BRIEF REPORT Cerebral and systemic physiological effects of wearing face masks in young adults Jonas B. Fischera,1, Lisa Kobayashi Friska,1, Felix Scholkmannb, Raquel Delgado-Mederosc, Mercedes Mayosd,e, and Turgut Durdurana,f,2 a ICFO - Institut de Ciències Fotòniques, Barcelona Institute of Science and Technology, Castelldefels (Barcelona) 08860, Spain; bBiomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland; cSant Pau Biomedical Research Institute, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain; dSleep Unit, Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain; eCentro de Investigación Biomédica en Red (CIBER) Enfermedades Respiratorias (CB06/06), Madrid 28029, Spain; and fInstitució Catalana de Recerca i Estudis Avançats, Barcelona 08010, Spain Edited by Marcus E. Raichle, Washington University in St. Louis, St. Louis, MO, and approved September 3, 2021 (received for review May 21, 2021) The COVID-19 pandemic led to widespread mandates requiring the custom near-infrared spectroscopies and commercial physiological wearing of face masks, which led to debates on their benefits and monitors in healthy young adults. possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have inves- Results tigated the effect of commonly available face masks (FFP2 and Thirteen volunteers (median age: 27.0 y [23 to 33 y], six females) surgical) on cerebral hemodynamics and oxygenation, particularly took part in the study. Fig. 1 summarizes the findings. Small but microvascular cerebral blood flow (CBF) and blood/tissue oxygen significant changes in cerebral blood flow (CBF) and cerebral saturation (StO2), measured by transcranial hybrid near-infrared blood oxygen saturation (StO2) were detected for both mask spectroscopies and on systemic physiology in 13 healthy adults APPLIED PHYSICAL types: 1) CBF increased by 6.5% (95% CI: 2.6, 10.5%) for the (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these FFP2 mask and 6.2% (95% CI: 2.4, 9.9%) for the surgical mask; 2) StO2 increased by 0.9% (95% CI: 0.2, 1.7%) for the FFP2 SCIENCES changes are comparable to those of daily life activities. This plat- form and the protocol provides the basis for large or targeted mask and also 0.9% (95% CI: 0.1, 1.6%) for the surgical mask; 3) studies of the effects of mask wearing in different populations total hemoglobin concentration (tHb) increased significantly and while performing critical tasks. only for the FFP2 mask by 0.9 μM (95% CI: 0.3, 1.5 μM). Changes in oxygen extraction fraction (OEF) and cerebral | | face masks cerebral hemodynamics systemic physiology | Downloaded from https://www.pnas.org by 158.109.91.150 on December 14, 2022 from IP address 158.109.91.150. metabolism (CMRO2) (defined in SI Appendix) were not statistically | COVID-19 near-infrared spectroscopy significant: 1) OEF decreased by −1.7% (85% CI: −4.1, 0.8) for PHYSIOLOGY the FFP2 mask and by −2.4% (95% CI: −4.7, 0.0) for the surgical M any governments have mandated the wearing of face masks in response to the coronavirus disease 2019 (COVID-19) pandemic in order to mitigate the acute respiratory syndrome mask; 2) CMRO2 increased by 4.5% (95% CI: −1.3, 10.4%) for the FFP2 mask and by 3.6% (95% CI: −1.7, 9.0%) for the surgical mask. None of these changes were statistically significantly dif- coronavirus 2 (SARS-CoV-2) transmission. The effectiveness of ferent between the two mask types. this measure is currently being evaluated (1). This has led to on- EtCO2 showed a significant change but was discarded since the going discussions about possible adverse effects of mask wearing probe was affected by the air trapped within the mask. Transcu- (e.g., dizziness, headaches, fainting), especially within the elderly, taneous carbon dioxide partial pressure (TcCO2) and SpO2 did during long-term continuous mask usage and during physical ac- tivity. Chan et al. (2) reported that the arterial oxygenation (SpO2) not significantly change due to wearing a mask, while mean ar- did not change in elderly subjects after 1 h, while Law et al. (3) terial pressure (MAP) and heart rate (HR) increased significantly reported a significant effect on baseline cerebral hemodynamics for the surgical mask by 4.1 mmHg (95% CI: 0.5, 7.6 mmHg) and and end-tidal carbon dioxide pressure (EtCO2) using functional 2.0 beats/min (95% CI: 1.0, 3.1 beats/min), respectively. Respira- MRI (fMRI) on middle-aged adults. No task-induced hemody- tory rate (RR) decreased significantly for the FFP2 mask by 3.2 namic changes were found in this study. The bulk of these con- breaths/min (95% CI: −5.4, −1.1 breaths/min). A significant dif- cerns arise due to potential hypercapnic effects of carbon dioxide ference in HR between mask types of 1.2 beats/min (95% CI: 0.0, rebreathing, which has not yet been evaluated in a thorough 2.4 beats/min) was detected. manner. Also, the brain function was evaluated only at the level of a surrogate of oxygen consumption. Noninvasive functional near- infrared spectroscopy (fNIRS) and functional diffuse correlation Author contributions: J.B.F., L.K.F., F.S., R.D.