews [12, 13] for this protocol and piloted by two investigators (DZ, SG) on two eligible studies. Data was extracted from the full text publication and any related publications, referenced published protocols, or supplementary materials. Data extraction was completed in duplicate by two independent reviewers. Where necessary, graphical data was extracted using SourceForge Plot Digitizer (http://plotdigitizer.sourceforge.net) and checked by the second reviewer for accuracy. Disagreements were resolved by the study leads (DZ, KC), where necessary.
We planned to use recommended risk of bias tools where appropriate [17] ; however, in the absence of a standard risk of bias tool for laboratory studies, we applied objective assessment criteria developed for this purpose [14] . Risk of bias was assessed by two reviewers independently and in duplicate at the study level by outcome in the following domains: study design, methodological consistency, population heterogeneity, sampling bias, outcome evaluation, and selective reporting (Appendix C).
The primary outcome for this study was efficacy and safety of the decontamination intervention, as determined by any of the following: mask performance (filtration efficiency [FE] and airflow resistance); reduction in pathogen load; in vivo infection rates following use of treated masks; mask appearance or physical degradation; or adverse effects experienced by the wearer. FE refers to the percentage of particles filtered at either a specific particle size or a range of particle sizes depending on the testing agent and standard used [18] . Study results reporting percentage particle penetration were converted to FE units (i.e. FE% = 100 -particle penetration) for comparability [18] . Airflow resistance is measured as the pressure drop across the mask, quantifying initial resistance to airflow in millimetres of water column height pressure per square centimeter (mmH 2 O/cm 2 ) [19] . Reduction in pathogen load was reported as a log10 reduction factor from a time zero post-inoculation to a subsequently measured time point. If log10 reductions were not reported by the study, we calculated them using the study data provided (e.g. colony counts), where possible. A log10 reduction factor ≥ 3 was used as a reference indicating good germicidal effect [20] . The secondary outcome was feasibility of the intervention, such as the time, cost and resources required to implement the intervention.
Where results were presented for multiple experimental conditions, we reported the summary of results conducted at the harshest testing conditions, to allow a conservative interpretation of the outcomes evaluated [18] .
Primary outcome data was analysed descriptively and presented using absolute values and as a percent change where possible. No three studies evaluated the same intervention, nor applied similar test agents or conditions when evaluating outcomes. This precluded our planned quantitative analysis of outcomes [15] ; therefore, selected results from included studies were summarized descriptively.
Nine of 11 reviewers achieved the 80% sensitivity threshold on the test set. The two reviewers who did not achieve the 80% threshold were provided additional training regarding the screening protocol prior to citation screening. The review team achieved kappa values of 0.38 and 0.43 for title/abstract and full text screening respectively. Study leads resolved conflicts in 3.0% title/abstract and 12.1% full text screening citations.
Of 2191 records identified through the initial database search, 1874 unique citations were reviewed and 33 full-texts were assessed for eligibility. Twenty-six full texts were excluded for ineligibility, leaving seven unique studies for inclusion in our analysis (PRISMA diagram, Figure   1 ). No additional citations were identified on review of reference lists.
Characteristics of included studies are summarized in Table I . Only one of the seven included studies evaluated interventions applied after surgical mask use (i.e. decontamination interventions) [21] . The remaining six studies evaluated interventions applied to masks or mask components prior to use to enhance antimicrobial properties and/or FE for potential reuse or extended use (i.e. pre-contamination interventions) [22] [23] [24] [25] [26] [27] . Interventions in these studied were tested on whole masks, pieces of whole masks (referred hereafter as mask pieces) or pieces of individual mask layers (referred hereafter as mask layer pieces). Risk of bias assessments for the included studies are described in Appendix D.
Lin et al.
