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Physio-metabolic and clinical consequences of wearing face masks -Systematic review with meta-analysis and comprehensive evaluation

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Abstract and Figures

Background: As face masks are a mandatory public health intervention during the COVID-19 pandemic, adverse effects require substantiated investigation. Methods: A systematic review of 2168 studies yielded 54 publications for synthesis and 37 studies for meta-analysis (on n=8641, m=2482, f=6159, age=34.8±12.5). The median trial duration was only 18 min (IQR=50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes. Results: We found significant effects in both medical masks with a greater impact regarding the N95. These effects included decreased SpO2 (overall SMD=-0.24, 95%CI=-0.38 to -0.11, p=0.0004) and minute ventilation (SMD=-0.72, 95%CI=-0.99 to -0.46, p<0.00001), simultaneously increased blood-CO2 (SMD=+0.64, 95%CI=0.31–0.96, p=0.0001), heart rate (N95: SMD=+0.22, 95%CI=0.03–0.41, p=0.02), systolic blood pressure (surgical: SMD=+0.21, 95%CI=0.03–0.39, p=0.02), skin temperature (overall SMD=+0.80 95%CI 0.23–1.38, p=0.006) and humidity (SMD +2.24, 95%CI=1.32–3.17, p<0.00001). Effects on exertion (overall SMD=+0.9, surgical=+0.63, N95=+1.19), discomfort (SMD=+1.16), dyspnoea (SMD=+1.46), heat (SMD=+0.70) and humidity (SMD=+0.9) were significant in 373 cases with a robust relationship to mask wearing (p<0.006 to p<0.00001). Pooled symptom prevalence was significant in users (n=8128) for: headache (62%, p<0.00001), acne (38%, p<0.00001), skin irritation (36%, p<0.00001), dyspnoea (33%, p<0.00001), heat (26%, p<0.00001), itching (26%, p<0.00001), voice disorder (23%, p<0.03) and dizziness (5%, p=0.01). Discussion: Masks interfered with O2-uptake and CO2-release and compromised respiratory compensation. Though evaluated wearing durations do not represent daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES). MIES can have long-term clinical consequences, especially for vulnerable groups. Conclusion: Face mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions.
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Physio-metabolic and clinical consequences of
wearing face masks -Systematic review with meta-
analysis and comprehensive evaluation
Kai Kisielinski ( kaikisielinski@yahoo.de )
Orthopaedic and Trauma surgery, Clinical medicine, Private practice, 40212 Düsseldorf, Germany
https://orcid.org/0000-0002-2612-6256
Oliver Hirsch
Department of Psychology, FOM University of Applied Sciences, 57078 Siegen, Germany
Susanne Wagner
Veterinary medicine, Wagner MSL Management, 15831 Mahlow, Germany
Barbara Wojtasik
Department of Genetics and Biosystematics, Faculty of Biology, University of Gdańsk, 80-308, Gdansk,
Poland
Stefan Funken
Internal medicine, Clinical medicine, Private practice, 47447 Moers, Germany
Bernd Klosterhalfen
Institute of Pathology, Dueren Hospital, 52351 Dueren, Germany
Soumen Kanti Manna
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata 700064, India
Andreas Prescher
Institute of Molecular and Cellular Anatomy (MOCA), RWTH Aachen University, 52074 Aachen, Germany
Pritam Sukul ( pritam.sukul@uni-rostock.de )
Rostock Medical Breath Research Analytics and Technologies (ROMBAT), Dept. of Anesthesiology and
Intensive Care, University Medicine Rostock, 18057 Rostock, Germany https://orcid.org/0000-0001-
5114-1776
Andreas Sönnichsen
Internal medicine, Clinical medicine, Private practice, Gesundheit für Österreich e.V. (Health for Austria),
1030 Vienna, Austria
Systematic Review
Keywords: face masks, N95 face mask, surgical mask, risk, adverse effects, long-term adverse effects,
health risk assessment, hypercapnia, hypoxia, MIES syndrome
DOI: https://doi.org/10.21203/rs.3.rs-2394501/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License. 
Read Full License
Consequences of wearing face masks
Physio-metabolic and clinical consequences of wearing face masks
-Systematic review with meta-analysis and comprehensive
evaluation
Kai Kisielinski1,*, Oliver Hirsch2, Susanne Wagner3, Barbara Wojtasik4, Stefan Funken5, Bernd
Klosterhalfen6, Soumen Kanti Manna7, Andreas Prescher8, Pritam Sukul9,*, Andreas Sönnichsen10
1,*Orthopaedic and Trauma surgery, Clinical medicine, Private practice, 40212 Düsseldorf, Germany
2Department of Psychology, FOM University of Applied Sciences, 57078 Siegen, Germany
3Veterinary medicine, Wagner MSL Management, 15831 Mahlow, Germany
4Department of Genetics and Biosystematics, Faculty of Biology, University of Gdańsk, 80-308, Gdansk, Poland
5Internal medicine, Clinical medicine, Private practice, 47447 Moers, Germany
6Institute of Pathology, Dueren Hospital, 52351 Dueren, Germany
7Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata 700064, India
8Institute of Molecular and Cellular Anatomy (MOCA), RWTH Aachen University, 52074 Aachen, Germany
9,*Rostock Medical Breath Research Analytics and Technologies (ROMBAT), Dept. of Anesthesiology and Intensive Care, University Medicine
Rostock, 18057 Rostock, Germany
10Internal medicine, Clinical medicine, Private practice, Gesundheit für Österreich e.V. (Health for Austria), 1030 Vienna, Austria
*Corresponding authors: kaikisielinski@yahoo.de & pritam.sukul@uni-rostock.de
Abstract
Background: As face masks are a mandatory public health intervention during the COVID-19
pandemic, adverse effects require substantiated investigation.
Methods: A systematic review of 2168 studies yielded 54 publications for synthesis and 37 studies
for meta-analysis (on n=8641, m=2482, f=6159, age=34.8±12.5). The median trial duration was
only 18 min (IQR=50) for our comprehensive evaluation of mask induced physio-metabolic and
clinical outcomes.
Results: We found significant effects in both medical masks with a greater impact regarding the
N95. These effects included decreased SpO2 (overall SMD=-0.24, 95%CI=-0.38 to -0.11, p=0.0004)
and minute ventilation (SMD=-0.72, 95%CI=-0.99 to -0.46, p<0.00001), simultaneously increased
blood-CO2 (SMD=+0.64, 95%CI=0.31–0.96, p=0.0001), heart rate (N95: SMD=+0.22,
95%CI=0.03–0.41, p=0.02), systolic blood pressure (surgical: SMD=+0.21, 95%CI=0.03–0.39,
p=0.02), skin temperature (overall SMD=+0.80 95%CI 0.23–1.38, p=0.006) and humidity (SMD
+2.24, 95%CI=1.32–3.17, p<0.00001). Effects on exertion (overall SMD=+0.9, surgical=+0.63,
N95=+1.19), discomfort (SMD=+1.16), dyspnoea (SMD=+1.46), heat (SMD=+0.70) and humidity
(SMD=+0.9) were significant in 373 cases with a robust relationship to mask wearing (p<0.006 to
p<0.00001). Pooled symptom prevalence was significant in users (n=8128) for: headache (62%,
p<0.00001), acne (38%, p<0.00001), skin irritation (36%, p<0.00001), dyspnoea (33%, p<0.00001),
heat (26%, p<0.00001), itching (26%, p<0.00001), voice disorder (23%, p<0.03) and dizziness (5%,
p=0.01).
Discussion: Masks interfered with O2-uptake and CO2-release and compromised respiratory
compensation. Though evaluated wearing durations do not represent daily/prolonged use, outcomes
independently validate mask-induced exhaustion-syndrome (MIES). MIES can have long-term
clinical consequences, especially for vulnerable groups.
Conclusion: Face mask side-effects must be assessed (risk-benefit) against the available evidence
of their effectiveness against viral transmissions.
Consequences of wearing face masks
Introduction
The use of face masks has been restricted to professionals for decades. In the health-care setting,
masks constituted a mandatory self-protective and third-party protective measure for medical
personnel prior to COVID-19 pandemic and there is no doubt about the efficacy of masks in
reducing transmission of pathogens, especially bacteria. In 2020, many scientists and leaders started
to believe that the use of masks could also provide protection against viral transmission, although
evidence for the effectiveness of this measure was only weak 1. In the meantime, a large number of
publications on this topic cannot be overlooked 2,3.
During the 2019 SARS-CoV-2 outbreak face masks were deployed as a mandatory public health
measure for the general population in many countries around the world, making them one of the
most important universal life-style attributes that directly affects how we breathe. As with any other
preventive measure and/or intervention, masks also have specific advantages and disadvantages.
While certain properties may have justified their invention and application in the past, e.g. retention
of bacteria during surgical wound care and operations, at present the question needs to be addressed
as to the long-term effects widespread mask wearing may have on normal breathing. It is
noteworthy that the compulsory wearing of masks for the entire population provided good research
conditions and consequently numerous publications dealing with the adverse effects of mask
wearing 4–11. Various volatile metabolites are produced from in vivo biochemical and metabolic
pathways and their concentrations in exhaled breath provide immediate physiological 12,13,
metabolic 14,15 and pathological 16,17 magnitudes with the possibility of monitoring various processes
and interventions including therapies 18,19. A recent observational study reported continuous
respiratory and haemodynamic changes along with corresponding alteration in exhaled volatile
metabolites (viz. potentially originate at the cellular/organ levels and via microbial metabolic
processes) and has raised significant concerns upon the immediate, progressive, transient and long-
term side-effects of FFP2/N95 and surgical masks in adults (aged between 20 – 80 years) at rest 20.
Previously, based on other numerous publications major concerns were raised in a large-scale
scoping review 8. Furthermore, this recent scoping review on mask driven adverse effects and health
risks has summoned for a systematic review.
Though some important systematic reviews regarding masks and their effects already exist 21–24,
they are predominantly restricted to healthy and sportive individuals 21,23. Due to the exclusion of
children, pregnant women and diseased patients from these evaluations and conclusions 22,25, the
reviews do not provide sufficient evidence that masks can be employed in the general population as
safe protective measures. Moreover, the application of fixed statistical models 21, use of narratives
rather than quantitative analysis and statistics (despite claiming to be systematic) 26, focus only on
health care workers and their complaints 25, as well as comparing the different mask types without
any baseline/control group 25 were ubiquitous limitations of those studies. Physiological systematic
reviews based purely on physiological effects of masks limit data interpretations to normal physio-
metabolic fluctuations i.e. beyond the domain of pathophysiological compensatory mechanisms
(especially in the elderly and those with diminished compensatory reserves) and/or acute/chronic
subliminal changes in the human microbiome 22,24. Similarly, other manuscripts do not address
subjective parameters, prevalence of symptoms and discomfort during mask use and concomitant
physical changes such as heat and temperature in detail 21,23. Therefore, the systematic reviews
available to date neither address possible symptoms of mask use for the general population nor their
exact prevalence. In addition, the transferability of the outcomes of said systematic reviews to the
general population is very limited and they do not fulfil the actual requirements of clinical and
inclusive evaluation, especially from the views and perspective of physicians and clinicians.
Including young, old, healthy and ill people for the systematic analysis of physiological, metabolic
and clinical data could complete the possible comprehensive impact of mask-wearing on the general
Consequences of wearing face masks
population. In contrast to the above-indicated studies, our systematic review is aimed to quantify the
biochemical/metabolic, physical, physiological changes along with the appearance of subjective and
clinical symptoms in face mask users and analyse them form a clinician´s and physician´s holistic
perspective.
Materials & Methods
Registration
This meta-analysis was registered with the international prospective register of systematic reviews
(PROSPERO) under the record CRD42021256694 at the National Institute for Health Research
(NIHR) and performed in accordance with the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) Statement 27.
Inclusion and exclusion criteria
The aim was to study adverse effects of face masks on metabolic, physiological, physical,
psychological and individualised parameters. The use of cloth masks, surgical masks and N95/FFP-
2 masks were the intervention of interest. Humans of all ages and genders, who were evaluated in
controlled intervention studies and observational studies have been included in our comprehensive
evaluation. Case reports, narrative reviews, case series and expert opinions were excluded. The
main outcomes considered were peripheral oxygen saturation (SpO2), carbon dioxide levels in
blood, temperature, humidity, heart rate, respiratory rate, tidal volume and minute ventilation, blood
pressure, exertion, dyspnoea, discomfort, headache, skin changes, itching, psychological stress and
symptoms during the use of face masks.
Literature retrieval strategy
First, a comprehensive search term was developed. Then, PubMed, Embase and Cochrane Library
databases were searched. The search was performed until 31st December 2021. There were no
restrictions in publication date. Literature that was neither English nor German language was
excluded. Additionally, forward-looking data (e.g. available as preprint, but not published in a peer-
reviewed scientific journal at time of completing this meta-analysis) was considered for discussion,
but not included in the meta-analysis.
Literature screening and data extraction
Search terms were created according to the criteria defined in the PICO scheme 28. The specific
search terms were: (face mask* [tw], FFP1 [tw] FFP2 [tw], FFP3 [tw], N99 [tw], N97 [tw], N95
[tw], respiratory protective device* [tw], air-purifying respirator* [tw], surgical mask* [tw]) and
(risk* or adverse effect* [tw], adverse event* [tw], side effect* [tw], psycho* [tw], hypoxia [tw],
hypercapnia [tw], headache [tw], dead space [tw], safety [tw], carbon dioxide [tw]), not infants, not
neonatal, not newborn, not endoscopy, not CPAP, not intubate*, not propofol, not resuscitation, not
mechanical ventilation [tw], not foetus. The asterisk in the search algorithm here ‘*’ stands for the
extension of the spelling with different possible letter combinations (e.g. face mask* with *= s, or
*=ed, or *=ing). The abbreviation ‘[tw]’ stands for title word.
The retrieved titles and abstracts were then screened and assessed for predefined inclusion criteria
by at least three authors. Study design, methodology, interventions, primary and secondary
Consequences of wearing face masks
outcomes and language were evaluated using the web-based program Rayyan — a web and mobile
app for systematic reviews 29. Full texts of all potentially relevant articles were independently
assessed for inclusion by two authors. Full-text exclusions and reasons have been documented. Data
of included full texts were extracted: Author and year, type of study, aim of the study,
intervention/control, sample size, follow-up, outcomes, funding, setting/country, age, sex,
comorbidities, medications, functional status and cognitive status of participants, results, main
findings, and limitations. Descriptive data was extracted by one author and checked by a senior
author. If discrepancies occurred or authors disagreed, a senior author was involved in and a
consensus was found 30.
