Repurposing Methylene Blue for the Management of COVID-19: Prospects, Paradox, and Perspective

COVID-19 onslaught has led to widespread morbidity and mortality globally. Another major concern, especially in developing countries like India, has been the development of fungal superinfection and colonization of other pathogens in hospitalized COVID-19 patients. Even though an armamentarium of repurposed, antiviral, anticytokine, and antifungal drugs is available to manage the disease progression, no single drug and/or therapy has provided positive clinical outcomes with efficacy and affordability. Therefore, it is imperative to explore innovative approaches for standalone treatment and/or adjunct therapeutic regimes based on our current understanding of disease prognosis. Low-income and emerging economies have less resources to protect themselves against the COVID-19-induced health and economic crisis. With the continuously evolving nature of coronavirus, a cost-effective strain independent mechanism that could be delivered easily even in a nonhealthcare setting is an urgent need of the hour. Methylene blue appears an apt candidate as it is an FDA-approved safe drug that is economically viable and easily available. Since MB has a long-standing history of being used in clinical setup for diverse medical applications and possesses intrinsic anti-inflammatory, anticytokine, and antifungal properties, this study analyzes prospects of its use in the management of COVID-19. Paradox and prospects of MB applications for the management of COVID-19, with or without fungal superinfections, are also discussed. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Diagnostic laparoscopy and dye test

Since the advent of laparoscopy, minimally invasive surgery has undergone significant advances and has changed the way operations are performed especially in the field of gynaecology, reproductive endocrinology and infertility, in both developed and developing countries. Hysterosalpingography remains the first-line tool in assessing tubal patency but laparoscopy and dye test is gaining momentum in some parts of the world. Laparoscopy and methylene blue dye test, while evaluating the fallopian tubes for patency, affords the opportunity to examine the peritoneal cavity and also inspects the adnexal structures for any pathology. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Methylene blue: a controversial diagnostic acid and medication?

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.

Synthesis Strategy of Tetrapyrrolic Photosensitizers for Their Practical Application in Photodynamic Therapy

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

Strategic use of thermo-chemical processes for plastic waste valorization

Plastic is one of the most widely used materials in industries including packaging, building, and construction due to its lightweight, low cost, durability, and versatility. However, the mass production of plastics has exacerbated plastic pollution. Globally, plastic waste is predominantly incinerated, landfilled, or released into the environment;only 5-6% is recycled in the United States. Although conventional management protocols such as incineration and landfilling are evidently effective for plastic waste disposal, they are associated with significant environmental and societal challenges. In addition, most recycled plastic is downcycled, and thus does not provide sufficient incentive to use recycled materials instead of virgin materials. This review discusses thermo-chemical upcycling processes such as (catalytic) pyrolysis and heterogeneous catalysis. Furthermore, we present the recent progress in the thermo-chemical upgrading of single-type plastic waste, heterogeneous plastic mixtures, and post-consumer plastic waste obtained from different locations and, finally, suggest future research directions.

Nasal photodisinfection in an industrial workplace for COVID-19 suppression

Antimicrobial photodynamic therapy (aPDT) [1] has been deployed in tens of thousands of patients in Canada for preoperative intranasal bacterial suppression to reduce the prevalence rate of surgical site infections [2]. This treatment has proven safe and effective, with infection rate reductions of 40-80% in tertiary care systems despite only requiring 4 minutes of therapy [2]. We previously demonstrated that aPDT eliminates the RNA signature of wild-type SARS-CoV-2 in vitro, with reduction of RT-qPCR threshold counts (DELTACt = 22) in a light-dose dependent manner (C = 320 muM, lambda = 664 nm, F = 36 J/cm2) [3]. Photodynamic targets were found to include the receptor binding domain, spike protein and nucleocapsid domain, consistent with a broad spectrum peroxidative effect on anionic moieties throughout the virion [3]. This work describes the benefits of using regular aPDT treatments in the industrial workplace for the purpose of employee COVID-19 prevention. From July 2020 to August 2021, aPDT was deployed at a large Canadian food processing plant. Meat processing facilities face distinctive challenges in control of infectious diseases, including SARS-CoV-2. Factors that increase processing workers' risk for exposure to SARS-CoV-2 include close contact for 8-12 hour shifts, shared transportation, and congregate housing [4,5]. The presence of a slaughtering plant in a community is associated with a 51 to 75% increase in COVID-19 cases per thousand over the baseline community rate, and a 37 to 50% increase in death rate over the baseline community rate [5]. Methylene blue-mediated aPDT (SteriwaveTM Nasal Photodisinfection System, Ondine Biomedical Inc., Vancouver, BC) was added to the standard infection control bundle at the plant, along with employee education. Treatments were administered free of charge to approximately 1,500 employees on a voluntary basis during paid work hours. Compliance levels of employees requesting aPDT were 85%. To determine intervention efficacy, the rate of qPCR-positive COVID-19 tests over the treatment time period was compared to the same rate in the surrounding province. Results demonstrated a reduction of COVID-19 rate of over 3 times (p<.0001, Fisher's Exact Test) in the treated population compared to the untreated population, with the largest adverse event being mild (self-limiting) rhinorrhea in < 1% of cases. The plant continued production and distribution of products without disruption. Important outcomes from this quality improvement initiative included (a) aPDT proved to be a rapid, lightweight intervention that could be deployed at high compliance levels in a commercial high-throughput food processing operation, (b) significant impact (>3X reduction) on the COVID-19 rates was observed and (c) COVID-19-related comorbidities including acute and long-term illness, disability, and death were proportionately avoided.Copyright © 2023

