Disclaimer: The aim of these rapid reviews is to retrieve, appraise, summarize and update the available evidence on COVID-related health technology. The reviews have not been externally peer- reviewed; they should not replace individual clinical judgement and the sources cited should be checked. The views expressed represent the views of the authors and not necessarily those of their host institutions. The views are not a substitute for professional medical advice.

Copyright Claims: This review is an intellectual property of the authors and of the Institute of Clinical Epidemiology, National Institutes of Health-UP Manila and Asia-Pacific Center for Evidence Based Healthcare Inc.

BACKGROUND

In light of the current pandemic, there is a potential for shortage of N95 facepiece filtering respirator (FFR) for healthcare workers. N95 FFRs are capable of filtering at least 95% of airborne particles.1 They are usually meant for single use. However, there is now a dwindling stock of PPEs particularly N95 respirators. To conserve the supply of N95 respirators, WHO recommends wearing N95 mask by healthcare workers only when doing aerosol generating procedures. These include tracheal intubation, non-invasive ventilation, tracheostomy, cardiopulmonary resuscitation, manual ventilation before intubation, bronchoscopy.2 US CDC allows the reuse of N95 during a pandemic. Reuse is defined by CDC as the practice of using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. N95 should be used by the same wearer and is only for “limited reuse.” 3

This rapid review explores the different methods in decontaminating N95 masks for reuse. “According to the Institute of Medicine, any method decontaminating

a disposable N95 FFR must remove the pathogen, be harmless to the user, and not compromise the integrity of the various parts of the respirator.”4 This review aims to find the available decontamination strategies that can sterilize and at the same time maintain the integrity of the mask after decontamination.

METHODS

See General Methods Section.

Articles were selected based on the following inclusion criteria:

•Population: General population / Health care workers / N95 mask exposed to any infectious agent

•Intervention: Any method of decontamination

•Outcomes: Incidence of Infection, sterilization efficiency, post-decontamination

•Study designs: randomized controlled trials (RCTs), non-randomized studies, observational studies (e.g. cohort, case-control, cross-sectional, case report, case series), laboratory based studies

RESULTS

Characteristics of Included Studies

We were not able to retrieve clinical studies on the said topic. Instead, we were able to find 13 laboratory based studies that tested various methods of decontamination on their ability to sterilize and to keep the integrity of the mask after decontamination. Unfortunately, none of these studies tested it on COVID-19 virus. Five studies assessed the impact of these methods in the integrity of the mask, four studies looked at the ability to decontaminate and one study analyzed both. Among the studies that tested its sterilization ability, 2 studies tested it using influenza virus (H1N1), another used influenza virus (A/H5N1), one on S. aureus, one used B. subtilis spores, one on different bacteriophages and one on G. stearothermophilus.

Among the studies found, the most studied methods of decontamination are ultraviolet germicidal irradiation (UVGI), microwave-generated steam, warm moist heat and hydrogen peroxide vapor. Regarding the use of ethylene oxide, hydrogen peroxide plasma, bleach and microwave irradiation, we were not able to find studies that look at their sterilization ability on N95 mask.

Effectiveness Outcomes

Ultraviolet Germicidal Irradiation

Many of the studies found tested the decontamination performance and post-decontamination filter performance of UVGI due to its practicality and viability in the hospital.

UVGI demonstrated a reduction of >4 log in both H1NI and H5N1 influenza virus when virus was aerosolized

or in droplets.5 However, its performance may go down to a reduction of log 1.25 if mask is soiled with mucus or sebum. Studies have shown that with after exposure to UVGI, the mean penetration percent remains below 5% even up to three times decontamination process which is still within acceptable standard. However, no studies established the effect of decontamination beyond three cycles. Initial resistance is also below 25mmH­20 which is still within NIOSH standard. They were conducted in 3 to

6 models of N95. The efficiency of UVGI which is primarily effective for surface decontamination may be hampered by the following: 1) hydrophilic material of facepieces or straps that may cause absorption of the virus away from the surface and 2) presence of shadows (shadowing effect) on ridges of facepieces and orientation of straps that indicate blocking of UV light on exposure.4

Nebraska Medicine, a network of hospitals in the United States of America, have devised a method to conserve N95 mask during the COVID-19 pandemic using UVGI. It makes use of UV light towers.6

Microwave Generated Steam

Another decontamination method widely studied is the microwave generated steam. It requires placing a mask on top of a perforated container filled with 50 ml of tap water and heated in a 1250 watt microwave oven at full power in 2 minutes. It was able to reduce by more than 4 log the viral load of both H1N1 and AH1N1 influenza virus. Both mean penetration and resistance is within acceptable range. However, in the same studies, it is not suitable for N95 models which have metal parts as it may melt in the process.5,7

Warm Moist Heat

Warm moist heat requires placing the mask on top of plastic rack and inside a container filled with water. This is then placed in an oven and heated for thirty minutes. It has a good decontamination performance and was able to reduce by >4 log the viral load of influenza with little changes in the mean penetration and resistance.5,7