[21] evaluated five decontamination interventions on mask pieces of two surgical mask types commonly used in Taiwanese hospitals (gauze double-layer electret masks and Oimo spunlace non-woven masks; models unspecified): dry heat (via rice cooker), high-pressure moist heat (i.e. autoclave), and three chemical agents (70% ethanol, 100% isopropanol, and 0.5% sodium hypochlorite [i.e. bleach]). Study methods and findings are summarized in Table II . Mask pieces were assessed for FE, airflow resistance, and physical characteristics following decontamination. FE was presented graphically for a range of particle sizes (0.0146μm to 0.594μm); we summarized the results for FE at 0.1μm, a standard particle size for particulate FE testing [18] . At baseline, gauze and spunlace mask pieces had FEs of approximately 87% and 45%, respectively. FE in both mask pieces decreased after each decontamination intervention, but dry heat decontamination of gauze mask pieces demonstrated the smallest change (absolute FE reduction of 1.3%). Moist heat and chemical decontamination interventions all resulted in greater absolute FE reductions (12% to 36%). Bleach was the most damaging method, resulting in a 15.3% absolute FE reduction in spunlace mask pieces and destruction of gauze mask pieces.
Airflow resistance was assessed at a flow rate of 5.95 L/min [21] . Statistically significant changes in pressure drop were reported following all decontamination interventions, except for dry heat and ethanol on gauze mask pieces [21] . Airflow resistance results were not reported for bleach on gauze mask pieces (mask destroyed), or isopropanol for either mask type. Physical characteristics were reported only for gauze mask pieces; the autoclave deformed and caused observable folds in the mask filter, and bleach destroyed the mask. Physical characteristics following decontamination with other interventions, or in spunlace mask pieces, were not reported.
Germicidal effects of the five decontamination methods were not assessed.
Six studies evaluated five unique pre-contamination methods applied prior to mask use: four were antimicrobial interventions (nanoparticle emulsion [23, 24] , quaternary ammonium agent 
Five studies evaluated the effects of their intervention on FE, airflow resistance, or both, applying different testing techniques (Table III) evaluated FE of GS5-coated mask layer pieces using aerosolized bacteria (0.5μm to 2.1μm particle diameter) and GS5-coated masks using NaCl (0.075μm particle diameter), respectively.
They found no statistically significant change in FE in GS5-coated masks or mask layer pieces (0.6% to 1.8% FE increase in polypropylene filter layer, 1.8% FE reduction in mask; p=NS). Li et al.
[24] used a potassium-fluorescein solution (particle size not reported) to evaluate FE in nanoparticle-coated full masks by: 1) the percentage potassium content of each mask layer relative to the potassium content of the whole mask; and 2) a seven point scale rating fluorescent stains on mask users faces. They found that the percentage potassium content of each mask layer was similar compared to uncoated masks (+2%, -3% and +1.5% absolute difference from control for outer, middle and interior mask layers, respectively), and similar ratings of fluorescent stains.
Airflow resistance was non-significantly increased (+1.4 ml/s/cm 2 ; p=NS). Shen et al. [26] used an aerosolized pathogen simulant (1.0μm particle diameter) and also quantified FE as the proportion of particle content on each mask layer to that of the whole mask. They reported significant decreases in particle content on the repellant-coated outer mask layer coated with repellant (p<0.0001), but no changes to particle content on mask layers proceeding the filter layer (suggesting no changes to FE of the mask as a whole). Airflow resistance was not assessed. (Table III) however, the germicidal effect of dry heat in surgical masks is unclear. Bleach is not a safe method of decontaminating surgical masks; mask performance is significantly altered and safety data from N95 FFR studies suggest potential health risks associated with off-gassing [14] . With respect to pre-contamination interventions, salt film, GS5, nanoparticle emulsion and N-halamine mask coatings were reported not to have detrimental effects on mask performance. N-halamine and nanoparticle emulsion showed strong germicidal effects in masks (log10 reduction factors ≥ 3), which is consistent with their application in medical devices [34] , and food and water treatment [35] . Salt films also demonstrated strong germicidal effects, but their application has been experimental to date [25] . An important consideration is that pathogen load was evaluated at different post-inoculation incubation time points in each study (i.e. 5 minutes to 24 hours); it is well-established that viral load reductions can occur by virtue of time [36] .
