with the virus name (severe acute respiratory syndrome-coronavirus-2) [4]. Although infection
fatality rate (number of death cases divided by number of reported cases) initially seems quite
high 0.029 (2.9%) [4], this overestimation related to limited number of COVID-19 tests
performed which biases towards higher rates. Given the fact that asymptomatic or minimally
symptomatic cases is several times higher than the number of reported cases, the case fatality
rate is considerably less than 1% [5]. This was confirmed by the head of National Institute of
Allergy and Infectious Diseases from US stating, “the overall clinical consequences of COVID19 are similar to those of severe seasonal influenza” [5], having a case fatality rate of
approximately 0.1% [5], [6], [7], [8]. In addition, data from hospitalized patients with COVID-19
and general public indicate that the majority of deaths were among older and chronically ill
individuals, supporting the possibility that the virus may exacerbates existing conditions but
rarely causes death by itself [9], [10]. SARS-CoV-2 primarily affects respiratory system and can
cause complications such as acute respiratory distress syndrome (ARDS), respiratory failure
and death [3], [9]. It is not clear however, what the scientific and clinical basis for wearing
facemasks as protective strategy, given the fact that facemasks restrict breathing, causing
hypoxemia and hypercapnia and increase the risk for respiratory complications, selfcontamination and exacerbation of existing chronic conditions [2], [11], [12], [13], [14].
Of note, hyperoxia or oxygen supplementation (breathing air with high partial O2 pressures that
above the sea levels) has been well established as therapeutic and curative practice for variety
acute and chronic conditions including respiratory complications [11], [15]. It fact, the current
standard of care practice for treating hospitalized patients with COVID-19 is breathing 100%
oxygen [16], [17], [18]. Although several countries mandated wearing facemask in health care
settings and public areas, scientific evidences are lacking supporting their efficacy for reducing
morbidity or mortality associated with infectious or viral diseases [2], [14], [19]. Therefore, it has
been hypothesized: 1) the practice of wearing facemasks has compromised safety and efficacy
profile, 2) Both medical and non-medical facemasks are ineffective to reduce human-to-human
transmission and infectivity of SARS-CoV-2 and COVID-19, 3) Wearing facemasks has adverse
physiological and psychological effects, 4) Long-term consequences of wearing facemasks on
health are detrimental.

Evolution of hypothesis
Breathing Physiology
Breathing is one of the most important physiological functions to sustain life and health. Human
body requires a continuous and adequate oxygen (O2) supply to all organs and cells for normal
function and survival. Breathing is also an essential process for removing metabolic byproducts
[carbon dioxide (CO2)] occurring during cell respiration [12], [13]. It is well established that
acute significant deficit in O2 (hypoxemia) and increased levels of CO2 (hypercapnia) even for
few minutes can be severely harmful and lethal, while chronic hypoxemia and hypercapnia
cause health deterioration, exacerbation of existing conditions, morbidity and ultimately mortality
[11], [20], [21], [22]. Emergency medicine demonstrates that 5–6 min of severe hypoxemia
during cardiac arrest will cause brain death with extremely poor survival rates [20], [21], [22],
[23]. On the other hand, chronic mild or moderate hypoxemia and hypercapnia such as from
wearing facemasks resulting in shifting to higher contribution of anaerobic energy metabolism,
decrease in pH levels and increase in cells and blood acidity, toxicity, oxidative stress, chronic
inflammation, immunosuppression and health deterioration [24], [11], [12], [13].

Efficacy of facemasks
The physical properties of medical and non-medical facemasks suggest that facemasks are
ineffective to block viral particles due to their difference in scales [16], [17], [25]. According to
the current knowledge, the virus SARS-CoV-2 has a diameter of 60 nm to 140 nm [nanometers
(billionth of a meter)] [16], [17], while medical and non-medical facemasks’ thread diameter
ranges from 55 µm to 440 µm [micrometers (one millionth of a meter), which is more than 1000
times larger [25]. Due to the difference in sizes between SARS-CoV-2 diameter and facemasks
thread diameter (the virus is 1000 times smaller), SARS-CoV-2 can easily pass through any

2