In a study of Viscusi et al, UVGI, microwave generated steam and warm moist heat, does not change significantly the fit, comfort, or donning difficulty. This was done in 6 models of N95 mask. This was tested in 18 participants8. However, the results of Bergman et al showed that for a specific type of N95 mask (SN95-E) microwave generated steam and moist heat incubation caused partial separation of the inner foam nose cushion from the respirator.10

Chemical Sterilization

We were not able to find studies that assessed the decontamination performance of chemicals such as ethylene oxide, bleach, ethanol, isopropanol and liquid hydrogen peroxide. Their effect on mask integrity was done in three studies.9-11 Bleach, ethanol and isopropanol all increased

the mean penetration of the mask above the 5% limit.9 All do not leave a residue however bleach creates an odor that may be uncomfortable to the wearer.11,12

Hydrogen Peroxide Vapor

The United States of America (USA) Food and Drug Administration (FDA) has issued an Emergency Use Authorization (March 29, 2020) for the use of Batelle CCDS Critical Care Decontamination System™ in decontaminating N95 respirators and N95-equivalent respirators for reuse of healthcare workers. This system utilizes hydrogen peroxide vapor (HPV) for sterilization. The basis of its use is from a pilot study done by Batelle in 2016 which evaluated decontamination performance, respirator durability and respirator fit after numerous HPV cycles (up to 50 cycles). The results showed successful decontamination of the biologic indicator, G. stearothermophilus with measured hydrogen peroxide concentration below the permissible exposure limit. The aerosol collection efficiency was 99% and airflow resistance was 8 to 11 mm H2O. There were

no observed physical changes in the masks after 20 cycles, but strap degradation was noted after 30 cycles. Respirator fit was assessed using a manikin head form and results suggested fit was unaffected up to 20 HPV cycles. However, only 3M 1860 N95 respirators were used in this study so it is difficult to determine if results are reproducible with other types of N95 masks. Although respirator function was preserved, respirator fit cannot be properly assessed because human subject testing was not done.13 A study in 2020 evaluated the viricidal activity of HPV on 3M 1870 N95 respirators inoculated with aerosolized bacteriophages. Complete eradication of phages was noted after one cycle with no physical observable deformities. The respirator fit and function were not evaluated.14 The decontamination system authorized in the US did not undergo rigorous review as other FDA-approved devices but was issued an EUA due to no adequate, approved, available alternatives and with the belief from available evidence that HPV decontamination may be an effective way of protecting healthcare workers from pathogenic airborne particles.

Duke University has also begun decontaminating used N95 masks in their Regional Biocontainment Laboratory using hydrogen peroxide vapor (HPV). Their findings on performance and physical degradation as well as decontamination were consistent with the pilot study of 2016. In addition, the masks did not lose its fit or seal and had no noticeable odors when tested on 2-3 individuals. However, the process needs further validation.15

A

B

C

Figure 1. Decontamination method set-ups. (A) Microwave Generated Steam (B) Warm Moist Heat (C) Ultraviolet Germicidal Irradiation.

Image from Heimbuch BK., et al. A pandemic influenza preparedness study: use of energetic methods to decontaminate filtering facepiece respirators contaminated with H1N1 aerosols and droplets. Am J Infect Control, 2011; 39(1):e1-9.

Recommendations from Other Guidelines

The Centers for Disease Control (CDC) does not recommend the decontamination of FFRs for reuse as standard care. If this option needs to be considered due to FFR shortages, potential methods showing the most promise from limited studies include ultraviolet germicidal irradiation (UVGI), hydrogen peroxide vapor (HPV), and moist heat. Unless information is available from manufacturers that the specific respirator can be successfully decontaminated without compromising respirator performance, decontaminated FFRs should not be worn by healthcare workers performing or assisting in an aerosol-generating procedure. Precautionary measures should be taken when using decontaminated FFRs such as cleaning hands with soap and water before and after touching the FFR, using a pair of non-sterile gloves when donning the respirator and performing a seal check, inspecting the respirator for any defects or degradation of parts, and performing a user seal check. Respirators that does not pass visual inspection or user seal check should be discarded.19

CONCLUSION

Based on laboratory test done on N95, the following decontamination methods were shown to be effective in reducing either viral/bacterial load and still maintain the integrity of the mask: 1. Ultraviolet germicidal irradiation

2.Microwave generated steam 3. Warm moist heat 4. Hydrogen Peroxide Vapor. However, the effectiveness of these methods against SARS-CoV-2 is not known. Repetitive decontamination may also destroy the materials. Hence, precautionary measures need to be taken when handling decontaminated FFRs. None of the studies on N95 decontamination have extensively evaluated and met all the important criteria for decontamination methods which are as follows: the method must be effective against the target organism, not damage the respirator’s filtration, not affect the respirator’s fit and be safe for the person wearing the respirator. If any of the above measures are done, it should be tailored to the capacity of the hospital and its viability while taking the necessary precautions. Testing the mask for SARS-COV-2 after decontamination can validate it further.

Declaration of Conflict of Interest

No conflict of interest

REFERENCES

1.NPPTL [Internet]. NIOSH-Approved N95 Particulate Filtering Facepiece Respirators. 2020 [cited 2020 March 30]; Available from https://www.cdc.gov/niosh/npptl/topics/respirators/disp_part/ n95list1.html.

