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

Background: As face masks became mandatory in most countries during the COVID-19 pandemic, adverse effects require substantiated investigation. Methods: A systematic review of 2,168 studies on adverse medical mask effects yielded 54 publications for synthesis and 37 studies for meta-analysis (on n = 8,641, m = 2,482, f = 6,159, 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 surgical and N95 masks, with a greater impact of the second. These effects included decreased SpO2 (overall Standard Mean Difference, SMD = -0.24, 95% CI = -0.38 to -0.11, p < 0.001) and minute ventilation (SMD = -0.72, 95% CI = -0.99 to -0.46, p < 0.001), simultaneous increased in blood-CO2 (SMD = +0.64, 95% CI = 0.31-0.96, p < 0.001), 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 < 0.001). 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 n = 373 with a robust relationship to mask wearing (p < 0.006 to p < 0.001). Pooled symptom prevalence (n = 8,128) was significant for: headache (62%, p < 0.001), acne (38%, p < 0.001), skin irritation (36%, p < 0.001), dyspnoea (33%, p < 0.001), heat (26%, p < 0.001), itching (26%, p < 0.001), 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 are shorter than daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES) and down-stream physio-metabolic disfunctions. MIES can have long-term clinical consequences, especially for vulnerable groups. So far, several mask related symptoms may have been misinterpreted as long COVID-19 symptoms. In any case, the possible MIES contrasts with the WHO definition of health. Conclusion: Face mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions. In the absence of strong empirical evidence of effectiveness, mask wearing should not be mandated let alone enforced by law. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256694, identifier: PROSPERO 2021 CRD42021256694.

Advanced setup for safe breath sampling and patient monitoring under highly infectious conditions in the clinical environment.

Being the proximal matrix, breath offers immediate metabolic outlook of respiratory infections. However, high viral load in exhalations imposes higher transmission risk that needs improved methods for safe and repeatable analysis. Here, we have advanced the state-of-the-art methods for real-time and offline mass-spectrometry based analysis of exhaled volatile organic compounds (VOCs) under SARS-CoV-2 and/or similar respiratory conditions. To reduce infection risk, the general experimental setups for direct and offline breath sampling are modified. Certain mainstream and side-stream viral filters are examined for direct and lab-based applications. Confounders/contributions from filters and optimum operational conditions are assessed. We observed immediate effects of infection safety mandates on breath biomarker profiles. Main-stream filters induced physiological and analytical effects. Side-stream filters caused only systematic analytical effects. Observed substance specific effects partly depended on compound's origin and properties, sampling flow and respiratory rate. For offline samples, storage time, -conditions and -temperature were crucial. Our methods provided repeatable conditions for point-of-care and lab-based breath analysis with low risk of disease transmission. Besides breath VOCs profiling in spontaneously breathing subjects at the screening scenario of COVID-19/similar test centres, our methods and protocols are applicable for moderately/severely ill (even mechanically-ventilated) and highly contagious patients at the intensive care.

Profiling of exhaled volatile organics in the screening scenario of a COVID-19 test center.

Breath volatile organics (VOCs) may provide immediate information on infection mechanisms and host response. We conducted real-time mass spectrometry-based breath profiling in 708 non-preselected consecutive subjects in the screening scenario of a COVID-19 test center. Recruited subjects were grouped based on PCR-confirmed infection status and presence or absence of flu-like symptoms. Exhaled VOC profiles of SARS-CoV-2-positive cases (n = 36) differed from healthy (n = 256) and those with other respiratory infections (n = 416). Concentrations of most VOCs were suppressed in COVID-19. VOC concentrations also differed between symptomatic and asymptomatic cases. Breath markers mirror effects of infections onto host's cellular metabolism and microbiome. Downregulation of specific VOCs was attributed to suppressive effects of SARS-CoV-2 onto gut or pulmonary microbial metabolism. Breath analysis holds potential for monitoring SARS-CoV-2 infections rather than for primary diagnosis. Breath profiling offers unconventional insight into host-virus cross-talk and infection microbiology and enables non-invasive assessment of disease manifestation.

Effects of COVID-19 protective face masks and wearing durations on respiratory haemodynamic physiology and exhaled breath constituents.

BACKGROUND: While assumed to protect against coronavirus transmission, face masks may have effects on respiratory-haemodynamic parameters. Within this pilot study, we investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 adults at rest. METHODS: We continuously monitored exhaled breath profiles within mask space in older (age 60-80 years) and young to middle-aged (age 20-59 years) adults over the period of 15 and 30 min by high-resolution real-time mass-spectrometry. Peripheral oxygen saturation (S pO2 ) and respiratory and haemodynamic parameters were measured (noninvasively) simultaneously. RESULTS: Profound, consistent and significant (p≤0.001) changes in S pO2 (≥60_FFP2-15 min: 5.8±1.3%↓, ≥60_surgical-15 min: 3.6±0.9%↓, <60_FFP2-30 min: 1.9±1.0%↓, <60_surgical-30 min: 0.9±0.6%↓) and end-tidal carbon dioxide tension (P ETCO2 ) (≥60_FFP2-15 min: 19.1±8.0%↑, ≥60_surgical-15 min: 11.6±7.6%↑, <60_FFP2- 30 min: 12.1±4.5%↑, <60_surgical- 30 min: 9.3±4.1%↑) indicate ascending deoxygenation and hypercarbia. Secondary changes (p≤0.005) to haemodynamic parameters (e.g. mean arterial pressure (MAP) ≥60_FFP2-15 min: 9.8±10.4%↑) were found. Exhalation of bloodborne volatile metabolites, e.g. aldehydes, hemiterpene, organosulfur, short-chain fatty acids, alcohols, ketone, aromatics, nitrile and monoterpene mirrored behaviour of cardiac output, MAP, S pO2 , respiratory rate and P ETCO2 . Exhaled humidity (e.g. ≥60_FFP2-15 min: 7.1±5.8%↑) and exhaled oxygen (e.g. ≥60_FFP2-15 min: 6.1±10.0%↓) changed significantly (p≤0.005) over time. CONCLUSIONS: Breathomics allows unique physiometabolic insights into immediate and transient effects of face mask wearing. Physiological parameters and breath profiles of endogenous and/or exogenous volatile metabolites indicated putative cross-talk between transient hypoxaemia, oxidative stress, hypercarbia, vasoconstriction, altered systemic microbial activity, energy homeostasis, compartmental storage and washout. FFP2 masks had a more pronounced effect than surgical masks. Older adults were more vulnerable to FFP2 mask-induced hypercarbia, arterial oxygen decline, blood pressure fluctuations and concomitant physiological and metabolic effects.