-M., M.M., and T.D. designed research; J.B.F. spectroscopy (fDCS) use near-infrared light to measure micro- and L.K.F. performed research; J.B.F. and L.K.F. analyzed data; J.B.F., F.S., and T.D. wrote vascular cerebral hemodynamics without the constraints of the the paper; J.B.F., L.K.F., F.S., R.D.-M., M.M., and T.D. interpreted data; F.S., M.M., and T.D. fMRI scanners. When combined together, they allow us to relate provided supervision; and R.D.-M. and T.D. provided administrative, technical, and cerebral blood/tissue oxygen saturation and blood flow to the ce- material support. rebral oxygen metabolism. Their main disadvantage is the poten- Competing interest statement: T.D. and J.B.F. are inventors on relevant patents. Institut de Ciències Fotòniques (ICFO) has equity ownership in the spin-off company HemoPho- tial signal contamination due to the extracerebral tissues and the tonics S.L. Potential financial conflicts of interest and objectivity of research have been limited penetration depth. Nevertheless, the advantage of studying monitored by ICFO’s Knowledge and Technology Transfer Department. mask effects on brain function in realistic settings merits their uses This open access article is distributed under Creative Commons Attribution License 4.0 for a thorough study to look at the physiology in a holistic manner. (CC BY). To this end, we have investigated the effect of mask wearing 1 J.B.F. and L.K.F. contributed equally to this work. (FFP2 [European Union standard, similar to N95 in North 2 To whom correspondence may be addressed. Email: turgut.durduran@icfo.eu. America and KN95 in China] versus surgical) on cerebral he- This article contains supporting information online at https://www.pnas.org/lookup/suppl/ modynamics, blood/tissue oxygenation, and oxygen metabolism doi:10.1073/pnas.2109111118/-/DCSupplemental. as well as the systemic physiology with a multimodal platform of Published October 4, 2021. PNAS 2021 Vol. 118 No. 41 e2109111118 https://doi.org/10.1073/pnas.2109111118 | 1 of 3 Brain tissue oxygenation, hemodynamics and metabolism Mask off Mask on 30 ↑ 6.5 (2.6, 10.5) ↑ 6.2 (2.4, 9.9) (↑ ~ 35) ΔrCBF 20 ΔrCBF [%]: ΔrCBF [%] 10 ΔStO2 [%]: ↑ 0.9 (0.2, 1.7) ↑ 0.9 (0.1, 1.6) (↑ ~ 5) 0 -10 ΔtHb [μM]: ↑ 0.9 (0.3, 1.5) 0.4 (-0.2, 0.9) (↑ ~ 3) 3 ΔStO2 ΔStO2 ΔrOEF [%]: -1.7 (-4.1, 0.8) -2.4 (-4.7, 0.0) (↓ ~ -7) 2 [%] 1 ΔrCMRO2 [%]: 4.5 (-1.3, 10.4) 3.6 (-1.7, 9.0) (↑ ~ 18) 0 -1 3 2 ΔtHb Systemic physiological parameters ΔtHb [μM] 1 ΔHR [1/min]: 0.8 (-0.3, 1.8) ↑ 2.0 (1.0, 3.1) 0 -1 ΔRR [1/min]: ↓ -3.2 (-5.4, -1.1) -0.5 (-2.6, 1.7) 5 ΔrOEF ΔTcCO2 [mmHg]: 0.4 (-0.2, 1.1) -0.1 (-0.7, 0.6) 0 [%] ΔSpO2 [%]: 0.1 (-0.2, 0.4) 0.0 (-0.4, 0.3) -5 ΔrOEF ΔMAP [mmHg]: 2.2 (-1.4, 5.7) ↑ 4.1 (0.5, 7.6) 40 ΔrCMRO2 20 ΔrCMRO2 [%] 0 FFP2 mask Surgical mask Typical change during a functional task 10 [1/min] ΔHR ΔHR 5 0 Optical probes with [1/min] 0 ΔRR DCS & TD-NIRS -5 ΔRR -10 1 [mmHg] ΔTcCO2 R L 0 -1 ΔTcCO2 -2 Downloaded from https://www.pnas.org by 158.109.91.150 on December 14, 2022 from IP address 158.109.91.150. 0.5 ΔSpO2 0.0 [%] -0.5 -1.0 ΔSpO2 10 [mmHg] ΔMAP ΔMAP 5 0 -5 For the analysis: -10 hemispheres (R, L) averaged -5 0 5 10 Time [min] Fig. 1. (Left) Changes in the different parameters are shown for FFP2 masks (red) and surgical masks (blue). “Δ” denotes a difference and “r” is a ratio. The arrow indicates a significant change (P < 0.05) whose direction is an increase or a decrease. Additionally, for cerebral hemodynamics, we have reported (green) changes during typical tasks such as basic cognitive, visual, or motor tasks (4, 8) for comparison. (Right) Time series of the population mean of all parameters are shown for both mask types (same color code). Time 0 is the time when the mask was placed and the shaded area indicates the time taken for placing the mask, which was excluded from the analysis. Data to the Right of the 3-min mark (magenta) were used for analysis to allow the physiology to stabilize after placing the mask. The data were normalized to 300 s prior to the mask placement. Discussion intersubject variability, which may be related to the fit of the mask, Our findings show that wearing a face mask leads to statistically mask types, and the individual’s physiology. significant changes in the cerebral hemodynamics and oxygena- Furthermore, we did not observe significant changes in TcCO2 tion (CBF and StO2) in healthy young subjects at rest, even for and SpO2. The increase in MAP and HR for the surgical mask this first relatively short period of mask usage. However, the