Risk of bias assessment of the included studies
The quality assessments were carried out using various tools, depending on the type of study. If
systematic reviews and meta-analyses were included, these were assessed using the AMSTAR-2
checklist 31. Interventional studies were examined using the manual “Assessment of the risk of bias
in clinical studies” from the Cochrane Collaboration (Cochrane RoB-2) 32. Observational studies
were checked with the CASP (Critical Appraisal Skills Program) using standardised forms 33.
Statistical analysis
A meta-analysis was carried out, if enough studies with the same research question were found
among the randomised, non-randomised controlled trials and observational studies. A subgroup
analysis was conducted, where possible, for different mask types (N95/surgical) and even compared
the mask types with each other (N95 vs surgical mask). The program "RevMan-5.4.1", which was
developed for Cochrane Reviews was used. As we anticipated a considerable between-study
heterogeneity -the random effects model was used to pool effect sizes 34. The results were
graphically depicted in forest plots. Subgroup analyses were performed and a Q test was calculated
to examine significant subgroup differences. Study heterogeneity was assessed using Cochrane´s Q
test, T2 according to DerSimonian / Laird 35, and I² according to Higgins / Thompson 36. Where
possible, a funnel plot was created to investigate publication bias. If this showed an abnormal result
and there were at least ten studies evaluating the same question, Egger´s test 37 was carried out.
For the analysis of metabolic and physiological changes all controlled intervention studies in which
measurements were taken during physical activity with face masks were included. We excluded
resting conditions since these are not representative for real life settings and pre-post studies to
ensure study-comparability. In addition, by excluding rest situations of the mostly healthy study
participants, our approach was able to represent the possible effects better in elderly and ill
individuals (e.g. with compromised compensation mechanisms), all of whom are a significant part
of the general population. This also helped to reduce heterogeneity (I2). Neither for the results of the
systolic blood pressure (SBP) nor the temperature did we follow this approach. Studies in which
measurements were taken during rest and moderate physical activity were included in the meta-
analysis of the physical outcome on SBP to obtain an evaluable number of studies and to ensure a
better comparability and lower heterogeneity (exclusion of heavy load exercise conditions). In order
to gather more available data for evaluating the temperature, we included two pre-post studies
containing a resting condition using valid methodology and exact temperature measurements. This
clearly reduced the heterogeneity index I2.For the meta-analysis of the resultant CO2-blood-content
the joint evaluation of different experimental CO2 measurements (PtCO2, ETCO2, PaCO2) in mmHg
was justified by the following facts:
1) “ETCO2 and PtCO2 measurements both provide an estimation of PaCO238.
2) "End-tidal CO2 (ETCO2) has been considered as a reliable estimate of arterial PCO2, in healthy
subjects" 39.
Consequences of wearing face masks
3) "PtCO2 reliably reflects PaCO2, irrespective of sensor location" 40.
4) "Transcutaneous CO2 (PtCO2) devices provide another option for the continuous non-invasive
estimation of PaCO2, overcoming the limitations posed by end-tidal CO2 analysis" 39.
5) "ETCO2 monitoring tends to underestimate PaCO2 levels" 38.
For meta-analysis of measured sensations, all studies in which measurements were mainly taken
during physical activity were included. This helped to ensure comparability, lower heterogeneity
and the above mentioned aims to draw conclusions on the general population under conditions
resembling real life settings. However, an exemption was made for the sensation ‘discomfort’: To
allow evaluable study numbers, we included one pre-post study with resting condition, however,
with valid methodology and exact discomfort evaluations 41. Even if this study had not been
included, the result would be significant and unambiguous, however with a slightly larger 95% CI.
Our systematic review also referenced studies aiming to assess the prevalence of sensations and
symptoms under mask use. Therefore, we conducted an additional meta-analysis of these
observational studies to document the pooled prevalence in mask use. Prevalence was calculated as
total number of symptoms per 100 mask wearers. In studies where the standard error (SE) was not
reported, we calculated it from the prevalence using the following formula: SE = √p (1-p) / n with a
95% CI = p ± 1.96 X SE; where, p = Prevalence. This statistical approach to quantify a pooled
prevalence from observational studies has been previously reported 34. Meta-analysis was performed
using RevMan (Version 5.4.1). The heterogeneity of each meta-analysis was assessed and then the
random effects model was used to calculate the pooled prevalence. We conducted subgroup analysis
where possible for mask type (N95/surgical). Funnel plots were used to study the possibility of
publication bias as described above.
The inclusion of observational studies, particularly for the prevalence analysis in our meta-analysis
is justified because these are particularly suitable to investigate exposures that are difficult or
impossible to investigate in randomised controlled trials (RCTs), e.g. air pollution or smoking. In
addition, observational studies are important to investigate causes with a long latency period, such
as carcinogenic effects of environmental exposures or drugs 42. Thus, possible adverse long-term
effects of masks, i.e. comparable to the environmental hazards, appeared to be particularly
detectable through observational studies.
Finally, the random statistical control calculations of our results were performed for quality
assurance via the R software (R Foundation for Statistical Computing, Vienna, Austria, version
4.0.1) and packages metafor, dmetar, meta 30. Knapp-Hartung adjustments to control for the
uncertainty in the estimate of the between-study heterogeneity were used in these calculations
which are controversial as they result in wider confidence intervals and are also suspected to be
anti-conservative even though the effects are very homogeneous 30.
Results
General findings
Literature characteristics
Of the 2168 screened records, 54 studies were included for qualitative analysis (see extraction
tables, Table 1) and 37 for statistical meta-analysis (Figure 1). Among the 54 studies, 23 were
intervention studies, and 31 were observational studies. The 23 intervention studies consisted of 14
randomised controlled trials (RCT´s) and 9 non-randomised controlled trials (nRCT´s). Of the 31
observational studies, 17 works raised measured values, and 14 were questionnaire studies.
Consequences of wearing face masks
Table 1 A-C: Overview of 54 included studies. A randomised controlled trials, B non-randomised controlled trials and C observational studies
Table 1A: Included 14 randomised controlled trials
Author and year Study design Intervention/control Sample size Time Outcomes
Bertoli 2020 Randomized, two-period cross-over
self-control trial
Wearing N95 respirator vs no facemask during indirect
calorimetry
N=10 5 min oxygen consumption (VO2),
carbon dioxide production
(VCO2),Resting Energy
Expenditure (REE)
Butz 2004 Blinded, randomized cross over study Wearing two types of surgical masks
vs no mask
N=15 30 min CO2 under masks,
PtCO2(partial transcutaneous
CO2 pressure) while wearing
masks for 30 min, HR, RR
(respiratory rate),SpO2
Dirol 2021 Prospective randomized cross-over
study
Six-minute walking test (6MWT) with and without surgical
mask. Mask-discomfort questionnaire was applied before and
after 6 MWT with the mask
N=100 6 min RR, HR, SpO2, EtCO2,
discomfort questionnaire
Fikenzer 2020 Prospective cross-over study Wearing no mask (nm) vs surgical mask (sm) vs
FFP2/N95 mask (ffpm), cardiopulmonary and metabolic
responses
monitored by ergo-spirometry and impedance cardiography
N=12 10 min FVC (forced vital capacity),
FEV1 (forced expiratory
volume in 1 s), Tiffenau index,
peak expiratory flow (PEF),
HR, stroke volume, cardiac
output, arterio-venous oxygen
content difference, systolic
blood pressure (SBP), diastolic
blood pressure (DBP),
ventilation in liters/minute
(VE), RR, tidal volume (VT),
pH, partial pressure of carbon
dioxide (PaCO2), partial
pressure of oxygen (PaO2),
lactate Pmax, Pmax/kg,
VO2max/kg, heart rate recovery
(HRR): HRR-1 min, HRR-5
min.
Discomforts (VAS): humid,
hot, breath resistance, itchy,
tight, salty, unfit, odor,fatigue,
overall discomfort.
Georgi 2020 Prospective randomized cross-over
study
wearing no mask (nm) vs community vs surgical mask (sm)vs
FFP2/N95 mask (ffp treadmill: baseline, 50 W, 75W,100W)
N=24 9 min HR, RR, SBP,DBP,
PtCO2,SpO2,
main symptoms questionnaire
Goh 2019 Randomized, two-period cross-over Wearing N95 respirator vs wearing N95 respirator with microfan N=106 15 min EtCO2, comfort level with
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
self-control trial vs wearing no facemask during common physical activities visual analogue scale (VAS)
Hua 2020 Prospective randomized crossover
trial
Two and 4 hours after donning the masks, adverse reactions and
perceived discomfort and noncompliance were measured.
N=20 240
min
Skin parameters: Skin
hydration, transepidermal water
loss, erythema, pH and
sebum secretion
Kim J.H. 2013 Randomized, self-control trial Wearing N95 respirator (partly with exhalation valve) vs wearing
no facemask (NM) during a low-moderate work-rate (5.6km/h)
N=20 60 min HR, RR, transcutaneous carbon
dioxide, SpO2
Kim J.H. 2015 Randomized, two-period controlled
trial
Wearing N95 respirator and no mask during one hour of mixed
sedentary activity and moderate exercise during pregnancy vs
non pregnant women
N= 16 vs 16 60 min SBP, DBP, mean arterial
pressure, HR, stroke volume,
cardiac output, total peripheral
resistance,
RPE, SpO2, PtCO2
Kim J.H. 2016 Randomized, self-control trial Wearing N95 respirator vs wearing P100 respirator vs wearing no
mask during 1 hour of treadmill exercise (5.6 km/h) in an
environmental chamber (35°C, relative humidity 50%)
N=12 60 min Fit factor, rectal temperature,
mean skin temperature, facial
skin temperature under
respirator, SpO2, PtCO2, HR,
RR, breathing comfort, thermal
sensation,exertion (Borg scale)
Mapelli 2021 interventional, prospective,
randomized, double-blind and cross-
over study
Wearing no mask surgical mask or N95 mask and performing
consecutive cardiopulmonary exercise tests (CPETs) at least 24
hours apart but within 2 weeks
N=12 10 min Ventilation (VE), Oxygen
intake VO2, VCO2 production,
respiratory gases,: exspiratory
O2 (ETO2) and exspiratory
CO2 (ETCO2), Heart rate
(HR), hemoglobin saturation
(SaO2), blood pressure (DBP
and SBD), dyspnea (Borg
scale), Spirometry,
Maximal Inspiratory pressure
(MIP) and Maximal Expiratory
Pressure (MEP)
Roberge 2014 Randomized, two-period controlled
trial
Wearing an N95 FFR during exercise and postural sedentary
activities over a 1-hour period on pregnant women vs control
N= 22/22 60 min Core temperature, cheek
temperature, abdominal
temperature, HR, RR, RPE,
perceived heat (RHP)
Wong A.Y.-Y 2020 Randomized, two-period self-
controlled trial
Wearing a facemask vs not wearing a facemask during graded
treadmill (10% slope) walking at 4 km/h for 6 min
N=23 6 min HR, RPE
Zhang 2021 Prospective randomized cross-over
study
Exercises (cycle ergometer) with and without surgical masks
(mask-on and mask-off) were analyzed
N=71 8 min test duration, maximum power,
RPE score, Borg dyspnea scale,
Oxygen consumption (V. O2),
carbon dioxide production
(V.CO2), metabolic equivalent
(MET), respiratory exchange
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
rate (RER), and percentage of
oxygen uptake at anaerobic
threshold (AT) in predicted
maximal oxygen uptake,
inspiratory time (Ti), expiratory
time (Te), RR, VT, VE, end-
tidal oxygen partial pressure
(EtO2), EtCO2, oxygen
ventilation equivalent
(VE/V.O2), and carbondioxide
equivalent (VE/VCO2)
Legend:
AT, anaerobic threshold; DBP = diastolic blood pressure; EtCO2 = end-tidal CO2 partial pressure; ESRD = end stage renal disease; TEWL= trans-epidermal water loss; FEV1 = forced expiratory
volume in 1 sec; FVC = forced vital capacity; HCW = health care worker; HD=haemodialyis; HR = heart rate; MEP = maximal expiratory pressure, MET = metabolic equivalent; MIP =maximal
inspiratory pressure; PEF = peak expiratory flow; PetCO2 = end-tidal carbon dioxide pressure; PetO2 =end-tidal oxygen pressure ; PI = perfusion index; PPE = personal protective equipment;
PtCo2 = partial transcutaneous CO2 pressure; RER = respiratory exchange ratio; RPE = rated perceived exertion; RR = respiratory rate; RR =respiratory rate; SaO2 =hemoglobin oxygen
saturation; SBP = systolic blood pressure; SpO2 = oxygen saturation; Te= expiratory time; Ti = inspiratory time; Ttot =Inspiratory + expiratory time; TV = tidal volume; V˙CO2 =carbon dioxide
production; V˙O2 = oxygen uptake; VE = ventilation in liters/min; VE = ventilation; VT = tidal volume,
Table 1B: Included 9 non-randomised controlled trials
Author and year Study design Intervention/control Sample size Time Outcomes
Bharatendu 2020 Cross-sectional self-control trial Wearing N95 respirator vs no facemask N=154 5 min Mean flow velocity (MFV),
Pulsatility index, end-tidal
carbon dioxide partial pressure
(EtCO2)
Coniam 2005 Two-period controlled trial Wearing surgical masks (WM) vs no facemask (NM) during oral
examination
N=186 10 min Pronunciation, vocabulary,
grammar, comprehensibility,
audibility
Epstein 2020 Multiple cross-over, self-control trial Wearing N95 respirator vs wearing surgical mask vs no facemask
during maximal exercise test
N16 18 min HR, RR, SpO2, rated perceived
exertion (RPE), end-tidal
carbon dioxide (EtCO2)
Lee 2011 Two-period self-controlled trial Wearing N95 respirator vs no facemask during rhinomanometry N=14 30 sec Inspiration breathing resistance
increment, expiration breathing
resistance increment, breathing
volume decrement
Roberge 2010 Multiple cross-over, self-control trial Wearing an N95 FFR vs N95 FFR with exhalation valve vs no
mask during 1-hour treadmill walking sessions, at 1.7 miles/h and
at 2.5 miles/h
N=10 60 min FFR dead space gases, CO2
saturation, O2 saturation, RR,
VT, VE, HR
Roberge 2012 Two-period self-control trial Wearing a surgical mask for 1 hour during treadmill exercise at
5.6 km/h vs the same exercise with no mask
N=20 60 min Core temperature, cheek
temperature, abdominal
