ABSTRACT

Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = -0.21 (95% CI, -0.34 to -0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

Keywords: Antiviral agents; COVID-19; SARS-CoV-2; Masks.

RESUMO

Objetivo: Avaliar a eficácia do uso de máscaras na prevenção da infecção por COVID-19. Métodos: Revisão sistemática e meta-análise de estudos de coorte e caso-controle, considerando o melhor nível de evidência disponível. Bancos de dados eletrônicos (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov) foram pesquisados para identificar estudos que avaliassem a eficácia do uso de máscaras em comparação com ausência de seu uso durante a pandemia de COVID-19. O risco de viés e a qualidade da evidência foram avaliados usando a ferramenta Cochrane risk of bias e Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Dos 1.028 estudos identificados, 9 preencheram os critérios de inclusão (2 estudos de coorte e 7 estudos de caso-controle) e foram incluídos na análise. A meta-análise usando apenas estudos de coorte mostrou diferenças estatisticamente significativas: o uso de máscara de tecido diminuiu 21% [(risk difference = −0,21 (IC 95%: −0,34 a −0,07); I2 = 0%; p = 0,002] o risco de infecção por COVID-19, mas a qualidade da evidência foi baixa. Em relação aos estudos caso-controle, o uso de máscara cirúrgica reduziu a chance de infecção por COVID-19 [OR = 0,51 (IC 95%: 0,37-0,70); I2 = 47%; p = 0,0001], assim como o uso de máscara respiratória N95 [OR = 0,31 (IC 95%: 0,20-0,49); I2 = 0%; p = 0,00001], ambos com baixa qualidade de evidência. Conclusões: Nesta revisão sistemática com meta-análise, demonstramos a eficácia do uso de máscaras na prevenção da infecção por SARS-CoV-2 independentemente do tipo de máscara (máscara cirúrgica descartável, máscaras comuns, incluindo máscaras de tecido, ou respiradores N95), embora os estudos avaliados apresentassem evidências de baixa qualidade e vieses importantes.

Palavras-chave: Agentes antivirais; COVID 19; SARS-CoV-2; Máscaras.

 
INTRODUCTION
 
After the first case of COVID-19 in November of 2019, the pandemic has widely spread worldwide, causing numerous deaths from SARS-CoV-2-related ARDS. The transmission of respiratory viruses such as SARS-CoV-2 can occur through saliva droplets, person-to-person contacts, or contaminated surfaces,(1,2) and it can be avoided by barriers and social distancing protection.
 
At the beginning of the pandemic, there was a sudden and marked increase in the consumption of personal protective equipment (PPE), which, in association with social distancing, were the only methods to prevent the spread of the virus before vaccine availability. With the advent of vaccines, there was a marked reduction in infection and mortality rates, but those were still high. Nowadays, the use of PPE is adaptive considering the recommendations of local health agencies and COVID-19 incidence rates. The WHO(3) and the U.S. Centers for Disease Control and Prevention(4) recognize that wearing well-fitted masks and maintaining social distancing, such as avoiding crowded or closed-contact settings, as well as cleaning hands regularly and covering sneezes and coughs, reduce COVID-19 transmission. Masks can be used to protect healthy people or to prevent onward transmission. On the other hand, there is a concern related to the real effectiveness of the different types of masks in reducing the transmission of COVID-19. Commercially, there are three types of masks commonly sold in order to protect against aerial contamination: cloth face masks, worn by the general population; medical face masks (surgical face masks), worn by health care agents; and N95 respirators or equivalents, worn by health care professionals in the presence of aerosol contaminants.
 
Previous systematic reviews in the literature on this topic(5-7) did not take into consideration the relationship between the type of respiratory viruses and their respiratory infection rate, and this directly impacted on the results. Moreover, those studies had different study designs, creating bias and reducing the quality and reliability of the data obtained. To improve the information regarding the effectiveness of masks used during the COVID-19 pandemic, this systematic review was carried out with a selection of studies published during the COVID-19 pandemic, which were stratified according to the types of masks (cloth masks, surgical masks, and N95 respirators) used around the world, as well as the types of study design.
 