2.WHO, Rational use of personal protective equipment (PPE) for coronavirus disease (COVID-19): Interim Guidance. WHO: Geneva. 2020.

3.NIOSH [Internet]. Recommended Guidance for Extended Use and Limited Reuse of N95 Filtering Facepiece Respirators in Healthcare. 2020 March 27, 2020 [cited 2020 March 30]; Available from https://www.cdc.gov/niosh/topics/hcwcontrols/ recommendedguidanceextuse.html.

4.Mills D, Harnish DA, Lawrence C, Sandoval-Powers M, Heimbuch BK. Ultraviolet germicidal irradiation of influenza-contaminated N95 filtering facepiece respirators.Am J Infect Control.2018; 46(7):e49-e55.

5.Lore MB, Heimbuch BK, Brown TL, Wander JD, Hinrichs SH. Effectiveness of three decontamination treatments against influenza virus applied to filtering facepiece respirators. Ann Occup Hyg. 2012; 56(1):92-101.

6.Lowe JL, Paladino KD, Farke JD, Boulter K, Cawcutt K, Emodi M, et al. N95 filtering facepiece respirator ultraviolet germicidal irradiation (UVGI) process for decontamination and reuse. N. Medicine, Editor. 2020.

7.Heimbuch BK, Wallace WH, Kinney K, Lumley AE, Wu CY, Woo MH, et al. A pandemic influenza preparedness study: use of energetic methods to decontaminate filtering facepiece respirators contaminated with H1N1 aerosols and droplets. Am J Infect Control, 2011; 39(1):e1-9.

8.Viscusi DJ, Bergman MS, Novak DA, Faulkner KA, Palmiero A, Powell J, et al. Impact of three biological decontamination methods on filtering facepiece respirator fit, odor, comfort, and donning ease. J Occup Environ Hyg. 2011; 8(7):426-36.

9.Lin TH, Chen CC, Huang SH, Kuo CW, Lai CY, Lin WY. Filter quality of electret masks in filtering 14.6-594 nm aerosol particles: Effects of five decontamination methods. PLoS One. 2017; 12(10):e0186217.

10.Bergman MS, Viscusi DJ, Heimbuch BK, Wander JD, Sambol AR, Shaffer RE. Evaluation of Multiple (3-Cycle) Decontamination Processing for Filtering Facepiece Respirators. J Eng Fiber Fabr. 2010; 5(4):11.

11.Viscusi DJ, Bergman MS, Eimer BC, Shaffer RE. Evaluation of five decontamination methods for filtering facepiece respirators. Ann Occup Hyg, 2009; 53(8):815-27.

12.Salter WB, Kinney K, Wallace WH, Lumley AE, Heimbuch BK, Wander JD. Analysis of residual chemicals on filtering facepiece respirators after decontamination. J Occup Environ Hyg. 2010; 7(8):437-45.

13.Batelle Final Report for Bioquell HPV Decontamination for Reuse of N95 Respirators. F.C. Officers, Editor. Columbus, Ohio. 2016.

14.Kenney P, Chan BK, Kortright K, Cintron M, Havill N, Russi M, et al. Hydrogen Peroxide Vapor sterilization of N95 respirators for reuse. medRxiv. 2020.

15.Schwartz A, Stiegel M, Greeson N, et al. Decontamination and Reuse of N95 Respirators with Hydrogen Peroxide Vapor to Address Worldwide Personal Protective Equipment Shortages During the SARS-CoV-2 (COVID-19) Pandemic. Duke University. 2020.

16.Lin TH, Tang FC, Hung PC, Hua ZC, Lai CY. Relative survival of Bacillus subtilis spores loaded on filtering facepiece respirators after five decontamination methods. Indoor Air. 2018.

17.Lindsley WG, Martin SB Jr, Thewlis RE, Sarkisian K, Nwoko JO, Mead KR, et al. Effects of Ultraviolet Germicidal Irradiation (UVGI) on N95 Respirator Filtration Performance and Structural Integrity. J Occup Environ Hyg. 2015; 12(8):509-17.

18.Heimbuch BK, Kinney K, Lumley AE, Harnish DA, Bergman M, Wander JD. Cleaning of filtering facepiece respirators contaminated with mucin and Staphylococcus aureus. Am J Infect Control. 2014; 42(3):265-70.

19.Center for Disease Control and Prevention [Internet].Decontamination and Reuse of Filtering Facepiece Respirators using Contingency and Crisis Capacity Strategies. 2020 [cited 2020 April 02]. Available from https://www.cdc.gov/coronavirus/2019-ncov/hcp/ppe-strategy/ decontamination-reuse-respirators.html

Appendix 2. Literature search

Database

Search strategy / search terms

Medline ((((“Decontamination”[Mesh]) OR “Sterilization”[Mesh])) OR (Decontamination) OR (Sterilization)) AND ((N95) OR (N95 mask) OR (N95 respirator))

Date and time	Results
of search	Yield	Eligible
March 29, 2020	25	10