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
temperature, HR, RR, RPE,
Perceived heat (RHP)
Scarano 2020 Two-period self-controlled trial Wearing a surgical mask for 1 hour vs wearing N95 respirator for
1 hour vs baseline
N=20 60 min Humidity, heat, breathing
difficulty, discomfort, mask
touching, perioral temperature
Shenal 2012 Multiple cross-over self-controlled
field trial
Wearing one of seven respirators or medical mask during an 8-
hour working period vs no mask
N=27 480
min
Discomfort, RPE
Tong 2015 Two-period self-controlled trial Breathing through N95 mask materials during rest and exercise of
predetermined intensity vs breathing ambient air
N=19 50 min Oxygen consumption (VO2),
carbon dioxide production
(VCO2), VT, RR, VE, expired
oxygen (FeO2), expired carbon
dioxide (FeCO2), inspired
oxygen (FiO2), inspired carbon
dioxide (FiCO2)
Legend:
AT, anaerobic threshold; DBP = diastolic blood pressure; EtCO2 = end-tidal CO2 partial pressure; ESRD = end stage renal disease; TEWL= trans-epidermal water loss; FEV1 = forced expiratory
volume in 1 sec; FVC = forced vital capacity; HCW = health care worker; HD=haemodialyis; HR = heart rate; MEP = maximal expiratory pressure, TMET1 = metabolic equivalent; MIP =maximal
inspiratory pressure; PEF = peak expiratory flow; PetCO2 = end-tidal carbon dioxide pressure; PetO2 =end-tidal oxygen pressure ; PI = perfusion index; PPE = personal protective equipment;
PtCo2 = partial transcutaneous CO2 pressure; RER = respiratory exchange ratio; RPE = rated perceived exertion; RR = respiratory rate; RR =respiratory rate; SaO2 =hemoglobin oxygen
saturation; SBP = systolic blood pressure; SpO2 = oxygen saturation; Te= expiratory time; Ti = inspiratory time; Ttot =Inspiratory + expiratory time; TV = tidal volume; V˙CO2 =carbon dioxide
production; V˙O2 = oxygen uptake; VE = ventilation in liters/min; VE = ventilation; VT = tidal volume,
Table 1C: Included 31 observational studies
Author and year Study design Intervention/control Sample size Time Outcomes
Beder 2008 Longitudinal and prospective
observational study
Wearing surgical mask during major operations vs baseline N=53 60-240
min
SpO2,(oxygen saturation)
HR (heart rate)
Choudhury 2020 Prospective cohort study Wearing N95 respirator during light work vs wearing full PPE
during heavy work vs baseline
N=75 240
min
HR,SpO2, Perfusion Index (PI),
RPE (rated perceived exertion),
modified Borg scale for
dyspnoea
Foo 2006 Survey study Self-administered questionnaire
healthcare workers
N=322 480
min
Prevalence of adverse skin
reactions
Forgie 2009 Cross-sectional survey study Self-administered questionnaire N=80 Not
given
Mask/Shield preference
Mask results, Shield resul
Heider 2020 Cross-sectional survey study Validated Voice Handicap Index (VHI)-10 questionnaire
and self administered questionnaire
N=221 480
min
Vocal symptoms,
Spanish validated Voice
Handicap Index (VHI)-10
questionnaire
Islam 2022 Prospective cross-over self-control Wearing FFP2 (N95) mask for 30 mins under sitting condition in N = 10 30 min Saha Institute of Nuclear
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
study an air-conditioned room Physics, Department of Atomic
Energy, Government of India
Jafari 2021 Cross-sectional study Self-administered questionnaire,
SpO2, HR and venous blood samples
N=243 240
min
RR, HR, SpO2, salivary
metabolic signature
Kao 2004 Prospective observational study Wearing N95 respirator during haemodialysis vs baseline N=39 240
min
HR, RR, systolic blood
pressure (SBP), diastolic blood
pressure (DBP), PaO2, PaCO2
discomfort rates
Klimek 2020 Cross-sectional Survey study Visual Analogue Scales (VAS) to
document patient-reported symptoms and diagnostic findings
N=46 120
min
Visual Analogue Scales (VAS)
to
document patient-reported
symptoms of: rhinitis,
rhinorrhea. Mucosal irritation,
secretion and edema in nasal
endoscopy was graded
Kyung 2020 Prospective panel study Wearing N95 respirator during 6 minute walking test vs baseline N=97 6 min SBP, DBP, HR, RR, EtCO2,
SpO2,
Lan 2020 Cross-sectional Survey study Self-administered questionnaire N=542 360
min
Prevalence of adverse skin
reactions
Li 2005 Prospective observational study Exercise on a
treadmill while wearing the protective facemasks
N=10 100
min
HR, temperature and humidity
(outside and inside the
facemask), SBP, DBP,
mask outer humidity, face
microclimate humidity, chest
microclimate humidity, mask
outside temperature, face
microclimate temperature,
face skin temperature, chest
microclimate temperature,
subjective sensations:
humiditty, heat, breath
resistance, itching, tightness,
feeling salty, feeling unfit,
feeling odorous, fatigue,
overall discomfort
Lim 2006 Survey study Self-administered questionnaire N=212 240
min
Prevalence of headaches
Luckman 2020 survey study
using online experimental
setting
Self-administered questionnaire
and experimental online setting
N=400 Not
given
Risk compensation with
reduced physical distancing
(standing, sitting, walking)
Matusiak 2020 Cross-sectional Self-administered questionnaire N=876 Not Difficulty in breathing,
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
Survey study given warming/sweating glasses
misting up, slurred speech, itch
Mo 2020 Retrospective observation cross over
cohort study
Wearing surgical mask vs not wearing: compare to former
hospiatlisations.
Including criteria: Patietns who were hospitalized three or more
times and atr least two times before mask mandates
N=23 7 min Vital signs: temperature, HR,
RR, SBP, DBP, serum and
blood gas analysis, inpatient
days (days).clinical parameters,
including ion concentration of
serum, vital signs,
inflammation markers and
artery blood gas.
Naylor 2020 Survey study Self-administered online questionnairess. N=129 Not
given
Effects of certain aspects of
lockdown, including face
masks, social distancing, and
video calling, on participants
behavior, emotions, hearing
performance, practical issues,
and tinnitus.
Ong 2020 Cross-sectional survey study Self-administered questionnairee. N=158 360
min
PPE usage patterns,
occupation, underlying
comorbidities
Park 2020 Prospective cohort study Wearing KF94 respirator for 6 hours vs baseline N=21 360
min
Skin temperature increase,
skin redness, skin hydration,
sebum level, skin elasticity,
trans-epidermal water loss
Pifarre 2020 Prospective trial No mask baseline vs.
Mask baseline.
Subjects wearing a mask immediately after a 21-flex test
performed the Ruffier protocol
N=8 5-7
min
PaO2, PaCO2, SpO2, HR
Prousa 2020 Cross-sectional survey study Self-administered questionnaire N=1010 Not
given
Wearing time, discomfort
Stress, Tricks,
psychovegetative complaints,
positive feelings,
agression, depression
Ramirez-Moreno
2020
Cross-sectional study in healthcare
workers
Self-administered questionnaire N=306 420
min
Work type, type of face mask,
number of hours worn per day
(SD). pre-existing headache,
comorbidity, other symptoms,
Sleep disturbance, loss of
concentration, irritability,
photophobia, sonophobia,
sickness/vomiting
Rebmann 2013 Multiple cross-over, self-control trial Wearing only an N95 or an N95 with mask overlay for a 12-hour N=10 720 h SBP, DBP, CO2 saturation,
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
shift vs baseline SpO2,
HR, headache, nausea, light-
headedness, visual challenge
Rosner 2020 Cross-sectional study in healthcare
workers
Self-administered questionnaire N=343 360
min
Acne, headache, skin
breakdown (nose bridge,
cheeks, chin. behind ears),
impaired cognition
Sukul 2022 Two-period controlled trial Wearing a scurgical or N95 mask during rest (young to mid-aged
adults were measured for 30 min and older adults were measured
for 15 min)
N=30 15-30
min
Exhaled breath profiles within
mask space by high-resolution
real-time mass-spectrometry
(PTR-ToF-MS): aldehydes,
hemiterpene, organosulfur,
short-chain fatty acids,
alcohols, ketone, aromatics,
nitrile and monoterpene.
Haemodynamic parameters:
SpO2, PETCO2, HR, RR,
SBP, DBP, cardiac ouput,,
exhaled oxygen, humidity.
Szczesniak 2020 Survey study Self-administered online questionnaire
After mask restrictions vs before mask restrictions
N=1476 vs
564
Not
rgiven
Employment status, place of
residence, worktime per week,
somatic symptoms, anxiety and
insomnia, aocial dysfunction,
depression
Szepietowski 2020 Survey study Self-administered online questionnaire N=2307 Not
given
itch, mask types used,
duration of mask use per day
Techasatian 2020 Prospective cross-sectional survey
study
Self-administered questionnaire N=833 480
min
Factors associated with adverse
skin reaction, risk factors for
adverse skin reaction,
differences between HCW and
non-HCW
Thomas 2011 Two-period controlled trial Comparing the ability to accurately record 20 randomized
aviation terms transmitted over the radio by a helicopter
emergency medical services (HEMS) pilot wearing a surgical
facemask and six different N95s with and without the aircraft
engine operating
N=3 Not
given
Accurately record 20 terms
transmitted over the radio by
(HEMS) pilot wearing a
surgical facemask or N95 mask
Toprak 2021 Prospective observational study surgical vs N-95 mask
n=149 vs n=148
N=297 35 min Maternal vital signs: SBP, DBP,
HR, RR, fever centigrade,
SpO2
Tornero-Aguilera
2021
Two-period controlled trial Wearing a surgical facemask vs not wearing a facemask during
150 min university lessons
N=50 150
min
Mental fatigue perception,
reaction time (ms) SpO2,
mean RR (ms), mean HR
Consequences of wearing face masks
Author and year Study design Intervention/control Sample size Time Outcomes
(bpm)
square root of the mean value
of the sum of squared
differences of all successive R-
R intervals (RMSSD) (ms), low
frequency (LF) and high-
frequency (HF) normalized
units (n.u.), SD1 (ms), SD2
(ms)
Legend:
AT, anaerobic threshold; DBP = diastolic blood pressure; EtCO2 = end-tidal CO2 partial pressure; ESRD = end stage renal disease; TEWL= trans-epidermal water loss; FEV1 = forced expiratory
volume in 1 sec; FVC = forced vital capacity; HCW = health care worker; HD=haemodialyis; HR = heart rate; MEP = maximal expiratory pressure, TMET1 = metabolic equivalent; MIP =maximal
inspiratory pressure; PEF = peak expiratory flow; PetCO2 = end-tidal carbon dioxide pressure; PetO2 =end-tidal oxygen pressure ; PI = perfusion index; PPE = personal protective equipment;
PtCo2 = partial transcutaneous CO2 pressure; RER = respiratory exchange ratio; RPE = rated perceived exertion; RR = respiratory rate; RR =respiratory rate; SaO2 =hemoglobin oxygen
saturation; SBP = systolic blood pressure; SpO2 = oxygen saturation; Te= expiratory time; Ti = inspiratory time; Ttot =Inspiratory + expiratory time; TV = tidal volume; V˙CO2 =carbon dioxide
production; V˙O2 = oxygen uptake; VE = ventilation in liters/min; VE = ventilation; VT = tidal volume,
Consequences of wearing face masks
Quality appraisal
The quality of the studies was not very homogeneous. The quality assessment identified some
studies with low and average quality, which were excluded from the meta-analysis. We included
only high-quality studies in our meta-analysis of RCT´s and nRCT. The quality of the included
observational studies is predominantly good. Table 2 A-D summarises the results of the quality
appraisal of the included research papers.
Mask type
Of the 37 meta-analytically evaluated studies, 31 examined the N95 mask, 19 the surgical mask
with 1 not reporting on the specific type of mask due to the predominantly psychological research
topic. There were 14 Studies evaluating both mask types (surgical and N95) and we compared the
results in a separate meta-analysis (see below, Meta-analysis of N95 mask vs surgical mask).
Participants and time
8641 subjects were used to conduct the meta-analysis totalling 22127 individual
measurements/surveys.
This population consisted of young (age=34.8±12.5) and predominantly female subjects (m=2482,
f=6159).
Physiological, physical and biochemical data was used in the meta-analyses comprising of 934
participants and 3765 experimental measurements.
The pooled prevalence data was drawn from a study population of n=8128 and included 17383 data
entries.
Most of the 37 studies, evaluated in meta-analyses included healthy participants. Twelve studies
were conducted in health care workers (32%).
Two studies (5%) included chronic obstructive pulmonary disease (COPD), one study on
haemodialysis patients, another study included children (3%) and 4 studies involved pregnant
women (11%).
The median experimental time of the studies included in the meta-analyses (mostly controlled trials)
on physiological, physical, and chemical face mask effects was 18 minutes with an interquartile
range (IQR) of 50 minutes (min.: 6 minutes, max.: 360 minutes). There was a major deviating mask
exposure duration with exceptions (mean of 45.8 minutes with a standard deviation of 69.9
minutes). Therefore, the mean was not an appropriate parameter to characterise this distribution).
The study with the longest experimental duration (360 minutes, observational) included only 21
healthy participants, which corresponds to 2.2% of the total population studied (n=934).
Interestingly, the studies on symptoms (including many observational studies) had significantly
longer observation times and a mean of 263.8±170.3 minutes (median 240, IQR 180) in a total of
n=8128 participants.
Consequences of wearing face masks
Table 2 A-D: Summary of the quality appraisals for the included studies. Part A shows the quality
analysis of RCTs with Cochrane RoB tool++, while Part B lists the results of the quality analysis of
nRCTs with CASP checklist. Part C is on the quality analysis of observational (non questionnaire)
studies with CASP checklist. Part D documents the quality analysis of the questionnaire studies by
means of a similar checklist.
Table 2 A: Quality appraisal of randomised controlled trials
Publication
Selection Bias
Performance Bias
Detection Bias
Attrition Bias
Reporting Bias
1. Random Sampling
2. Allocation Blinding
3.Blinding for Intervention
4. Evaluation Blinding
5. Incomplete Data
6. Selective Reporting
7. Other Bias
Bertoli 2020 LR LR HR HR LR UC LR
Butz 2005 LR LR HR LR UC UC UC
Dirol 2021 LR LR HR LR LR LR LR
Fikenzer 2020 LR LR HR LR LR LR LR
Georgi 2020 LR LR HR LR LR UC LR
Goh 2019 LR LR HR LR LR LR LR
Hua 2020 LR LR HR LR UC UC LR
Kim J.H. 2013 HR LR HR LR LR LR LR
Kim J.H. 2015 LR LR HR LR LR UC LR
Kim J.H. 2016 LR LR HR LR LR UC LR
Mapelli 2021 LR LR HR LR LR UC LR
Roberge 2014 LR LR HR LR LR UC LR
Wong A.Y.-Y 2020 LR LR HR LR LR UC LR
Zhang 2021 LR LR HR LR LR LR LR
Legend: LR=low risk, HR=high risk, UC=Unclear
Consequences of wearing face masks
Table 2 B: Quality appraisal of non-randomised controlled trials
Publication
1. clear focus?
2. appropriate methods?