METHODS
 
This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.(8)
 
Eligibility criteria
 
The protocol of this study was based on the PICO methodology (Patients of interest, Intervention to be studied, Comparison of intervention, and Outcome of interest). Therefore, the PICO framework in the present study was as follows: Patients: adults at risk of being infected with SARS-CoV-2; Intervention: use of face masks; Comparison: individuals who did not wear face masks; and Outcome: COVID-19 infection. Observational (cohort or case-control) studies were included in this study, and no restrictions regarding the date of publication, language, or full-text availability were imposed.
 
Information sources and search strategy
 
Two authors developed a search strategy that was revised and approved by the team, selected information sources, and systematically searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, as well as gray literature. The main search strategy used was the following: “(mask OR masks OR N95 OR (Respiratory Protective Devices OR Respiratory Protective Device) OR face shield) AND (COVID OR COV OR CORONAVIRUS OR SARS) AND (random*) OR therapy/broad[filter] OR comparative study OR comparative studies).” The search strategy included studies published by November 1, 2022.
 
Study selection
 
Two independent researchers selected and extracted the data from the studies included. First, the studies were selected based on their titles and abstracts. Second, full texts were evaluated to be included or excluded, and disagreements were resolved by consensus or following a discussion with a third researcher.
 
Data collection and investigated outcomes
 
Data regarding authorship, year of publication, patient description, interventions (wearing masks or control), absolute numbers of each outcome, and follow-up period were extracted from the studies.
 
Risk of bias and quality of evidence
 
The risk of bias for cohort and case-control studies was assessed using the current tool recommended by the Cochrane Collaboration to estimate the effectiveness and safety of nonrandomized interventional studies, designated Risk of Bias in Non-randomized Studies of Interventions.(9) This tool assesses seven domains of bias, classified by the time of occurrence, as were other fundamental elements, and are expressed as low risk, moderate risk, serious risk, critical risk, or no information.
 
The assessment of the risk of bias was conducted by two independent reviewers, and, in case of disagreement, a third reviewer deliberated on the assessment. The quality of evidence was extrapolated from the risk of bias and was described by using the Grading of Recommendations Assessment, Development and Evaluation terminology(10,11) as very low, low, moderate, or high; the quality of evidence was described by the GRADEpro Guideline Development Tool (McMaster University, Hamilton, ON, Canada) for meta-analyses.
 
Synthesis of results and statistical analysis
 
Categorical outcomes were expressed by group (wearing masks or control): number of events and calculated risk in percentage (by dividing the number of events by the total number of individuals in each group) for cohort and case-control studies. The effectiveness of wearing a face mask for preventing transmission of COVID-19 respiratory infections in community settings was assessed using ORs and their respective 95% CIs for case-control studies. For cohort studies, the effects of meta-analyses were reported as risk differences (RDs) or ORs and corresponding 95% CIs. The use of RDs shows the absolute effect size in the meta-analysis when compared with the relative risk or the OR, and this technique can be used when the binary outcome is zero in both study arms. We used the fixed-effect or the random-effect model in the meta-analysis to evaluate the effect of intervention vs. control on the outcome when these data were available in at least two studies. The heterogeneity of effects among studies was quantified using the I2 statistic (I2 > 50% indicating high heterogeneity). For the meta-analysis, we used the Review Manager software, version 5.4 (RevMan 5; Cochrane Collaboration, Oxford, United Kingdom). (12) Results were expressed using a methodological (observational cohort study) design.
 
RESULTS
 
A flow diagram of the literature search and related screening process is shown in Figure 1. The search strategy identified 1,367 studies, and, after screening titles and abstracts, we identified 57 potentially eligible citations. After applying inclusion and exclusion criteria, we retrieved 18 citations for full-text analysis, and 9 studies(13-21)
were included in this systematic review, 2 of those being cohort studies(13,14) and 7 being case-control studies.(15-21) The list of excluded studies and the reasons for their exclusion are available in the supplementary material. The characteristics of the studies included are described in Table 1. The risk of bias and the quality of evidence are described in Tables 2 and 3, respectively. No publication bias was identified.
 

