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      COVID-19 and increasing demand for medical oxygen: can impurity be a problem ?

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          Abstract

          Introduction The COVID-19 pandemic in 2021 has accelerated the demand for oxygen supplies globally. Many countries have not seen such high demand before the pandemic to meet their daily oxygen requirement (Usher 2021). Worldwide, governments are scaling up their existing facilities to fill the oxygen demand. In the healthcare system, oxygen is an essential medicine required at all levels. It is estimated that 20–40% of deaths due to pneumonia could be prevented using oxygen therapy (WHO 2021). Medical air in hospital settings is widely used for mechanical ventilation, infant resuscitation, aerosol drug delivery, and neonatal environment control (Edwards et al. 2018). Oxygen cylinders, oxygen concentrators, liquid oxygen, and membrane separator oxygen enrichers are commonly used for oxygen therapy (Rees and Dudley 1998). In the current COVID-19 pandemic, long-term oxygen therapy is required at both hospitals and in-home settings that the respiratory physician should supervise for optimal treatment (Rees and Dudley 1998). Unprecedented production of oxygen and refilling of cylinders can give rise to the risk of impurities, which could lead to an increase in hidden mortality. However, it would be difficult to assess the increase in mortality due to the impurity of the oxygen gas. Hence, the purity of the oxygen needs to be regulated by the respective authorities (Edwards et al. 2018). Higher oxygen production can give rise to a possibility of contamination. In a recent study, the CO2 impurity was reported in oxygen cylinders above the recommended threshold level (Edwards et al. 2018). In previous studies, various health effects were reported due to the common air pollutants (WHO 2005). It was also observed that unintentional inhalation of NO in industrial regions might change the PaO2 (Benzing et al. 1999). Edwards et al. (2018) also mentioned onsite production of medical air poses a risk of raising the CO2 and NOx (nitric oxides) concentration above the United States Pharmacopeia (USP) threshold (Edwards et al. 2018). This rise of these trace gases may be due to the dryer that is used to capture the CO2 contaminant and humidity. Impurity sources can be arising due to the production and delivery systems, as well as from the environmental pollution levels near the regions. According to the FDA guidelines, medical gases should be checked for any adulteration during production, packaging, delivery, and manufacturing facilities (FDA 2015). Here, we would like to highlight few points for policymakers/local authorities (Table 1) and for the general public (Table 2) to create awareness and recommendations to improve the quality of oxygen. Table 1 Interventions required by policymakers or local authorities Monitor gas testing facilities, laboratories, and calibration facilities at the site To ensure compliance and procedures of finished gas for its quality Purity and grade (ultra-pure, 99.999% minimum) should be maintained A random check of tankers and especially cylinders for chemical analysis of oxygen gases Impurity parameters certificate should be provided for the levels (i.e., carbon monoxide/carbon dioxide, moisture, arsenic, oil, halogen, oxidizing substances, acidity or alkalinity, argon, hydrocarbons) Test results can be cross-checked by the local authority for any foreign materials, moisture, and contaminants To monitor any misuse of other cylinders (i.e., helium, hydrogen, acetylene, argon) for refilling oxygen without proper cleaning and conditioning Monitoring for the sanitization of oxygen supply (pipeline and tubes) for unwanted fungal growth Special attention should be given to test “black fungus” (mucormycosis) infection among recovered patients Checking/advisory for black fungus on patients on oxygen support should be made an essential part of the COVID-19 control protocol at every level Special attention/care should be given to comorbid and patients using the steroid to check the fungal infection for the hidden cause of death Table 2 Recommendation/awareness needed for the general public Oxygen gas cylinder should be kept at normal room temperature Always use distilled water to make oxygen hydrated before use Never use poor-quality water such as tap water, boiled water, or purified RO water Masks, nasal cannulae should be cleaned and checked for any leakage by the attendee If using an oxygen concentrator, attendee should adhere to manufacturer guidelines for proper cleaning as and when required The oxygen concentrator should be placed in a well-ventilated and clean area Oxygen filters should be properly cleaned from time to time Avoid smoking (wood, cigarette, sticks) in any form, active or passive, near to oxygen concentrator Attendee can monitor patient nostril for any black pigmentation, as soon as it is noticed even as the smallest spot contact doctor immediately for further treatment Avoid irrational use of steroids without recommendations Another reason for the increase in the COVID-19 mortality can also be due to the black fungus, which are present in the environment (Richardson 2009). This could lead to mucormycosis, which could be a fatal disease for people who have weakened immune systems (Spellberg et al. 2005). In the nasal tract, black fungus develop due to the poor quality of water used to hydrate the oxygen in a hospital setting (piped and cylinders). This fungus grows in the nostril, travels towards the eyes (Klotz et al. 2000), and then towards the brain, which can paralyze the nerves (Escobar and Del Brutto 1990), cause permanent damage to the eye, or even could lead to a heart attack (Naik et al. 2021; Jackman and Simonsen 1992). An evidence-based advisory for screening, diagnosis, and management of mucormycosis developed by Cornely et al. (2019) should be followed and need to be updated considering the recent evidence of mucormycosis in the COVID-19 pandemic (Cornely et al. 2019). In a hospital setting, constantly monitor distilled water for oxygen hydration before using it in oxygen therapy devices (Cahill and Heath 1990). Use of tap water even after boiling is not recommended in the humidifier as after some time; impurities (micro-metals and minerals/salts) start to buildup, leading to severe health issues even after using life-saving precious oxygen therapy. Globally, we are facing an emergency that needs support from authorities and the community to minimize the suffering and improve the well-being of all. In lower- and middle-income countries, oxygen purity can be a significant issue that requires local interventions at the earliest. Countries where there is prevalence of malaria, sepsis, pneumonia, and other ailments should also prioritize where oxygen therapy requires at large (Usher 2021).