3. recruitment comprehensible?
4. valid measurement of exposure?
5. valid measurement of outcome?
6. equality of groups?
7. confounders taken into account?
8. sufficient size and significance of the effect?
9. credibility of the results?
10. transferability to other populations? clear focus?
11. comparability with existing evidence?
Bharatendu 2020 Y Y Y Y UC Y Y Y UC Y UC
Coniam 2005 UC N Y Y Y UC UC Y Y Y UC
Epstein 2021 Y Y Y Y Y Y UC N Y Y Y
Lee 2011 Y Y Y Y N Y Y N UC Y UC
Roberge 2012 Y Y Y Y Y Y Y Y N Y Y
Roberge 2010 Y Y Y Y Y Y Y N Y Y Y
Scarano 2020 Y Y Y Y Y Y UC Y Y Y UC
Shenal 2012 Y Y Y Y Y Y Y Y Y Y UC
Tong 2015 Y Y Y Y N Y Y Y Y Y UC
Legend: Y=Yes, N=No, UC=Unclear
Consequences of wearing face masks
Table 2 C: Quality Appraisal of the Observational Studies
Publication
1. clear focus?
2. appropriate methods?
3. recruitment comprehensible?
4. valid measurement of exposure?
5. valid measurement of outcome?
6. equality of groups?
7. confounders taken into account?
8. sufficient size and significance of the effect?
9. credibility of the results?
10. transferability to other populations? clear focus?
11. comparability with existing evidence?
Beder 2008 Y Y N Y Y UC N Y Y Y Y
Choudhury 2020 Y Y Y Y Y N Y Y Y N N
Islam 2022 Y Y Y Y Y Y UC Y UC Y Y
Jafari 2021 Y Y Y Y Y Y UC Y Y N UC
Kao 2004 Y Y Y Y Y Y Y Y Y N UC
Klimek 2020 Y Y Y Y Y Y UC Y Y Y UC
Kyung 2020 Y Y Y Y Y Y Y Y Y N UC
Li 2005 Y Y Y Y Y Y Y UC Y Y UC
Luckman 2020 Y UC N Y Y Y Y Y Y Y UC
Mo 2020 Y Y Y Y Y UC UC Y Y Y Y
Park 2020 Y Y Y Y Y Y N Y Y Y UC
Pifarre 2020 Y Y Y Y Y Y Y Y Y Y UC
Rebmann 2013 Y Y Y Y Y Y N N Y N Y
Sukul 2022 Y Y Y Y Y Y Y Y Y Y UC
Thomas 2011 Y Y Y Y Y N Y Y Y Y UC
Toprak 2021 Y Y Y Y Y UC N Y Y N Y
Tornero-Aguilera 2021 Y Y Y Y Y Y N Y Y Y Y
Legend: Y=Yes, N=No, UC=Unclear
Consequences of wearing face masks
Table 2 D: Quality Appraisal of the Questionnaire Studies
Publication
Study
design
Validity and
reliability
Questionnaire
quality
Questionnaire
design
Sample Distribution and
response
Analysis Results Summary and
recommendation
Was a questionnaire study an appropriate method?
Are the results valid and realistic?
Does the questionnaire used provide reliable results?
Were sample questions provided?
Are the questions formulated in a clear and
understandable way?
Details on how the questionnaire was prepared?
Was the questionnaire prepared in an appropriate
manner?
Was the sample sufficiently large and representative?
Was information provided on how the questionnaire
was made available?
Was information provided on response rates and
exclusion criteria?
Was potential response bias discussed?
Were the results analysed appropriately?
Were all relevant results published?
Were both significant and non-significant results
published?
Were results adequately interpreted?
Does the summary reflect the results of the study?
Were the results placed in context with existing
literature?
Foo
2006
Y Y UC N UC N UC Y Y Y N Y Y Y Y Y Y
Forgie
2009
Y Y Y Y Y Y Y Y Y Y N UC Y N Y Y Y
Heider
2020
Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
Lan 2020 Y Y UC N UC N UC Y Y Y N Y Y Y Y Y Y
Lim
2006
Y Y UC N UC N UC Y N Y N Y Y Y Y Y Y
Matusiak Y Y UC N UC Y Y Y Y Y N Y UC Y Y Y Y
Consequences of wearing face masks
2020
Naylor
2020
Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y N
Ong
2020
Y Y UC N UC N UC Y Y Y N Y Y Y Y Y Y
Prousa
2020
Y N Y Y Y Y Y N Y N N Y Y Y N Y UC
Ramirez
2020
Y Y UC N UC Y Y Y Y Y N Y Y Y Y Y Y
Rosner
2020
Y Y UC N UC N UC Y Y N N Y Y Y Y Y Y
Szczesniak
2020
Y N UC N UC N UC Y Y N N Y UC N N Y Y
Szepietowski
2020
Y Y UC N UC Y Y Y Y N N Y Y Y Y Y Y
Techasatian
2020
Y Y UC N UC N UC Y Y N N Y Y Y Y Y Y
Study
design
Validity and
reliability
Questionnaire
quality
Questionnaire
design
Sample Distribution and
response
Analysis Results Summary and
recommendation
Legend: Y=Yes, N=No, UC=Unclear
Consequences of wearing face masks
Qualitative evaluation
Of the 54 included studies, 51 reported numerous adverse mask effects across multiple clinical
disciplines, as already compiled in a previous scoping review 8. Also fourteen of the 17 studies,
which were not included in the meta-analysis reported those numerous mask effects.
Overall, our systematic review found mask related symptoms that can be classified under the
previously described Mask-Induced Exhaustion Syndrome (MIES) 8, with typical changes and
symptoms that are often observed in combination.
Among the included 54 studies (Table 1), we detected and compiled reports on frequently
statistically significant physiological and psychological changes (p<0.05) belonging to the MIES
such as:
-increase in breathing dead space volume43,44
-increase in breathing resistance 45–49
-increase in blood carbon dioxide 20,43–45,50–64
-decrease in blood oxygen saturation 20,44,45,48,49,52,53,55,56,58,60,61,63–68
-increase in heart rate 20,44,47,49,52,56–58,61,62,65,67–69
-decrease in cardiopulmonary capacity 45,48,64
-changes in respiratory rate 44,45,48,52,53,57,58,62,64,66,67
-shortness of breath and difficulty breathing 41,45,47,52,53,55,58,59,61,61,62,66,70–73
-headache 50,53,61,70,72,74–78
-dizziness 53,58,66
-feeling hot and clammy 44,45,47,52,55,62,71,73
-decreased ability to concentrate 68
-decreased ability to think 58,61,68,78
-drowsiness 78
-impaired skin barrier function 41,78,79
-itching 45,41,47,52,71,79–83,75
-acne, skin lesions and irritation 79,41,58,71,62,78,82,75
-false sense of security 84,85
-overall perceived fatigue and exhaustion 70,52,45,53,66,55,56,47,48,44,62,86,63,69,64,61.
Moreover, we could objectify additional symptoms of the MIES as follows:
-decrease in ventilation 45,48,64
-increase in blood pressure 20,45,47,48,52,58,59,64,67
-increase of measured temperature of the skin under the mask 55,62,73,87
-increase of measured humidity of the air under the mask 55,73,87
-communication disturbance 61,71,78,88,89
-voice disorder 71,90
-perceived discomfort 41,45,52,73
-increased anxiety 72,88,91
-increased mood swings or depressive mood 72,88,90,91
and:
-changes in microbial metabolism 20,92
However, three studies (6% of the included papers) describe the absence of adverse or even positive
mask effects 85,93,94.
Consequences of wearing face masks
Results of the meta-analysis
In the meta-analytic evaluation, we found biochemical, physiological, physical, and perceptual
symptoms with face mask use. We were also able to meta-analyse the pooled prevalence of
symptoms. These results are presented in detail below.
Meta-analysis of biochemical effects of face masks
SpO2 and face masks
The results are summarised in Figure 2A.
In a pooled analysis, blood oxygen saturation is significantly lowered during mask use. This could
be found for general mask use (p=0.0004, SMD= -0.24, 95% CI -0.38 to -0.11, Z=3.53, I2=0%).
The Eggers' test does not indicate the presence of funnel plot asymmetry (t(df=11)=-0.70, p=.50).
This was also confirmed in the subgroup analysis for N95 mask use (p=0.001, SMD= -0.3, 95% CI
-0.49 to -0.12, Z=3.19, I2=0%), but not for surgical mask use (p=0.08, SMD= -0.17, 95% CI [-0.37;
0.02], Z=1.77, I2=0%). However, 7 of 9 studies in the N95 mask meta-analysis contain the "0" in
the confidence interval and are not significant because of n being too small (sample size). From the
pooled analysis, it seems that N95 mask use may be responsible for a larger SpO2 drop than surgical
masks.
In a separate meta-analysis of pre-post studies an equally significant drop in SpO2 was found when
using a mask (p=0.0001, SMD= -1.24, 95% CI -1.87 to -0.61, Z=3.87, I2=80%) especially in the
subgroup of N95 masks (p=0.02, SMD= -1,24, 95% CI -2.26 to -0.22, Z=2.37, I2=89%), yet with a
high heterogeneity.
Blood CO2 content and face masks
The results are summarised in Figure 2B.
In a pooled analysis, blood carbon dioxide content was found to be significantly elevated in mask
use. This was perceived for general mask use (p=0.0001, SMD=0.64, 95% CI 0.31 to 0.96,Z=3.86,
I2=81%). The Eggers' test does not indicate the presence of funnel plot asymmetry (t(df=11)=-0.87,
p=.40). This was also confirmed for N95 mask use (p=0.003, SMD=0.78, 95% CI 0.28 to
1.29,Z=3.02, I2=84%) and also for surgical mask use (p<0.00001, SMD=0.42, 95% CI 0.24 to 0.59,
Z=4.65, I2=0%).
There was no significant difference between the pooled effect sizes of N95 and surgical masks
(Q(df=1)=3.09, p=.08). Further separate pooled evaluations were also carried out for PtCO2, ETCO2
and PaCO2, for each surgical and N95 masks with a significant increase in blood CO2 with
predominantly low heterogeneity.
Even in a separate meta-analysis of pre-post studies with high heterogeneity, a significant increase
in blood carbon dioxide content was found when using a mask (p=0.003, SMD=1.44, 95% CI 0.49
to 2.39, Z=2.97,I2=94%) and also in the subgroup of N95 masks (p=0.02, SMD=1.51, 95% CI 0.24
to 2.78, Z=2.34,I2=96%).
Interestingly, 11 of 17 studies include "0" in the confidence interval and the majority showed no
effect. The studies that showed clear effects (not including 0 in their confidence interval) differed
from those that showed no certain effects as they either included N95 and/or pregnant women or
children. The study by Dirol et al is an exception but has a sample size of n=100 for surgical masks.
Apparently, it takes N95 masks and vulnerable populations or appropriately large samples in
surgical masks to make the effects more quantifiable and precise.
Consequences of wearing face masks
Accordingly, in the surgical mask meta-analysis, studies that included "0" in the confidence interval
were of small sample size, with a mean of n=24 and a median of n=14. The advantage of a meta-
analysis is to combine several imprecise effects into a more precise overall effect 30.
Meta-analysis of physiological effects of face masks
Ventilation(VE) in L/min and face masks
The results are summarised in Figure 3A.
Despite compensatory mechanisms, breathing volume (L/min) is significantly lowered during mask
use in the pooled analysis.
This was not only verified for general mask use (p<0.00001, SMD= -0.72, Z=5.36, 95% CI -0.99 to
-0.46, I2=0%) in studies evaluated with an overall low heterogeneity (I2=0), but also for surgical
(p<0.0001, SMD= -0,54, 95% CI -0.94 to -0.35, Z=4.32, I2=0%) and N95 mask use (p=0.0007,
SMD= -1.06, 95% CI -1.68 to -0.45, Z=3.39, I2=0%). Both studies had an overall low
heterogeneity(I2=0).
On average, masks reduce respiratory minute volume by -19% according to our meta-analysis, and
by as much as -24% for N95 masks; the difference between surgical and N95 masks is -10%
respiratory minute volume.
Respiratory rate and face masks
The results are summarised in Figure 3B.
Interestingly, no statistical difference regarding respiratory rate was determined in mask use in the
pooled analysis.
Even in the subgroups containing N95 and surgical masks, no difference compared to the no mask
condition could be found.
Systolic blood pressure (SBP) and masks
The results are summarised in Figure 4A.
A significant elevation in systolic blood pressure was found for mask users with p=0.02, SMD=
0.17, 95% CI 0.03 to 0.32, Z=2.39 and I2=0% in the pooled analysis. It is a small effect and in 9 out
of 10 studies insignificant, including 2 with higher n in each case. The Eggers' test does not indicate
the presence of funnel plot asymmetry (t(df=8), p=.27). This was verified in the subgroup analysis
for surgical masks (p=0.02, SMD= 0.21, 95% CI 0.03 to 0.39, Z=2.33, I2=0%). In studies evaluating
both mask types (surgical and N95) the N95 mask always yielded a higher SBP than the surgical
mask. However, this effect was not statistically significant. There is no significant difference
between the pooled effect sizes of N95 and surgical masks (Q(df=1)=0.98, p=.32).
Heart rate and masks
The results are summarised in Figure 4B.
No statistically significant difference regarding the heart rate during mask use was found in the
pooled analysis. The Eggers' test does not indicate the presence of funnel plot asymmetry (t(df=14),
p=.94). However, in the subgroup analysis containing surgical and N95 masks, only for the N95
mask condition a weak significance for a slight increase in heart rate could be found (p=0.02,
SMD= 0.22, 95%CI 0.03 to 0.41, Z=2.30 and low heterogeneity of studies with I2=0). There is no
significant difference between the pooled effect sizes of N95 and surgical masks (Q(df=1)=1.26,
p=.26).
Consequences of wearing face masks
Meta-analysis of physical effects of face masks
Skin temperature and face masks
The results are summarised in Figure 5A.
Skin covered by mask has a significantly higher temperature during rest and activity. This could be
found for general mask use (p=0.005, SMD=0.80, 95% CI 0.23 to 1.38, Z=2.81. I2=72%), for N95
mask use (p=0.02, SMD=0.72, 95% CI 0.12 to 1.32, Z=2.35, I2=55%), but not for surgical mask use
(p=0.21, SMD=0.96, Z=1.26, I2=90%).
Humidity and face masks
The results are summarised in Figure 5B.
The dead space covered by mask has a significantly higher humidity in the pooled analysis.
This could be found for general mask use with p<0.00001, SMD=2.24, 95% CI 1.32 to 3.17,
Z=4.75 and I2=50%).
Meta-analysis of measured symptoms and sensations during face mask use
Discomfort and face masks
The results are summarised in Figure 6A.
Perceived discomfort is significantly higher in mask use during rest and activity in the pooled
analysis.