 
A total of 2,803 participants (192 in the cohort studies and 2,611 in the case-control studies) were included in the analysis (wearing a mask or not) in terms of effectiveness to decrease the indices of COVID-19 infection.
 
Regarding the risk of bias, all of the studies included showed high or critical biases due to confusion, selection of participants, or missed dates. Overall, the studies were considered to have a high risk of bias (Table 2): a serious risk in 5 studies and a moderate risk in 3 studies.
 

 
The cohort studies evaluated 192 participants on the effectiveness of wearing a mask (disposable surgical masks or common masks, including cloth masks) in preventing COVID-19 infection. The wearing of masks was associated with an important reduction (by 21%) in the risk of COVID-19 infection [RD = −0.21 (95% CI, −0.34 to −0.07); I2 = 0%; p = 0.002], which indicated that it was necessary that 5 participants should wear a mask to avoid 1 COVID-19 case, with a low quality of evidence (Figure 2).
 

 
Six case-control studies included 729 subjects in the intervention group and 1,074 in the control group. The meta-analysis showed that the chance of contracting COVID-19 infection was 0.49 times lower in those who wore masks [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%, p = 0.0001] when compared with the control group, with a low quality of evidence (Figure 3). The specific use of the N95 respirator masks was assessed in 4 case-control studies, which included 414 participants in the N95 mask group and 395 in the control group. The N95 mask group showed to have a 0.69 lower chance of acquiring COVID-19 infection in comparison with those who did not wear a mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%, p = 0.00001], with a low quality of evidence (Figure 3).
 

 
Summary of evidence
 

• The use of masks (disposable surgical masks or common masks, including cloth masks) caused a reduction of 21% in the risk of COVID-19 infection [RD = −0.21 (95% CI, −0.34 to −0.07); I2 = 0%, p = 0.002] in the cohort stu-dies included, with a low certainty of evidence


• The use of surgical masks decreased the chance of COVID-19 infection by 49% [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%, p = 0.00001] in the case-control studies included, with a low certainty of evidence


• The use of N95 respirator masks demonstrated a significant protective effect in decreasing (by 69%) the chance of COVID-19 infection [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001] in the case-control studies included, with a low certainty of evidence

 
DISCUSSION
 
Our systematic review demonstrates a reduction in the risk of COVID-19 infection. By evaluating different subgroups of study designs (cohort studies whose intervention was the use of disposable surgical masks, common masks, including cloth masks, or N95 respirators; and case-control studies whose intervention was wearing surgical masks or N95 respirator masks), we obtained a relevant reduction in the risk of COVID-19 infection, regardless of the type of mask, but the certainty of evidence was low.
 
Comparing our results with those of other systematic reviews, we can claim that wearing masks can contribute to reducing COVID-19 infection. The previous literature studied the effect of wearing masks in different scenarios, different types of infectious aerosols, and different rates of infection. It is important to promote reliable knowledge and education to society regarding the use of facial masks as an instrument of individual protection. Japan is one of the countries that culturally educated its population to wear masks to protect others when they present respiratory symptoms. Nevertheless, this is not the only instruction that we can provide to protect against COVID-19 infection. We need to remember to maintain social distancing, hand hygiene, and other essential measures.
 
Xu et al.(22) have shown that indoor environments can contain high rates of aerosol dispersants, which may promote high rates of viral transmission; however, when wearing an N95 respirator or a surgical mask, the level of aerosols can be reduced significantly. Likewise, Araújo et al.(5) demonstrated that wearing face masks in a community scenario can significantly decrease viral infections. Moreover, surgical masks offer higher protection when compared with cloth masks. On the other hand, to achieve a significant reduction in COVID-19 transmission, more than half of the population needs to be wearing masks. Therefore, the rate of infection transmission is important to be considered by public health recommendations regarding the use of masks. Nowadays, when we observe a new and more transmissible SARS-CoV-2 strain, a low rate of vaccination, and/or no use of facial masks, we may await more critical outcomes, such as increases in the number of hospitalizations and deaths again.
 