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          Most cited references12

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          Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

          Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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            Novel perspectives on mucormycosis: pathophysiology, presentation, and management.

            Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement.
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              The ecology of the Zygomycetes and its impact on environmental exposure.

              Zygomycetes are unique among filamentous fungi in their great ability to infect a broader, more heterogeneous population of human hosts than other opportunistic moulds. Various members of the Zygomycetes have been implicated in zygomycosis, although those belonging to the family Mucoraceae are isolated more frequently than those of any other family. The environmental microbiology literature provides limited insights into how common zygomycetes are in the environment, and provides a few clues about which ecological niches these fungi are found in. Mucorales are thermotolerant moulds that are supposedly ubiquitous in nature and widely found on organic substrates, including bread, decaying fruits, vegetable matter, crop debris, soil between growing seasons, compost piles, and animal excreta. The scientific and medical literature does not support this generalization. Sporangiospores released by mucorales range from 3 to 11 microm in diameter, are easily aerosolized, and are readily dispersed throughout the environment. This is the major mode of transmission. However, there are very few data concerning the levels of zygomycete sporangiospores in outdoor and indoor air, especially in geographical areas where zygomycosis is particularly prevalent. Airborne fungal spores are almost ubiquitous and can be found on all human surfaces in contact with air, especially on the upper and lower airway mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly, members of the Mucorales are very rarely found in nasal mucus, suggesting that spores in the mucus of airway mucosa are cleared by mucociliary transport or that there is a low level of airborne contamination. Zygomycetes are found occasionally in water-damaged buildings, as demonstrated by air-sampling, and analysis of settled dust by quantitative PCR. Moreover, inhalation of sporangiospores in dust has been linked to outbreaks of rhinocerebral or pulmonary zygomycosis due to excavation, construction, or contaminated air-conditioning filters. Whereas most zygomycete infections are community-acquired, nosocomial acquisition due to percutaneous routes of exposure is very important. Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages and adhesive dressings, needles, and tongue depressors used to construct splints for intravenous and arterial cannulation sites in preterm infants. Insect bites or stings have been implicated in disease transmission in cases of cutaneous and subcutaneous zygomycosis, e.g. diseases caused by the Entomophthorales. Traumatic implantation of spores in dirt or in contaminated water, e.g. as occurred during the Asian tsunami, has led to infection in multiple patients.
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                Author and article information

                Contributors
                meenusingh4@gmail.com
                Journal
                Environ Sci Pollut Res Int
                Environ Sci Pollut Res Int
                Environmental Science and Pollution Research International
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0944-1344
                1614-7499
                17 September 2021
                : 1-3
                Affiliations
                [1 ]GRID grid.415131.3, ISNI 0000 0004 1767 2903, Department of Pediatrics, , Post Graduate Institute of Medical Education and Research (PGIMER), ; Chandigarh, 160012 India
                [2 ]GRID grid.415131.3, ISNI 0000 0004 1767 2903, Department of Community Medicine and School of Public Health, , Post Graduate Institute of Medical Education and Research (PGIMER), ; Chandigarh, 160012 India
                Author notes

                Responsible Editor: Lotfi Aleya

                Article
                16385
                10.1007/s11356-021-16385-x
                8448390
                34535859
                77d4b0e6-092c-404d-89b1-b67faa0aea30
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 August 2021
                : 2 September 2021
                Categories
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                General environmental science
                General environmental science

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