This could be found for general mask use (p<0.0001, SMD=1.16, 95% CI 0.58 to 1.73, Z=3.94,
I2=74%), for N95 mask use (p<0.00001, SMD=1.98, 95% CI 1.37 to 2.59, Z=6.34, I2=0%) as well
as for surgical mask use (p<0.00001, SMD=0.71, 95% CI 0.46 to 0.96, Z=5.58, I2=0%).
Itch and face masks
The results are summarised in Figure 6B.
In N95 mask use, the perceived itching was significantly elevated (p=0.003, SMD=2.65, 95% CI
1.21 to 4.09, Z=3.6, I2=83%) during activity according to the pooled subgroup analysis.
Although not statistically significant, an overall tendency for itching was found for general mask
use in the pooled analysis.
Exertion and face masks
The results are summarised in Figure 6C.
Perceived exertion is significantly higher in mask use during activity in the pooled analysis.
This could be found for general mask use (p<0.0001, SMD=0.90, 95% CI 0.58 to 1.23, Z=5.31.
I2=71%), for N95 mask use (p=0.002, SDM=1.19, 95% CI 0.43 to 1.95, Z=3.06, I2=81%) as well as
for surgical mask use (p<0.0001, SMD=0.63, 95% CI 0.40 to 0.87, Z=5.29, I2=24%). The Eggers'
test indicates the presence of funnel plot asymmetry (t(df=10)=2.68, p=.02). For N95 mask use
(p=0.002, SDM=1.19, Z=3.06, I2=81%) and this result was confirmed for surgical mask use too
(p<0.0001, SMD=0.63, Z=5.29, I2=24%). There is no significant difference between the pooled
effect sizes of N95 and surgical masks (Q(df=1)= 1.97, p=.16).
Shortness of breath and face masks
Consequences of wearing face masks
The results are summarised in Figure 6D.
Perceived shortness of breath is significantly higher during mask use during activity in the pooled
analysis (p=0.006, SMD=1.46, 95% CI 0.42 to 2.50, Z=2.75, I2=86%).
In the subgroup analysis for surgical and N95 masks, the masks always led to an increase in
perceived shortness of breath, but the number of studies that could be included was very limited and
no statistically significant results were found in the subgroup analysis.
Perceived heat and face masks
The results are summarised in Figure 6E.
Perceived heat is significantly higher during mask use with physical activity in the pooled analysis
(p=0.002, SMD=0.70, 95%CI 0.28 to 1.13, Z=3.27, I2=62%).
In the subgroup analysis containing surgical and N95 masks the heat perception was increased in
both mask types, but only for the surgical mask condition a statistical significance for an increase in
heat perception could be found (p=0.008, SDM=0.61, 95% CI 0.16 to 1.06, Z=2.66, I2=50%).
Perceived humidity and face masks
The results are summarised in Figure 6F.
Perceived humidity is significantly higher in mask use during activity according to the pooled
analysis (p=0.002, SMD=0.90, 95% CI 0.34 to 1.46, Z=3.17, I2=53%).
The subgroup analysis containing surgical and N95 masks was completed merely for surgical masks
due to lack of studies on N95 masks.
In the surgical mask condition a statistical significance for an increase in humidity perception could
be found (p<0.00001, SMD=0.63, 95% CI 0.36 to 0.90, Z=4.6, I2=0).
Meta-analysis of N95 mask vs surgical mask
The results are summarised in Figure 7A-C.
The N95 mask leads to measurably worse effects compared to the surgical mask. The blood
oxygenation is significantly decreased when using a N95 mask compared to a surgical mask with
p=0.003, SMD= -0.53, 95%CI -0.88 to -0.18, Z=2.98, I2=37%. The heart rate (p=0.01, SMD=0.25,
95% CI 0.05 to 0.45, Z=2.47, I2=0%), the perception of discomfort (p=0.02, SMD=3.07, 95% CI
0.52 to 5.61, Z=2.36, I2=95%) and humidity (p=0.02, SMD=0.59, 95% CI 0.09 to 1.10, Z=2.32,
I2=0%) increased in each case when the N95 mask was compared to the surgical mask. This trend
was also evident for CO2, minute volume, exertion, heat, shortened breath and systolic blood
pressure, but was not statistically significant due to the limited available studies.
Meta-analysis with pooled prevalence of symptoms during face mask use
The results are summarised in Figure 8.
The prevalence of headaches with mask use is significant in the majority of evaluated users
(n=2525), with a pooled prevalence of 62% (p<0.00001, 95%CI 0.48 to 0.75) and even 70%
(p<0.00001, 95%CI 0.52 to 0.88) with N95 mask use.
Acne when using a mask is significantly present in evaluated users (n=1489) with a pooled
prevalence of 38% in general mask use (p<0.00001, 95%CI 0.22 to 0.54).
Skin irritation occurrence when using a mask is significantly present in the evaluated users
(n=3046) with a pooled prevalence of 36% in general mask use (p<0.00001, 95%CI 0.24 to 0.49).
Consequences of wearing face masks
Shortness of breath rate when using a mask is significantly present in users (n=2134) with a pooled
prevalence of 33% in general mask use (p<0.00001, 95%CI 0.23 to 0.44) and 37% in N95 mask use
(p=0.01, 95%CI 0.07 to 0.67).
The prevalence of itch with mask use is substantial in evaluated users (n=5000), with a pooled
prevalence of 26% (p<0.00001, 95%CI 0.15 to 0.36). In the subgroup analysis, the pooled
prevalence for itch in N95 mask use was 51% (p<0.00001, 95%CI 0.47 to 0.55) while it was 17% in
surgical mask use (p<0.0001, 95%CI 0.09to 0.26). These results were confirmed in control
calculations using the R software.
The prevalence of voice disorders when using a mask is significant in evaluated users (n=1097)
with a pooled prevalence of 23% in general mask use (p=0.03, 95%CI 0.02 to 0.43), however with
high heterogeneity of the included studies.
The prevalence of dizziness when using a mask is significant in evaluated users (n=153) with a
pooled prevalence of 5% in general mask use (p=0.01, 95%CI 0.01 to 0.09). Due to the small
sample size (n) in the referred studies, there are wide confidence intervals. This results in a
significant, but not really pronounced overall result for dizziness.
Discussion
Besides the anticipated protection against the transmission of pathogens, face masks undoubtedly
impede natural breathing. Such respiratory impairments due to the “new-normal” lifestyle under the
present global pandemic have imposed potential adverse effects on our usual external and internal
respiration, affecting a wide range of physio-metabolic processes within various organ systems
and/or at cellular levels 8,20. Ensuing consequences were eventually observed at the physical,
psychological and social levels along with certain clinical symptoms in the individual human being
8. In this systemic review, we applied meta-analysis and comprehensive evaluations of physio-
metabolic, physical, psychological and clinical burdens of wearing face masks in the general
population. Restricting breathing through face masks has turned out to be a fundamental, incisive
intervention with possible negative effects on public health.
Physio-metabolic burden of masks
Our meta-analysis clearly depicts that masks significantly restrict O2 uptake and hinder CO2 release.
Based on the meta-analytic effect sizes defined by Cohen 95, the effect size for CO2 retention (as per
PtCO2, ETCO2 and PaCO2 outcomes) is medium for all mask types and is larger for N95 masks. The
effect size for O2 uptake disturbance (as per SpO2 outcome) is relatively smaller but highly
significant (p=0.0004) (Fig. 9A and Fig. 2 A, B). Such respiratory gas-exchange discrepancy can be
attributed to the constantly increased dead space ventilation volume 8,43,44,96,97 (i.e., continuous
rebreathing from the masks dead space volume) and breathing resistance 8,45–49. Continuous CO2
rebreathing causes the right-shift of haemoglobin-O2 saturation curve. Since O2 and CO2
homeostasis influences diverse down-stream metabolic processes, corresponding changes towards
clinically concerning directions may lead to unfavourable consequences such as transient
hypoxaemia and hypercarbia, increased breath humidity and body temperature along with
compromised physiological compensations etc..
Transient hypoxaemia
A progressive decrease in SpO2 is observed with respect to the duration of wearing a mask
20,52,55,57,58,60,65,70,98. The decline in SpO2 levels confirmed in our systemic-review supports the onset
and progression of oxidative stress (via significantly increased exhaled breath aldehydes –
originating from lipid peroxidation) reported by Sukul et al 20. Studies have shown that oxidative
Consequences of wearing face masks
stress (under hypoxic conditions) can inhibit cell-mediated immune response (e.g. T-lymphocytes,
TCR CD4 complex etc.) to fight viral infections, which may gradually lead to immune suppression
99,100. Arterial hypoxaemia increases the level of the hypoxia inducible factor-1α (HIF-1α), which
further inhibits T-cells and stimulates regulatory T-cells 100. This may set the stage for contracting
any infection, including SARS-CoV-2 and making the consequences of that infection much more
severe. In essence, masks may put wearers at an increased risk of infection and severity 99–101. A
recent review 102 by Serebrovska et al discusses a possible link between HIF-1α activation and cell
entry of SARS-CoV-2. If the cell is already under oxidative stress, activation of HIF-1α may
suppress important adaptive mechanisms e.g., autophagy or proteasomal proteolysis is leads to the
induction of necrosis and excessive cytokine production. Sturrock et al 103 demonstrated that the
SARS-CoV-2 receptor (e.g., ACE2 and TMPRSS2) expression by primary type II alveolar epithelial
cells increased significantly following exposure to hypoxic environments in vivo and in vitro.
Furthermore, recent research has demonstrated that the cellular entry of SARS-CoV-2 also depends
on many other receptor paths/routes (e.g., CD147, CD147 - spike proteins etc.), mediated by HIF-
1α upregulation 104–107. Therefore, the effect of even mild hypoxaemia for an extended span may
promote an infection risk along with metabolic stress e.g., due to altered pH via respiratory acidosis.
In line with that, Sukul et al 20 observed a significant decrease in exhaled volatile metabolites (e.g.
organosulfur and short-chain fatty acids) originating from the lower gut microbiota during face
mask use – indicating anaerobiosis, metabolic acidosis and possible immunosuppression. Even
marginal local effects of masks on salivary metabolites in young and healthy adults have indicated
alteration of microbial metabolic activity 92.
The findings of Spira 2022 10 from European data show that mask use correlates with increased
morbidity and mortality, which could be due to the above-discussed possible processes. Moreover,
prolonged hypoxic conditions and low oxygen levels pave the way for immunosuppression and
inflammation, which can promote the growth, invasion and spread of cancers 107–109.
However, further experimental studies are needed to prove that hypoxaemia under long-term mask
use may result in quantifiable changes in HIF-1α and immunosuppression – especially in elderly,
ill/comorbid and/or immunocompromised individuals.
Transient hypercarbia
In line with the increased dead space ventilation and consistently decreasing SpO2 level, CO2
inhalation elevates progressively during the course of wearing a mask, causing transient hypercarbia
20,52,55,57,58,60,98. Very recent experimental data exist on CO2 concentrations of concern in the air
breathed while wearing masks, especially in children 110,111. Systemic CO2 concentration exerts an
important influence on the intra- and extracellular pH. CO2 passes quickly through the cell
membranes to form carbonic acid, which releases protons and in excess causes acidosis 112–114. With
a prolonged CO2 burden the body uses the bones (CO2 storage) to regulate the blood pH:
bicarbonate and a positive ion (Ca2+, K+, Na+) are exchanged for H+. Accordingly, kidney and organ
calcification were frequently seen in animal studies on low-level CO2 exposure 115,116. Additionally,
CO2 in relationship with chronic and/or intermittent long-term exposure might induce pathological
states by favouring DNA alterations and inflammation 117,118. Moreover, inflammation is reported to
be caused by low-level CO2 exposure in humans and animals 118–122. Even slightly elevated CO2
induces higher levels of pro-inflammatory Interleukin-1β, a protein involved in regulating immune
responses, which causes inflammation, vasoconstriction and vascular damage 121. In addition,
carbon dioxide is also known as a trigger of oxidative stress caused by reactive oxygen species
(ROS) 117 including oxidative damage to cellular DNA 117,118.
Altogether, the possible damaging mechanism of CO2 affecting tissues is based on the conditions of
oxidative stress and acidosis with increased inflammation and apoptosis as described above 117,119–124.
In the long term, therefore, this could be possible during mask use even at blood-CO2 levels that do
Consequences of wearing face masks
not reach the thresholds. In spontaneously breathing subjects in a sitting position, exhaled CO2
profiles mirror the endogenous isoprene exhalation 12,125. Significant and progressively decreased
breath isoprene recently observed in adults 20 indicates the deoxygenation driven sympathetic
vasoconstriction in the peripheral compartments 126. Prolonged deoxygenation and CO2 re-breathing
therefore, may eventually lead to pulmonary vasoconstriction that may hinder blood-CO2 levels to
reach the thresholds. For instance, Sukul et. al also reported the presence of significant
hyperventilation state in older adults aged ≥ 60 years before wearing a face mask for the
participation in experiments. This indicates a compromised respiratory compensation of precedent
mask use (which was obligatory due to pandemic regulations at that time) by these subjects.
Physical burden of masks: Humidity and skin temperature
Together with the immune-inhibiting mechanisms mentioned above, we found some other possible
deleterious mask effects that contradict healthy natural breathing. The most prominent and extreme
effect was found in the increase of air humidity and skin temperature within the dead space of the
mask (Figure 9B and Figure 5). Increased humidity and temperature can increase droplet and
aerosol generation, which facilitate liquid penetration through the mask mesh. This not only
increases the chance of microorganism (fungal and bacterial pathogens) growth on and in masks 127–
129 causing increased risk for accumulation of fungal and bacterial pathogens 127,129 including
mucormycosis 130, but also leading to re-breathing of viruses that may be trapped and enriched
within the moisturised mask meshwork. Therefore, these conditions within masks are favourable for
pathogenic growth and are unfavourable for good/systemic microbiota i.e., individual specific. As a
result, the isolation of people with masks for extended periods can attain conditions for new and
individual specific strains formations/mutations of pathogens – to which other people in the
environment will be susceptible and/or not immune. Additionally, the high concentration of
microbiome in masks can be a potential source of infection for the population. The findings of
Fögen 2022 5 using data from the USA which shows that mask use correlates with an increased
mortality could be due to these processes. This phenomenon could also explain the similar figures
found by Spira 10 in the EU.