When we evaluated the use of masks without stratifying the specific type of mask or study design, there was a 57% reduction in the chance of COVID-19 infection (Figure 3). Regarding the comparison between surgical masks and N95 respirators, regardless of the study design, we found a 49% and 69% reduction in the chance of COVID-19 infection, respectively The difference in protection between surgical masks and N95 respirators is due to the difference in the permeability of the material used in their manufacture, because the material used in N95 respirator masks is less impermeable than that used in surgical masks, offering greater protection. However, there are biases, such as time of use, training for use, and number of times of exposure to contaminants and to places with a higher chance of contamination, that are determining factors in greater or lesser protection when using PPE.
 
This systematic review had some limitations: the first and major limitation is the huge variability in viral incidence (i.e., lack of preliminary estimates of the basic reproduction number [R0] of SARS-CoV-2); the assessment of the effectiveness of wearing a mask can directly correlate to adherence, time of use, type of location of exposure, incidence of COVID-19 infection at the study site, type of mask, social distancing, and other factors. In addition, the studies included in this review were performed during the COVID-19 pandemic; however, the R0 of each study was probably different, a fact that can cause largely different results. Moreover, most of the studies included were considered to have a serious risk of bias and a low certainty of evidence.
 
Because of the difficulty in conducting good-quality randomized controlled trials during a pandemic that has spread around the world rapidly, we needed to work with the best evidence available.
 
FINAL CONSIDERATIONS
 
The use of masks showed effectiveness in the prevention of SARS-CoV-2, regardless of the mask type (disposable surgical masks, common masks, including cloth masks, or N95 respirators). However, the certainty of evidence was low.
 
AUTHOR CONTRIBUTIONS
 
IF, AS, HAB, AN, ST, and WMB: study concept and design. IF and AS: data collection. IF, AS, and WB: statistical analyses and interpretation of data. WMB and SET: drafting of the manuscript. IF, AS, SET, HAB, AN, ST, and WMB: critical review and approval of the final version of the manuscript.
 
CONFLICTS OF INTEREST
 
None declared.
 