may have been caused by the discomfort of probes, placement of changes observed are minimal and are comparable to those typi- masks, and the order of studies. Here, we did not account for cally observed during daily life (4). Within the limitations of the these stressors as potential confounding effects, since they are also part of daily life. This observation is further strengthened study, we cannot claim any concerns for mask use during daily life since TcCO2 did not change, i.e., the hypothesized hypercapnic activities for healthy, young individuals. In order to draw a effect was not observed. We stress that in the literature mainly stronger conclusion, the duration of mask wearing could have EtCO2 is utilized as a surrogate of blood carbon dioxide levels, been longer (harder to disentangle its effects from other physio- which, however, is influenced by the trapped carbon dioxide logical variables such as fatigue), the study population should be under the mask with standard equipment (5). TcCO2 provides more heterogeneous representing the society in general, and the insights as a better surrogate for the partial pressure of carbon sample sizes can be increased. Another limitation is the fact that dioxide. the order of the masks was fixed, therefore one should be critical Overall, our study provides a holistic view of understanding about the results regarding differences in the mask types and the potential effects of mask wearing in healthy, young adults by a additional differences may be revealed in the future. The notice- thorough characterization of both the systemic physiology, the able differences in variance of the time traces are related to the presumed driving biomarker of carbon dioxide rebreathing effect, 2 of 3 | PNAS Fischer et al. https://doi.org/10.1073/pnas.2109111118 Cerebral and systemic physiological effects of wearing face masks in young adults BRIEF REPORT and cerebral hemodynamics. The large intersubject variability and time-resolved near-infrared spectroscopy (TR-NIRS) (6). Changes in CBF, while wearing a mask suggests that individuals may have differing StO2, and tHb were determined. MAP, HR, SpO2, RR, EtCO2, and TcCO2 were responses and the platform/protocol that we introduce here could monitored. Signal processing was performed with Matlab (R2019a, Math- be utilized on elderly subjects or those with preexisting respiratory Works) and statistical analysis (R, v4.0.3) was applied to determine whether or cerebrovascular problems. These populations may behave dif- mask wearing was leading to a significant change in the signals. Raw DCS and TR-NIRS data were fitted using the analytical solution. Artifacts were manually ferently. Finally, the potential effect of mask wearing on individ- removed, the data were smoothed (30-s window), and the changes were av- uals performing critical tasks needs to be studied with future eraged over both hemispheres since no difference between them was de- investigations. Investigations of these effects are important for tected (P >> 0.5, paired Wilcoxon test). For further details see SI Appendix. policy making in order to maintain quality of life for individuals and for minimizing risks in persons carrying out critical tasks. Data Availability. Data for analysis and plots as txt files R code for analysis and plot have been deposited in Zenodo (10.5281/zenodo.4775432) (https://doi. Materials and Methods org/10.5281/zenodo.4775432) (7). The study protocol was approved by the ethical committee of Hospital Clinic Barcelona and all participants signed informed consent. Young healthy adults ACKNOWLEDGMENTS. This work was funded by la Fundació La Marató de (range for inclusion: 20 to 35 y of age) were recruited. Participants sat in a TV3 (201709.31, 201724.31); Fundació CELLEX Barcelona; Agencia Estatal de chair and read a scientific text during the experiments. The experimental Investigación (PHOTOMETABO, PID2019-106481RB-C31, PRE2018-085082); paradigm involved two 10-min periods: 1) without wearing a mask and 2) with a the “Severo Ochoa” (CEX2019-000910-S); “laCaixa” (LlumMedBcn); Institució mask. A commonly used three-layer surgical mask and a FFP2 mask (RM101 Centres de Recerca de Catalunya (CERCA), Agència de Gestió d’Ajuts Uni- FFP2 NR, Zhejiang Yinghua Technology Co. Ltd.) were tested. Cerebral blood versitaris i de Recerca (AGAUR)-Generalitat (2017SGR1380); RIS3CAT (CECH, flow, oxygenation, and oxygen metabolism were measured bilaterally over 001-P-001682); LASERLAB-EUROPE V and EU Horizon 2020 (BitMap 675332, the prefrontal cortex using transcranial diffuse correlation spectroscopy (DCS) VASCOVID 101016087, LUCA 688303, TinyBrains 101017113). 1. T. Czypionka, T. Greenhalgh, D. Basserl, M. B. Bryant, Masks and face coverings for the 5. F. 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