Compensatory physiological mechanisms
Our meta-analytically quantified CO2-rise and O2-depletion (Figure 2, 9A) with mask use certainly
needs physiological compensations (Figures 3, 4 and 10). Interestingly, the compensatory responses
to mask wearing (e.g., rise in heart rate, changes in respiratory rate and/or minute ventilation etc.)
was lower (absent or even reverse) than expected 115,131,132. In former human experiments with low
level 1-2% CO2 exposure to breathing air – which corresponds to measured values during mask use
133 – an increased respiratory minute volume (VE) of >34% was detected 115. In contrast to that and
according to our results under masks a significantly decreased VE by -19% on an average and up to -
24% under N95 masks occurs despite face mask driven CO2 exposure 133. Even the VE differed by
10% between N95 and surgical masks (Figure 3A). However, it appears to have no acute clinical
impact in the short term and does not exceed normal values of SpO2 and systemic CO2 although
these may become problematic in the long run. A compensatory higher arterial PaCO2 and
bicarbonate levels execute the buffering of inhaled CO2. Interestingly, during chronic breathing of
low CO2 concentrations (in the no-mask condition), due to compensatory mechanisms, e.g. lowered
blood pH, increased respiratory rate and VE 115 and an acclimatisation occurs 115,131,132,134,135. In mask
users, those compensatory mechanisms however seem to differ or get disturbed (e.g. no rise in
respiratory rate, heart rate and simultaneous fall in VE). Health risks should be considered despite
the mask related compensation attempts 133. During face mask use a rise in the arterial PaCO2 is
possible in the long term 20,52,58,60,98. Although, PaCO2 generally remains at a sub-threshold level in
Consequences of wearing face masks
healthy mask users 98,131, concerning pathological changes can occur in older (>60 years) and sick
people 20,59.
Our findings depicted an absence of typical compensatory reactions to transient hypercarbia thereby
implying a suppression of a physiological response owing to the unusual conditions of wearing a
mask. The reasons behind this phenomenon, i.e. the absence of a rise in the respiratory rate and
ventilation, remain unclear. The simultaneous change in the adverse direction (CO2 rise and
simultaneous O2 fall with concomitant dead space- and resistance enlargement caused by the mask)
may be responsible for this. The drop in SpO2 and the rise in CO2 (PtCO2, ETCO2, PaCO2) with no
major changes in the heart rate in our meta-analysis also transpires to be an unexpected reaction.
Sukul et al 20 reported altered breathing patterns, respiratory resistance and discomfort under
medical masks. Adults younger than 60 years of age described slow breathing (slow and deep
inspiration and expiration) under masks, whereas shallow/thoracic breathing (breathing with
increased inhalation duration and effort), respiratory resistance and dyspnoea was portrayed by
those ≥ 60 years of age. Fittingly, altered breathing patterns/kinetics, progressive changes towards
deoxygenation, hypercarbia and insignificant changes in the respiratory and heart rate transpired to
be surprising mask outcomes in our present results (hypercapnia-like effects). Thus, prolonged
masks use may lead to hypercapnic hypoxia like conditions. While short and acute hypercapnic
hypoxia like conditions in healthy individuals can promote positive effects (sport, training etc.), a
chronic/prolonged hypercapnic hypoxia (as known from sleep apnoea) is toxic for the
cardiovascular system in the long run – causing metabolic syndrome 8 as well as additional effects
on cognitive functions 136.
N95 mask compared to surgical mask
In line with recent findings by Kisielinski 2021 8 and Sukul 2022 20, the present results clearly show
that N95 masks lead to significantly more pronounced and unfavourable biochemical, physiological
and psychological effects (Figure 7) than surgical masks. Altogether, the results in blood
oxygenation, discomfort, heart rate, CO2, exertion, humidity, blood pressure, VE, temperature,
dyspnoea and itching etc. can be attributed to the larger (almost doubled) dead space and higher
breathing resistance of the N95 mask 8. Compared to the surgical mask upon the short-term effects,
N95 masks could impose elevated health risks under extended use. Interestingly, recent data from a
large multi-country RCT study show no significant differences between the two mask types in terms
of SARS-CoV2 infection rates 137.
Short mask experiment times
It is noteworthy to say that in studies with short assessment times neither correspond to real-life
conditions nor do they exclude short-term compensatory mechanisms, e.g. obvious for CO2-
rebreathing. However, immediate compensatory mechanisms can hide further adverse reactions
115,131,133. Therefore, longer observation times can lead to clearer values that are closer or above the
thresholds due to the attenuation or collapse of transient physiological mechanisms. The
experimental studies used here examined important outcomes only had a median examination time
of 18 minutes (Figure 11). Heterogeneous studies with small sample sizes yielded significant and
medium to strong results (Figures 10 and 12). Nevertheless, experimental studies with longer
assessment periods are needed.
The observational studies included in the present analysis on symptoms were conducted over
significantly longer periods (median 240 min, IQR 180) and are able to consider cumulative and
long-term effects. It is known that observational studies are far more precise in finding negative
effects and are particularly suitable to investigate exposures (e.g., air pollution or smoking) that are
difficult or impossible to investigate in randomised controlled trials (RCTs). In addition,
Consequences of wearing face masks
observational studies are important to investigate causes with a long latency period, such as
toxicological and carcinogenic effects from environmental exposures or drugs 42.
The longest period of included studies was 8 months with an averaged of wearing the mask 8 hours
per day (observational study), however with the shortest study with a 5 minutes
examining/exposition time (controlled trail).
Possible sub-threshold impact of masks –the low-dose long-term effect on health
In contrast to our study, most of the recent systematic reviews 21–25 have only analysed a few
outcome threshold values without considering comprehensive effects, exposure time and the
susceptibility of the exposed organisms and tissues. Therefore, their recommendations e.g. masks
are harmless and safe for everybody etc. appears to be superficial, non-medical, non-holistic and
misleading.
In accordance with conclusions of Fikenzer, Sukul and Zhang 20,45,64, we have found hints to
deleterious effects even without exceeding physiological threshold values and we have interpreted
these data as a risk for individuals with suppressed compensatory mechanisms such as in elderly
and sick subjects with cardiorespiratory diseases, infection, diabetes, cancer and other
comorbidities. Sukul et al 20 were able to show that the unfavourable effects are more pronounced in
the elderly (aged: 60 – 80 years). Moreover, they could provide evidence for toxic effects of face
masks including oxidative stress, immunosuppression, deoxygenation and hypercarbia induced
vasoconstriction and altered systemic microbial activity. Even with CO2 and SpO2 levels that do not
exceed the limits, many clinical researchers have also found troubling results in face mask wearers.
Neurologists observed changes in MRI brain signal baseline level due to face mask use 9. Wearing a
surgical mask for merely 9 minutes increased end-tidal CO2 causing mild hypercapnia. This was
responsible for a compensatory increase in cerebral blood flow with morphological changes similar
to that of a CO2 gas challenge or holding your breath. In patients with aneurysms or brain tumours
this phenomenon could be deleterious. Another study showed a pathologic and altered brain
metabolism while wearing a N95 mask for 6 hours 11. The MRI imaging revealed a significant drop
in brain oxygenation. A more than 50% drop in oxygenation in the cingulate gyrus (cognition
circuit) after 6 hours of mask use was associated with clinical symptoms of a confused state in 80%
of the subjects above 35 years. The authors even concluded that the general population should not
wear a N95 mask. This phenomenon of brain deoxygenation could be dangerous for people with
altered brain functions when on medication, after a transient ischaemic attack (TIA) or stroke
respectively.
Ophthalmological studies indicated risk of retinal damage from long-term use of masks. N95 masks
reduced the vascular density in the vascular plexus even under resting conditions as early as after 60
minutes 138. Here, the drop in SpO2 and increase in blood pressure were significant but within the
normal physiological range. Another study reported a significant mask-induced increase in
intraocular pressure (IOP) after approx. 5 minutes of wearing 6. Thus, wearing masks may
counteract the therapy aiming to reduce the IOP and can exacerbate irreversible long-term vision
problems in individuals with glaucoma. Numerous other studies have shown that the long-term
effects, leading to deleterious clinical outcome may result from prolonged mask wearing 9,11,138,139.
Such effects are comparable to sick building syndrome (SBS) 140, cigarette smoking and other
chronic, slightly toxic influences relevant to the general population.
In accordance with our present analysis and precedent scoping review 8, mask-related changes in
leaning towards pathological values can lead to illness and clinical consequences, just like
chronically, repeated subliminal harmful environmental events. Occupational diseases defined by
the International Labour organization (ILO) and that are in accordance with the worker´s
compensation act in Germany illustrates the potential harm caused by chronic exposure to
subthreshold environmental factors 141. Numerous examples of these principles can be found in the
literature concerning pharmacology, toxicology, clinical and occupational medicine and even in
Consequences of wearing face masks
psychology 142–151. Many other toxicological and environmental health examples are presented in the
recent scoping review by Kisielinski et al 8, which refers to MIES (Mask-Induced Exhaustion
Syndrome). Such subliminal chronical changes and harmful effects in the long run are comparable
to the sick building syndrome (SBS) 140, cigarette smoking 152, salty diet 153, aluminium
environmental pollution 154, low-level lead exposure 155, organochlorine pesticides and
polychlorinated biphenyl exposure 156 or even the so-called climate change exposure 157.
Altogether, even the subliminal changes due to face mask use can become clinically relevant.
Overlapping of face mask effects (MIES) with long-COVID symptoms
Regarding the numerous mask symptoms an important question arises: Can masks be responsible
for a misinterpreted long-COVID-syndrome after an effectively treated COVID-19 infection?
Nearly 40% of main long-COVID symptoms 158 overlap with mask related complaints and
symptoms described by Kisielinski et al as MIES 8 like fatigue, dyspnoea, confusion, anxiety,
depression, tachycardia, dizziness, headache, which we also detected in the qualitative and
quantitative analysis of face mask effects in our systematic review. It is possible that some
symptoms attributed to long-COVID are predominantly mask-related. Further research on this
phenomenon needs to be conducted.
Complaints and symptoms under mask use and the WHO definition of health
Amongst the perceived sensations with mask use only 6 symptoms (exertion, discomfort, shortness
of breath, humidity, heat and itch) could be meta-analysed and have resulted in predominantly
strong effect sizes (Figure 12). In the pooled prevalence analysis, we included eight main symptoms
namely headache, acne, skin irritation, shortness of breath, heat, itch, voice disorder and dizziness
(Figure 13) out of which all were significant in the evaluated population (Figure 8). There are many
more reported in the literature. However, these could not be meta-analysed due to the low number
of comparable studies on those particular complaints. In the included literature additional reported
mask related symptoms were: rhinitis 80, disabilities to think and to concentrate 58,61,68,78, drowsiness
78, communication disorder 61,88,89, depression and mood swings 72,88,90,91, anger 72, perceived
discomfort 41,45,52,73, anxiety 72,88,91, and an overall perceived fatigue and exhaustion 44,45,47,48,52,53,55,56,61–
64,66,69,70,86.
All of these mask-related symptoms contradict a state of well-being and health as defined by the
WHO. According to the WHO; “health is a state of complete physical, mental and social well-being
and not merely the absence of disease or infirmity” 159. Based on the facts we have found, the use of
face mask in the hope of maintaining health is unfortunately contradicting the WHO's definition of
health. Regarding all the possible side effects of mask and their still unproven efficacy against viral
transmission within the general population 4,160–162, health seems not to be substantially preserved by
wearing face masks. So far, only two randomized controlled mask trials for prevention of SARS-
CoV-2 infection in the general population have been published: one high quality study from
Denmark, Europe 163, and the other from Bangladesh with biased results and a lot of inconsistencies
164. Based on a Bayesian random-effects meta-analysis of these two trials, the posterior median for
relative risk was 0.91 (95% credible interval 0.63 to 1.33, 73% probability of some benefits with
very limited evidence) 165. The paucity in high-quality mask studies is unfortunate. Seeing the
overall weak evidence for efficacy of masks against viral transmission within the general population
4,160–162,166–168, face masks have to be evaluated appropriately in the sense of the Hippocratic Oath and
as per the Primum nihil nocere (above all do not harm). To avoid at all costs that the damage caused
by preventive or therapeutic measures becomes greater than that caused by the disease itself, should
be the credo of all those involved in the containment of the crisis, including politicians and the so-
called experts. Medical decisions can only be made on the basis of comprehensive knowledge on a
patient's overall condition, individualised case history, considering all previous illnesses and
Consequences of wearing face masks
interventions, physical and mental predispositions and his/her socio-economic state etc. When it
comes to medical decision-making in a sick person, the weighing of therapeutic measures for the
benefit of the patient against the side effects of the therapy is to be evaluated differently than a
prophylactic procedure in healthy people. If wrong decisions are made in the selection of preventive
measures in healthy individuals, or if they are improperly applied, the consequences are usually
much more severe and liability claims are often unavoidable. From a standardisation point of view
the filtration efficacy of mask for viruses remains hypothetic and not in line with the established
standards. There are national and international standards for bacteria filtration efficiency (BFE) for
medical masks since decades, for example the EU-EN 14683, or the USA-ASTM F2101. They are
the prerequisites for general approval. However, since 2020 (i.e. nearly 3 years), no comparable
standard/testing of masks for viruses does yet exist. Given the fact, that medical masks (surgical and
N95) increase particle exhalation in the smallest size range of 0.3 – 0.5 µm, shifting the geometric
mean diameter toward smaller sizes (longer in air) compared to no mask conditions 169 doubts arise.
Such scientific facts are pointing towards the nebulisation effect of masks, which could be an add-
on for their weakness against viral transmission in general.
Limitations
While looking at the potential limitations our systematic review rarely discussed the inhaled toxins
associated with the mask. Inhalation and ingestion of toxic substances, which are ingredients of the
masks, are also of importance in evaluating this pandemic non-pharmaceutical intervention (NPI).
In addition, our work has not extensively studied the microbial colonisation of masks and the
consequences of contamination by microorganisms for the wearer.
Based on the studies conducted during the pandemic, the control groups without masks were mostly
the same individuals, or individuals who were not mask abstinent for too long (general mask
requirement)170, so the mask-no-mask differences may be mitigated.
Because of the rapid flow of science, new interesting papers have certainly appeared that we were
unable to consider in the meta-analysis as they appeared after the period of our data search (search
limitation to 31.12.2021). The most important and relevant observational studies were considered
for this analysis thereby addressing the physio-metabolic and clinical effects. Numerous
psychological and other effects could not be assessed analytically as too few relevant and evaluable
studies were available.
Conclusion
This systematic review comprehensively revealed ample evidence for multiple adverse physio-
metabolic and clinical outcomes of medical face masks. This can have long-term clinical
consequences, especially for vulnerable groups e.g. children, pregnant, elderly and ill. The N95
masks lead to measurably more adverse results than surgical masks. Besides transient and
progressive hypoxaemia, hypercarbia and individualised clinical symptoms our findings are in line
with reports on face masks driven down-stream aberrations (e.g. oxidative stress, hypercapnia,
vasoconstriction, pro-inflammatory response, immunosuppression etc.) at the organ, cellular and
microbiome levels and support the MIES (Mask Induced Exhaustion Syndrome). From our point of
view, while a short application of the mask seems to be less harmful, longer and long-term use may
cause subliminal shift of values towards the pathophysiological direction.