REFERENCES
 
1.Canini L, Andréoletti L, Ferrari P, D’Angelo R, Blanchon T, Lemaitre M, et al. Surgical mask to prevent influenza transmission in households: a cluster randomized trial. PLoS One. 2010;5(11):e13998. https://doi.org/10.1371/journal.pone.0013998
2.Cowling BJ, Zhou Y, Ip DK, Leung GM, Aiello AE. Face masks to prevent transmission of influenza virus: a systematic review. Epidemiol Infect. 2010;138(4):449-456. https://doi.org/10.1017/S0950268809991658
3.World Health Organization [homepage on the Internet]. Geneva: World Health Organization; c2020 [cited 2020 Apr 8]. Coronavirus disease (COVID-19) advice for the public: When and how to use masks. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/when-and-how-to-use-masks
4.Centers for Disease Control and Prevention (CDC) [homepage on the Internet]. Atlanta: CDC; c2019 [cited 2020 Apr 8]. Recommendation regarding the use of cloth face coverings, especially in areas of significant community-based transmission. Available: https://www.cdc.gov/coronavirus/2019-ncov/prevent- getting- sick/cloth-facecover html
5.Araujo CM, Guariza-Filho O, Gonçalves FM, Basso IB, Schroder AGD, Cavalcante-Leão BL, et al. Front lines of the COVID-19 pandemic: what is the effectiveness of using personal protective equipment in health service environments?-a systematic review. Int Arch Occup Environ Health. 2022;95(1):7-24. https://doi.org/10.1007/s00420-021-01775-y
6.Coclite D, Napoletano A, Gianola S, Del Monaco A, D’Angelo D, Fauci A, et al. Face Mask Use in the Community for Reducing the Spread of COVID-19: A Systematic Review. Front Med (Lausanne). 2021;7:594269. https://doi.org/10.3389/fmed.2020.594269
7.Chou R, Dana T, Jungbauer R, Weeks C, McDonagh MS. Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings : A Living Rapid Review. Ann Intern Med. 2020;173(7):542-555. https://doi.org/10.7326/M20-3213
8.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71
9.Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https://doi.org/10.1136/bmj.i4919
10.GRADE Working Group [homepage on the Internet]. c2021 [cited 2021 Aug 1]. GRADE. Available from: https://www.gradeworkinggroup.org/
11.GRADEpro GDT [homepage on the Internet]. Hamilton, Canada: McMaster University and Evidence Prime; c2021. GRADEpro Guideline Development Tool [Software]. Available from: https://www.gradepro.org/
12.Review Manager (RevMan) [Computer Program]. version 5.4. The Cochrane Collaboration; 2020.
13.Chen Y, Tong X, Wang J, Huang W, Yin S, Huang R, et al. High SARS-CoV-2 antibody prevalence among healthcare workers exposed to COVID-19 patients. J Infect. 2020;81(3):420-426. https://doi.org/10.1016/j.jinf.2020.05.067
14.Wang Y, Tian H, Zhang L, Zhang M, Guo D, Wu W, et al. Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Glob Health. 2020;5(5):e002794. https://doi.org/10.1136/bmjgh-2020-002794
15.Andrejko KL, Pry JM, Myers JF, Fukui N, DeGuzman JL, Openshaw J, et al. Effectiveness of Face Mask or Respirator Use in Indoor Public Settings for Prevention of SARS-CoV-2 Infection - California, February-December 2021. MMWR Morb Mortal Wkly Rep. 2022;71(6):212-216. https://doi.org/10.15585/mmwr.mm7106e1
16.Doung-Ngern P, Suphanchaimat R, Panjangampatthana A, Janekrongtham C, Ruampoom D, Daochaeng N, et al. Case-Control Study of Use of Personal Protective Measures and Risk for SARS-CoV 2 Infection, Thailand. Emerg Infect Dis. 2020;26(11):2607-2616. https://doi.org/10.3201/eid2611.203003
17.Guo X, Wang J, Hu D, Wu L, Gu L, Wang Y. Survey of COVID-19 Disease Among Orthopaedic Surgeons in Wuhan, People’s Republic of China. J Bone Joint Surg Am. 2020;102(10):847-854. https://doi.org/10.2106/JBJS.20.00417
18.Heinzerling A, Stuckey MJ, Scheuer T, Xu K, Perkins KM, Resseger H, 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(15):472-476. https://doi.org/10.15585/mmwr.mm6915e5
19.Khalil MM, Alam MM, Arefin MK, Chowdhury MR, Huq MR, Chowdhury JA, et al. Role of Personal Protective Measures in Prevention of COVID-19 Spread Among Physicians in Bangladesh: a Multicenter Cross-Sectional Comparative Study. SN Compr Clin Med. 2020;2(10):1733-1739. https://doi.org/10.1007/s42399-020-00471-1
20.Rebmann T, Loux TM, Arnold LD, Charney R, Horton D, Gomel A. SARS-CoV-2 Transmission to Masked and Unmasked Close Contacts of University Students with COVID-19 - St. Louis, Missouri, January-May 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1245-1248. https://doi.org/10.15585/mmwr.mm7036a3
21.Wang X, Pan Z, Cheng Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect. 2020;105(1):104-105. https://doi.org/10.1016/j.jhin.2020.02.021
22.Xu H, Gan Y, Zheng D, Wu B, Zhu X, Xu C, et al. Relationship Between COVID-19 Infec-tion and Risk Perception, Knowledge, Attitude, and Four Nonpharmaceutical Inter-ventions During the Late Period of the COVID-19 Epidemic in China: Online Cross-Sectional Survey of 8158 Adults. J Med Internet Res. 2020;22(11):e21372. https://doi.org/10.2196/21372