Ideal PPE decontamination methods should not only demonstrate effective reductions in pathogen load, but also preserve mask performance without causing any residual chemical hazard to the wearer [37] . Results of included studies should be interpreted cautiously for the following reasons: 1) some of the mask types used in these experiments appear to have baseline FEs below reference standards which may have affected the results observed [18] ; 2) experiments and test conditions applied to mask pieces or individual layers cannot necessarily be extrapolated to whole masks; and 3) testing methods and outcome assessments were heterogenous. Unlike N95 FFRs, surgical masks are not certified under standardized National Institute for Occupational Safety and Health regulations. The Food and Drug Administration (FDA) recommends that several standards (ASTM F2101, ASTM 2299, Mil-M369454C, or modified Greene and Vesley method) may be applied to surgical masks, complicating the evaluation of mask performance in this review [18] . There are many test conditions that can impact FE, such as particle size, particle charge (i.e. whether charge neutralized or not), and face velocity (i.e. flow rate); however, the FDA and ASTM do not have uniform recommended standards [18] . The evidence that we have collated in this systematic review is therefore important and essential.
This systematic review reveals that the body of evidence on decontamination interventions for surgical masks is scant compared to N95 FFRs. Three recent systematic reviews have revealed 22 unique studies evaluating microwave irradiation, heat, chemical disinfectants, and UVGI for decontamination of N95 FFRs [12] [13] [14] . UVGI and vaporous hydrogen peroxide showed favourable evidence for germicidal effects without significant changes in mask performance; however, we were not able to find any publications evaluating these methods in surgical masks.
The lack of research on surgical masks may stem from assumptions that methods effective in N95 FFRs can be extrapolated to surgical masks, and some institutions are already applying the same decontamination methods to both [38] . Considering this systematic review demonstrates that mask types can perform differently after decontamination, and that surgical masks and N95
FFRs perform differently with aerosol challenges [21, 39], we cannot conclude that decontamination methods can be effectively or safely applied to all mask types. Furthermore, common components of surgical masks such as cellulose-based materials, are known to degrade vaporous hydrogen peroxide and reduce the efficacy of sterilization [40] . There is also limited data evaluating the effectiveness of any PPE decontamination intervention against SARS-CoV-2 [38, 41] , although more studies are underway. Independent research on surgical masks is therefore critical in order to inform clinicians, infection control experts, and public health administrators on how best to advise safe decontamination and reuse practices.
Our systematic review has several important strengths. To our knowledge, this is the first systematic review of decontamination interventions in surgical mask PPE and provides important information describing the nature of interventions and outcomes evaluated to date. Our review highlights the variability in study methods and outcome reporting. As a result, we identified the following core outcomes to consider when conducting research in this field, to encourage consistent methodology and transparent reporting: mask performance (FE, airflow resistance), decontamination effects (germicidal effects, in vivo infection rates), physical characteristics of decontaminated masks, adverse effects to mask users, and intervention feasibility. We also developed a systematic tool with which to assess risk of bias in this body of literature.
Our review also has limitations. We were unable to conduct any meta-analyses due to the paucity of studies and their heterogeneous methodologies and outcome assessments. Outcomes described this systematic review required summarizing study results from multiple experiments; we rationalized the selective reporting of results in our methods to encourage conservative interpretation of the findings. Given the rapidly evolving landscape of PPE literature during the SARS-CoV-2 pandemic, we plan to update this systematic review at regular intervals for new relevant evidence as it becomes available (i.e. living systematic review) [42] .
There is inadequate evidence on the safety or efficacy of any decontamination intervention for extended use or reuse of surgical masks in the clinical setting. Further research should therefore be conducted specifically in surgical masks, that include decontamination interventions demonstrating promise in N95 FFRs (e.g. UVGI, vaporized hydrogen peroxide). To ensure the safety of HCPs and all end users, the same rigorous standard of research should be applied to surgical masks as with N95 FFRs, given its much broader applications as PPE. We recommend that future studies consider applying core outcomes and test conditions that are in accordance with acceptable industry standards in their design, to enable transparency of reporting and comparisons of efficacy between interventions. 1.6 (+0.3), p<0.05 FE, filtration efficiency; NS, not statistically significant. a FE to testing agent used, expressed as a percentage. A higher percentage filtration efficiency indicates better mask performance. Results in study were presented as percentage particle penetration, and converted to filtration efficiency (FE % = 100 -particle penetration) for consistency of reporting in this systematic review. b Airflow resistance assessed the "breathability" of the mask at tidal breathing. A lower airflow resistance means better breathability. 