So far, several MIES symptoms may have been misinterpreted as long COVID symptoms.
In any case, the possible MIES triggered by masks contrasts with the WHO definition of health.
The exact threshold of harmless and non-pathogenic time wearing a mask should exclusively be
determined by further intensive research and studies. Due to the ultimate lack of exclusion of the
harmfulness of mask wearing, mask use by the general public should be discouraged.
Consequences of wearing face masks
From the above facts, we conclude that a mask requirement must be reconsidered in a strictly
scientific way without any political interference as well as from a humanitarian and ethical point of
view. There is an urgent need to balance adverse mask effects with their anticipated efficacy against
viral transmission.
Acknowledgements: We thank Mrs. Bonita Blankart for proofreading the manuscript.
Author Contributions: Conceptualization, K.K., A.S. and O.H. ; Methodology, K.K., A.S. and
O.H.; Software, K.K., O.H.; Formal analysis, K.K., O.H. S.W., B.W., S.F., A.P., B.K., S.K.M., P.S.
and A.S.; Investigation, K.K., O.H., S.W., B.W., P.S. and A.S.; Physio-metabolic and clinical
interpretations, K.K., S.W., S.F., B.K., A.P., P.S. and A.S.; Writing—original draft preparation, K.K.,
O.H., P.S. and A.S.; Writing—review and editing, K.K., O.H., S.W., B.W., S.F., A.P., B.K., P.S.,
S.K.M. and A.S.. All authors have read and agreed to the published version of the manuscript
Correspondence and requests should be addressed to K.K. and P.S..
Conflict of Interest: The authors declare no conflict of interest.
Funding: This research received no external funding.
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Figures 1-13:
Figure 1. PRISMA flow chart of the systematic review. From initial 2168, fifty-four studies were later
included in the qualitative synthesis. Finally 37 studies were evaluated statistically in the meta-analysis
(quantitative analysis).
Consequences of wearing face masks
Figure 2.
Forest (left) and Funnel
plots (right) of meta-
analysis of blood
oxygenation and blood
carbon dioxide outcomes
while wearing a face
mask. All face mask types
are initially considered
together, later subgroups
(surgical and N95) are
evaluated. If studies
examine two different
mask types in parallel, the
corresponding studies are
marked: □=surgical mask
=N95 mask.
A: Blood oxygen is
significantly lowered in
mask use. In the subgroup
analysis this could also be
found for N95 mask use.
From the pooled analysis,
it seems, that N95 mask
may be responsible for a
larger SpO2 drop than
surgical masks. In studies
evaluating both conditions
(surgical and N95 mask)
the N95 mask yielded
always lower O2-values
than the surgical masks.
B: In the pooled analysis,
blood carbon dioxide
(PtCO2, ETCO2, PaCO2)
is significantly elevated in
mask use. This could be
found for general mask
use and in the subgroup
analysis for surgical
mask, and also for N95
mask use. In studies
evaluating both conditions
(surgical and N95 mask)
the N95 mask yielded
always higher CO2-values
than the surgical masks.
Consequences of wearing face masks
Figure 3. Forest (left) and Funnel plots (right) of meta-analysis of physiological respiratory
outcomes while wearing a face mask. A shows results for ventilation (VE), B for respiratory rate
(RR). All face mask types are initially considered together, later subgroups (surgical and N95) are
evaluated. If studies examine two different mask types in parallel, the corresponding studies are
marked: □=surgical mask ■=N95 mask.
A: Breathing volume is significantly lowered in mask use in the pooled analysis. This could be
found for general, for surgical, and N95 mask use. In studies evaluating both conditions (surgical
and N95 mask) the N95 mask yielded always lower ventilation (VE) than the surgical masks.
B: No statistical difference could be found regarding respiratory rate in mask use in the pooled
analysis, even in the subgroup analysis (not shown).
Consequences of wearing face masks
Figure 4. Forest (left) and Funnel plots (right) of metaanalysis of the physiological cardiovascular
outcomes systolic blood pressure (SBP) and heart rate (HR). All controlled intervention studies in
which measurements were taken during physical activity with face masks were included (exclusion
of rest situation and pre-post studies). All face masks types are initially considered together, later if
possible subgroups (surgical and N95) are evaluated. If studies evaluate two different mask types in
parallel, the corresponding studies are marked: □=surgical mask ■=N95 mask.
A: Systolic blood pressure is elevated in the mask condition and also for the subgroup of surgical
mask. In studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded always
higher SBP than the surgical mask, however this effect was not statistically significant.
B: For the N95 mask condition a low significance for a slight increase in heart rate could be found.
In studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded always higher
HR than the surgical mask, and this effect was statistically significant.
Consequences of wearing face masks
Figure 5. Forest (left) and Funnel plots (right) of meta-analysis of physical outcomes while wearing
a face mask. A shows results for temperature of skin, B for air humidity underneath the face mask.
All mask types are initially considered together, later subgroups (surgical and N95) are evaluated. If
studies examine two different mask types in parallel, the corresponding studies are marked:
□=surgical mask ■=N95 mask.
A: Skin covered by mask has a significantly higher temperature during rest and activity. This could
be found for general mask use and for N95 mask use but not for surgical mask use. In studies
evaluating both conditions (surgical and N95 mask) the N95 mask yielded higher temperatures than
the surgical mask, but this could not be analised further due to lack of further studies comparing
both conditions.
B: The dead space covered by mask has a significantly higher air humidity in the pooled analysis.
Consequences of wearing face masks
Figure 6. Forest and Funnel plots of meta-analysis of measured discomfort (A), itch (B), exertion
(C), shortness of breath (D), perceived heat (E) and humidity (F) during face mask use (VAS,
Likert-scales or similar). All face mask types are initially considered together, later subgroups
(surgical and N95) are evaluated. If studies examine two different mask types in parallel, the
corresponding studies are marked: □=surgical mask ■=N95 mask.
A: Perceived discomfort is significantly higher in face mask use in the pooled analysis. This could
be found for general mask use, in the subgroup analysis for surgical-, and for N95 mask use. A
pooled analysis comparing both conditions (surgical mask and N95 mask) resulted in statistically
significant higher discomfort rates for the N95 mask than the surgical mask.
B: An overall significancy for itching could be found for mask use. Also in N95 mask use the
perceived itching was statistically significantly elevated according to the pooled subgroup analysis.
C: In studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded always
higher exertion rates than the surgical masks.
D: Perceived shortness of breath is significantly higher in mask use in the pooled analysis.
E: Perceived heat is significantly higher in the pooled analysis.
F: Perceived humidity is significantly higher in mask use. The subgroup analysis revealed a
statistical significancy for an increase in humidity perception using a surgical mask. In studies
evaluating both conditions (surgical and N95 mask) the N95 mask yielded always higher humidity
perception rates than the surgical mask. A pooled analysis resulted in a statistical significance for
higher humidity perception in N95 masks than surgical masks.
Consequences of wearing face masks
Figure 7.
Results comparing
the N95 to the
surgical mask in the
meta-analysis.
Forest (left) and
Funnel plots (right)
of meta-analysis of
diverse outcomes
while wearing a
N95 mask vs
surgical mask are
shown. A depicts
the biochemical, B
the cardirespiratory
outcomes and C the
subjective
sensations
outcomes.
N95 mask leads to
measurably less
favourable results
compared to the
surgical mask,
significantly for
oxygenation
(decrease), heart
rate (increase),
discomofort and
humidity (both
increases). This
trend was also
evident for minute
volume (decrease),
CO2 and systolic
blood pressure (both
increases), but in
those comparisons
not statistically
significant due to
too few includable
studies.
Consequences of wearing face masks
Figure 8. Forest (left) and Funnel plots (right) of meta-analysis of pooled symptom prevalence
while wearing a face mask. Headache (62%), acne (38%), skin irritation (36%), shortness of breath
(33%), heat (26%), itch (26%), voice disorder (23%) and dizziness (5%) while wearing a mask are
significant in the evaluated population (n=8128) .
Consequences of wearing face masks
Figure 9. Summary of pooled metaanalytic evaluation of biochemical (A) and physical effects (B)
during face mask use. The height of the bars reflects the SMD (standard mean difference), their
error bars correspond to the confidence intervals.
A: For carbon dioxide rise in the blood there is a medium effect size of >0.5 and for oxygen drop a
small effect size of >0.2 regarding the standard mean difference values thresholds according to
Cohen 1988.
B: For elevated Humidity and Temperature rise under the face mask there is a strong effect size of
≥0.8.
The metaanalytical statistical data were as follows:
Oxygen (SpO2): SMD -0.24, 95% CI -0.38 to -0.11, Z=3.53, p=0.0004;
Carbon dioxide (PtCO2, ETCO2,PaCO2): SMD +0.64, 95% CI 0.31 to 0.96, Z=3.86, p=0.0001;
Humidity: SMD +2.24, 95% CI 1.32 to 3.17), Z=4.75, p<0.00001;
Temperature: SMD +0.8, 95% CI 0.23 to 1.38, Z=2.72, p=0.008.
Consequences of wearing face masks
Figure 10. Summary of pooled metaanalytic evaluation of cardiorespiratory effects during face
mask use. The height of the bars reflects the SMD (standard mean difference), their error bars
correspond to the confidence intervals.
Clear effects for a decrease in ventilation and tidal volume are illustrated, no effect for respiratory
rate and weak to low effect for increase in heart rate and systolic blood pressure. For ventilation
there is a medium effect size of >0.5 with a small effect size of >0.2 for tidal volume of the
standard mean difference values according to Cohen 1988.
The meatanalytical statistical data were as follows:
Ventilation: SMD -0.72, 95% CI -0.99 to -0.46, Z=5.36, p<0.00001;
Tidal volume: SMD -0.37, 95% CI -0.63 to -0.11, Z=2.82, p=0.005;
Respiratory rate: SMD +0.01, 95% CI -0.29 to 0.30, Z=0.08, p=0.94;
Heart rate: SMD +0.11, 95% CI -0.05 to 0.28, Z=1.34, p=0.18;
Sytolic blood pressure: SMD +0.17, 95% CI 0.03 to 0.32, Z=2.39, p=0.02.
Consequences of wearing face masks
Figure 11. IIlustration of the duration of studies in which measurements were made on mask effects
(physical, biochemical, and physiological) in 934 participants. The median is 18 minutes (yellow
dotted line) with an interquartile range of 50 . The study with the longest experimental duration
included 21 subjects, corresponding to 2.2% of the total population studied. Striking not only is a
very short trial time compared to the everyday scenarios workday and school attendance (see
interrrupted, auxiliary lines in blue and red), but also a strongly deviating mask exposure duration
with outliers (mean of 45.8 minutes with standard deviation of 69.9). Therefore, the mean is not an
appropriate parameter to characterize this distribution.
Consequences of wearing face masks
Figure 12. Summary of pooled metaanalytic evaluation of face mask-wearing sensations measured
with standardised Borg-. Likert-, VAS-scales or similar. The height of the bars reflects the SMD
(standard mean difference), their error bars correspond to the confidence intervals.
Five out of 6 complaint categories (83%) are above the strong effect size threshold of >0.8 of the
standard mean difference values according to Cohen 1988.
The metanalytical statistical data were as follows (SMD=standard mean difference):
Itch: SMD +1.57, 95 %CI -0.08 to 3.23, Z=1.86, p=0.06;
Shortness of breath: SMD +1.46, 95% CI 0.42 to 2.50, Z=2.75, p=0.006;
Discomfort: SMD +1.16, 95% CI 0.58 to 1.73, Z=3.94, p<0.0001;
Exertion: SMD +0.9, 95 % CI 0.57 to 1.23, Z=5.31, p<0.00001;
Humidity: SMD +0.9, 95% CI 0.34 to 1.46, Z=3.17, p=0.002;
Heat: SMD +0.77, 95% CI 0.29 to 1.26, Z=3.11, p=0.002.
Consequences of wearing face masks
Figure 13. Representation of symptom prevalence in % during face mask use as the area of the
circles. Along the X-axis, the main recorded symptoms are listed. The higher the prevalence, the
bigger the circles and the more often the symptoms.
The Y-axis gives the probability of non-random occurrence of the symptoms and includes the
statistical Z-value. Thus, the higher the circles are arranged, the more robust is the relationship to
face mask wearing.
The meatanalytical statistical data were as follows:
Headache: 62% (95% CI 48-75%), Z=8.77, p<0.00001;
Acne: 38% (95% CI 22-54%), Z=4.58, p<0.00001:
Skin irritation: 36% (95% CI 24-49%), Z=5.61, p<0.00001;
Shortness of breath: 33% (95% CI 23-44%), Z=6.28, p<0.00001;
Heat: 28% (95% CI 15-0.37%), Z=4.72, p<0.00001;
Itch: 26% (95% CI 15-36%), Z=4.77, p<0.00001;
Voice disorder 23% (95% CI 2-43%), Z=2.15, p<0.03;
Dizziness 5% (95% CI 1-9%), Z=2.5, p=0.01.
Figures
Figure 1
PRISMA ow chart of the systematic review. From initial 2168, fty-four studies were later included in the
qualitative synthesis. Finally 37 studies were evaluated statistically in the meta-analysis (quantitative
analysis).
Figure 2
Forest (left) and Funnel plots (right) of meta-analysis of blood oxygenation and blood carbon dioxide
outcomes while wearing a face mask. All face mask types are initially considered together, later
subgroups (surgical and N95) are evaluated. If studies examine two different mask types in parallel, the
corresponding studies are marked: ฀=surgical mask ฀=N95 mask.
A: Blood oxygen is signicantly lowered in mask use. In the subgroup analysis this could also be found
for N95 mask use. From the pooled analysis, it seems, that N95 mask may be responsible for a larger
SpO2 drop than surgical masks. In studies evaluating both conditions (surgical and N95 mask) the N95
mask yielded always lower O2-values than the surgical masks.
B: In the pooled analysis, blood carbon dioxide (PtCO2, ETCO2, PaCO2) is signicantly elevated in mask
use. This could be found for general mask use and in the subgroup analysis for surgical mask, and also
for N95 mask use. In studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded
always higher CO2-values than the surgical masks.
Figure 3
Forest (left) and Funnel plots (right) of meta-analysis of physiological respiratory outcomes while
wearing a face mask. A shows results for ventilation (VE), B for respiratory rate (RR). All face mask types
are initially considered together, later subgroups (surgical and N95) are evaluated. If studies examine two
different mask types in parallel, the corresponding studies are marked: ฀=surgical mask ฀=N95 mask.
A: Breathing volume is signicantly lowered in mask use in the pooled analysis. This could be found for
general, for surgical, and N95 mask use. In studies evaluating both conditions (surgical and N95 mask)
the N95 mask yielded always lower ventilation (VE) than the surgical masks.
B: No statistical difference could be found regarding respiratory rate in mask use in the pooled analysis,
even in the subgroup analysis (not shown).
Figure 4
Forest (left) and Funnel plots (right) of metaanalysis of the physiological cardiovascular outcomes
systolic blood pressure (SBP) and heart rate (HR). All controlled intervention studies in which
measurements were taken during physical activity with face masks were included (exclusion of rest
situation and pre-post studies). All face masks types are initially considered together, later if possible
subgroups (surgical and N95) are evaluated. If studies evaluate two different mask types in parallel, the
corresponding studies are marked: ฀=surgical mask ฀=N95 mask.
A: Systolic blood pressure is elevated in the mask condition and also for the subgroup of surgical mask.
In studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded always higher SBP
than the surgical mask, however this effect was not statistically signicant.
B: For the N95 mask condition a low signicance for a slight increase in heart rate could be found. In
studies evaluating both conditions (surgical and N95 mask) the N95 mask yielded always higher HR than
the surgical mask, and this effect was statistically signicant.
Figure 5
Forest (left) and Funnel plots (right) of meta-analysis of physical outcomes while wearing a face mask. A
shows results for temperature of skin, B for air humidity underneath the face mask. All mask types are
initially considered together, later subgroups (surgical and N95) are evaluated. If studies examine two
different mask types in parallel, the corresponding studies are marked: ฀=surgical mask ฀=N95 mask.
A: Skin covered by mask has a signicantly higher temperature during rest and activity. This could be
found for general mask use and for N95 mask use but not for surgical mask use. In studies evaluating
both conditions (surgical and N95 mask) the N95 mask yielded higher temperatures than the surgical
mask, but this could not be analised further due to lack of further studies comparing both conditions.
B: The dead space covered by mask has a signicantly higher air humidity in the pooled analysis.
Figure 6
Forest and Funnel plots of meta-analysis of measured discomfort (A), itch (B), exertion (C), shortness of
breath (D), perceived heat (E) and humidity (F) during face mask use (VAS, Likert-scales or similar). All
face mask types are initially considered together, later subgroups (surgical and N95) are evaluated. If
studies examine two different mask types in parallel, the corresponding studies are marked: ฀=surgical
mask ฀=N95 mask.
A: Perceived discomfort is signicantly higher in face mask use in the pooled analysis. This could be
found for general mask use, in the subgroup analysis for surgical-, and for N95 mask use. A pooled
analysis comparing both conditions (surgical mask and N95 mask) resulted in statistically signicant
higher discomfort rates for the N95 mask than the surgical mask.
B: An overall signicancy for itching could be found for mask use. Also in N95 mask use the perceived
itching was statistically signicantly elevated according to the pooled subgroup analysis.
C: Perceived exertion is signicantly higher in mask use. In studies evaluating both conditions (surgical
and N95 mask) the N95 mask yielded always higher exertion rates than the surgical masks.
D: Perceived shortness of breath is signicantly higher in mask use in the pooled analysis.
E: Perceived heat is signicantly higher in the pooled analysis.
F: Perceived humidity is signicantly higher in mask use. The subgroup analysis revealed a statistical
signicancy for an increase in humidity perception using a surgical mask. In studies evaluating both
conditions (surgical and N95 mask) the N95 mask yielded always higher humidity perception rates than
the surgical mask. A pooled analysis resulted in a statistical signicance for higher humidity perception
in N95 masks than surgical masks.
Figure 7
Results comparing the N95 to the surgical mask in the meta-analysis. Forest (left) and Funnel plots
(right) of meta-analysis of diverse outcomes while wearing a N95 mask vs surgical mask are shown. A
depicts the biochemical, B the cardirespiratory outcomes and C the subjective sensations outcomes.
N95 mask leads to measurably less favourable results compared to the surgical mask, signicantly for
oxygenation (decrease), heart rate (increase), discomofort and humidity (both increases). This trend was
also evident for minute volume (decrease), CO2 and systolic blood pressure (both increases), but in those
comparisons not statistically signicant due to too few includable studies.
Figure 8
Forest (left) and Funnel plots (right) of meta-analysis of pooled symptom prevalence while wearing a
face mask. Headache (62%), acne (38%), skin irritation (36%), shortness of breath (33%), heat (26%), itch
(26%), voice disorder (23%) and dizziness (5%) while wearing a mask are signicant in the evaluated
population (n=8128).
Figure 9
Summary of pooled metaanalytic evaluation of biochemical (A) and physical effects (B) during face
mask use. The height of the bars reects the SMD (standard mean difference), their error bars correspond
to the condence intervals.
A: For carbon dioxide rise in the blood there is a medium effect size of >0.5 and for oxygen drop a small
effect size of >0.2 regarding the standard mean difference values thresholds according to Cohen 1988.
B: For elevated Humidity and Temperature rise under the face mask there is a strong effect size of 0.8.
The metaanalytical statistical data were as follows:
Oxygen (SpO2): SMD -0.24, 95% CI -0.38 to -0.11, Z=3.53, p=0.0004;
Carbon dioxide (PtCO2, ETCO2,PaCO2): SMD +0.64, 95% CI 0.31 to 0.96, Z=3.86, p=0.0001;
Humidity: SMD +2.24, 95% CI 1.32 to 3.17), Z=4.75, p<0.00001;
Temperature: SMD +0.8, 95% CI 0.23 to 1.38, Z=2.72, p=0.008.
Figure 10
Summary of pooled metaanalytic evaluation of cardiorespiratory effects during face mask use. The
height of the bars reects the SMD (standard mean difference), their error bars correspond to the
condence intervals.
Clear effects for a decrease in ventilation and tidal volume are illustrated, no effect for respiratory rate
and weak to low effect for increase in heart rate and systolic blood pressure. For ventilation there is a
medium effect size of >0.5 with a small effect size of >0.2 for tidal volume of the standard mean
difference values according to Cohen 1988.
The meatanalytical statistical data were as follows:
Ventilation: SMD -0.72, 95% CI -0.99 to -0.46, Z=5.36, p<0.00001;
Tidal volume: SMD -0.37, 95% CI -0.63 to -0.11, Z=2.82, p=0.005;
Respiratory rate: SMD +0.01, 95% CI -0.29 to 0.30, Z=0.08, p=0.94;
Heart rate: SMD +0.11, 95% CI -0.05 to 0.28, Z=1.34, p=0.18;
Sytolic blood pressure: SMD +0.17, 95% CI 0.03 to 0.32, Z=2.39, p=0.02.
Figure 11
IIlustration of the duration of studies in which measurements were made on mask effects (physical,
biochemical, and physiological) in 934 participants.
The median is 18 minutes (yellow dotted line) with an interquartile range of 50 . The study with the
longest experimental duration included 21 subjects, corresponding to 2.2% of the total population
studied.
Striking not only is a very short trial time compared to the everyday scenarios workday and school
attendance (see interrrupted, auxiliary lines in blue and red), but also a strongly deviating mask exposure
duration with outliers (mean of 45.8 minutes with standard deviation of 69.9). Therefore, the mean is not
an appropriate parameter to characterize this distribution.
Figure 12
Summary of pooled metaanalytic evaluation of face mask-wearing sensations measured with
standardised Borg-. Likert-, VAS-scales or similar. The height of the bars reects the SMD (standard mean
difference), their error bars correspond to the condence intervals.
Five out of 6 complaint categories (83%) are above the strong effect size threshold of >0.8 of the
standard mean difference values according to Cohen 1988.
The metanalytical statistical data were as follows (SMD=standard mean difference):
Itch: SMD +1.57, 95%CI -0.08 to 3.23, Z=1.86, p=0.06;
Shortness of breath: SMD +1.46, 95% CI 0.42 to 2.50, Z=2.75, p=0.006;
Discomfort: SMD +1.16, 95% CI 0.58 to 1.73, Z=3.94, p<0.0001;
Exertion: SMD +0.9, 95% CI 0.57 to 1.23, Z=5.31, p<0.00001;
Humidity: SMD +0.9, 95% CI 0.34 to 1.46, Z=3.17, p=0.002;
Heat: SMD +0.77, 95% CI 0.29 to 1.26, Z=3.11, p=0.002.
Figure 13
Representation of symptom prevalence in % during face mask use as the area of the circles. Along the X-
axis, the main recorded symptoms are listed. The higher the prevalence, the bigger the circles and the
more often the symptoms.
The Y-axis gives the probability of non-random occurrence of the symptoms and includes the statistical
Z-value. Thus, the higher the circles are arranged, the more robust is the relationship to face mask
wearing.
The meatanalytical statistical data were as follows:
Headache: 62% (95% CI 48-75%), Z=8.77, p<0.00001;
Acne: 38% (95% CI 22-54%), Z=4.58, p<0.00001:
Skin irritation: 36% (95% CI 24-49%), Z=5.61, p<0.00001;
Shortness of breath: 33% (95% CI 23-44%), Z=6.28, p<0.00001;
Heat: 28% (95% CI 15-0.37%), Z=4.72, p<0.00001;
Itch: 26% (95% CI 15-36%), Z=4.77, p<0.00001;
Voice disorder 23% (95% CI 2-43%), Z=2.15, p<0.03;
Dizziness 5% (95% CI 1-9%), Z=2.5, p=0.01.
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Prolonged daily face mask wearing over several months might affect health of the ocular surface and is reported to be associated with complaints of discomfort and dry-eye-like symptoms. We studied the ocular surface clinical parameters, tear soluble factors and immune cell proportions in ophthalmologists practicing within similar environmental conditions (n = 17) at two time points: pre-face-mask period (Pre-FM; end of 2019) and post-face-mask-wearing period (Post-FM; during 2020 COVID-19 pandemic), with continuous (~8 h/day) mask wear. A significant increase in ocular surface disease index (OSDI) scores without changes in tear breakup time (TBUT), Schirmer’s test 1 (ST1) and objective scatter index (OSI) was observed Post-FM. Tear soluble factors (increased—IL-1β, IL-33, IFNβ, NGF, BDNF, LIF and TSLP; decreased—IL-12, IL-13, HGF and VEGF-A) and mucins (MUC5AC) were significantly altered Post-FM. Ex vivo, human donor and corneoscleral explant cultures under elevated CO2 stress revealed that the molecular profile, particularly mucin expression, was similar to the Post-FM tear molecular profile, suggesting hypercapnia is a potential contributor to ocular surface discomfort. Among the immune cell subsets determined from ocular surface wash samples, significantly higher proportions of leukocytes and natural killer T cells were observed in Post-FM compared to Pre-FM. Therefore, it is important to note that the clinical parameters, tear film quality, tear molecular factors and immune cells profile observed in prolonged mask-wear-associated ocular surface discomfort were distinct from dry eye disease or other common ocular surface conditions. These observations are important for differential diagnosis as well as selection of appropriate ocular surface treatment in such subjects.
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Background: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. Design: Multicenter, randomized, noninferiority trial. (ClinicalTrials.gov: NCT04296643). Setting: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. Participants: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19. Intervention: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site. Measurements: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test. Results: In the intention-to-treat analysis, RT-PCR-confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]). An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR-confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada (HR, 2.83 [CI, 0.75 to 10.72]), 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel (HR, 1.54 [CI, 0.43 to 5.49]), 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan (HR, 1.50 [CI, 0.25 to 8.98]), and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt (HR, 0.95 [CI, 0.60 to 1.50]). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group. Limitation: Potential acquisition of SARS-CoV-2 through household and community exposure, heterogeneity between countries, uncertainty in the estimates of effect, differences in self-reported adherence, differences in baseline antibodies, and between-country differences in circulating variants and vaccination. Conclusion: Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of RT-PCR-confirmed COVID-19 for medical masks when compared with HRs of RT-PCR-confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity. Primary funding source: Canadian Institutes of Health Research, World Health Organization, and Juravinski Research Institute.
Article
Objective To assess the effectiveness of mandatory use of face covering masks (FCMs) in schools during the first term of the 2021–2022 academic year. Design A retrospective population-based study. Setting Schools in Catalonia (Spain). Population 599 314 children aged 3–11 years attending preschool (3–5 years, without FCM mandate) and primary education (6–11 years, with FCM mandate). Study period From 13 September to 22 December 2021 (before Omicron variant). Interventions A quasi-experimental comparison between children in the last grade of preschool (5 years old), as a control group, and children in year 1 of primary education (6 years old), as an interventional group. Main outcome measures Incidence of SARS-CoV-2, secondary attack rates (SARs) and effective reproductive number (R*). Results SARS-CoV-2 incidence was significantly lower in preschool than in primary education, and an increasing trend with age was observed. Six-year-old children showed higher incidence than 5 year olds (3.54% vs 3.1%; OR 1.15 (95% CI 1.08 to 1.22)) and slightly lower but not statistically significant SAR (4.36% vs 4.59%; incidence risk ratio 0.96 (95% CI 0.82 to 1.11)) and R* (0.9 vs 0.93; OR 0.96 (95% CI 0.87 to 1.09)). Results remained consistent using a regression discontinuity design and linear regression extrapolation approaches. Conclusions We found no significant differences in SARS-CoV-2 transmission due to FCM mandates in Catalonian schools. Instead, age was the most important factor in explaining the transmission risk for children attending school.
Article
Context Use of facemasks in sport has been a particularly complex issue during the COVID-19 pandemic. Objectives A systematic review to examine the physiological effects the different types of masks have on healthy adults when doing physical exercise. Data sources PubMed, SPORTDiscus, Scopus, and Litcovid were searched up to March 20, 2021, following the PRISMA model. Articles published in the last 5 years with healthy adults. Study Selection A total of 633 studies related to the use of masks during physical exercise were found, of which 8 articles met the criteria to be included. Study Design Systematic review. Level of Evidence Level 2. Data Extraction The search process and the review of the articles were carried out by independent expert researchers. The risk of bias and the methodological quality of the different studies included in the systematic review were calculated following the Cochrane criteria using an adaptation for random cross-studies. Once the information was properly structured, the results were extracted, and the findings of the study analyzed. Results There were significant changes in the following physiological variables when engaging in physical exercise using masks: 25% in the heart rate and dyspnea, 37.5% in the rating of perceived exertion, 50% in the pulmonary variables, and 37.5% in discomfort. The oxygen saturation, blood pressure, systolic blood pressure, diastolic blood pressure, and the concentration of blood lactate did not present any significant effect in this study. Conclusions The usage of masks by a healthy adult population during the performance of physical exercise has shown minimal effects with regard to physiological, cardiorespiratory, and perceived responses. Some symptoms can be dyspnea, effort perceived, or discomfort, among others. These findings indicate that the use of masks is not harmful to individuals’ health. It does not present any significant detrimental effect on physical performance or risk to their well-being. However, further experiments are required to corroborate the findings of this review.