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

Development of a portable bioaerosol capture device for influenza virus detection

Many bacteria and viruses are spreading in the air in the living environment, and high concentrations of viruses entering the human body will cause harm. This research is committed to developing a virus collector, which is used to collect influenza and coronavirus in the air. In our system, the intake fan can beget negative pressure into the water circulation channel and bring the virus into it, and then the sensor chip will obtain the electrical signal. In this study, we successfully used methylene blue to simulate viruses in the air. The result of this experiment showed that the distance between the air virus collector and the atomizer was 30 cm in height, 60 cm & 90 cm in length. The capture efficiency was respectively 1.1% and 0.8%. Also, we use lateral flow immunochromatographic assay to detect the collected samples of Influenza H1N1 Hemagglutinin Protein, and the actual limit of detection is 16.97 ng/ml. In addition, the experiments also proved that the water circulation device in this study could accumulate the methylene blue samples onto the sensor. In the future, it can be used with the sensor chip as a virus detection platform which can collect and monitor viruses simultaneously. By using this device, people can be warned and take the necessary precautions to reduce the chance of the transmission of viruses.

Pathogen reduction with methylene blue does not have an impact on the clinical effectiveness of COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: There is a concern about a possible deleterious effect of pathogen reduction (PR) with methylene blue (MB) on the function of immunoglobulins of COVID-19 convalescent plasma (CCP). We have evaluated whether MB-treated CCP is associated with a poorer clinical response compared to other inactivation systems at the ConPlas-19 clinical trial. MATERIALS AND METHODS: This was an ad hoc sub-study of the ConPlas-19 clinical trial comparing the proportion of patients transfused with MB-treated CCP who had a worsening of respiration versus those treated with amotosalen (AM) or riboflavin (RB). RESULTS: One-hundred and seventy-five inpatients with SARS-CoV-2 pneumonia were transfused with a single CCP unit. The inactivation system of the CCP units transfused was MB in 90 patients (51.4%), RB in 60 (34.3%) and AM in 25 (14.3%). Five out of 90 patients (5.6%) transfused with MB-treated CCP had worsening respiration compared to 9 out of 85 patients (10.6%) treated with alternative PR methods (p = 0.220). Of note, MB showed a trend towards a lower rate of respiratory progressions at 28 days (risk ratio, 0.52; 95% confidence interval, 0.18-1.50). CONCLUSION: Our data suggest that MB-treated CCP does not provide a worse clinical outcome compared to the other PR methods for the treatment of COVID-19.

Clinical effectiveness and prospects of methylene blue A systematic review

Methylene blue (MB) is a well-known pharmaceutical ingredient that is thought to have a multi-targeted therapeutic effect as an anti-malarial and neuroprotective agent and has recently been identified as a treatment for coronavirus disease 2019 (COVID-19). In this review, we present an overview of relevant clinical trials, including ongoing trials, on the therapeutic uses of MB. A search for clinical trials on clinicaltrials.gov was performed using the terms "methylene blue" and "methylthionine chloride." This review focuses on clinical trials of MB-based therapies applied to brain diseases, cancer imaging and diagnosis, infectious diseases such as malaria or COVID-19, and cardiovascular diseases. Nanoparticle-based delivery techniques have also been briefly discussed in addition to common delivery methods.

Innovation in Teaching and Learning During Covid-19 Pandemic and Beyond: Absorption and Reflection Spectra with Low Cost Spectrometer

The work demonstrated that a low-cost spectrometer and ImageJ serve as an accurate, reliable, and robust model and tool for learners to grasp concepts in the Introductory Physics Lab Course context. The model design was self-paced while promoting active and peer learning for students. Image analysis within the experimental activity adds to the novelty of the lesson. Within the experimental accuracy, the measurement was shown to correctly identify the absorption spectra of Potassium Dichromate, Methylene Blue, and Potassium Permanganate and to describe the subtractive color-mixing model where Cyan absorbs Red accurately, Magenta absorbs Green, and Yellow absorbs Blue.

A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021-August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm2 for PDI and 4.9 J/cm2 for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12-24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of "long COVID" symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.

Photodynamic viral inactivation assisted by photosensitizers

The deadly viruses, which are spreading worldwide at an alarming rate, are a major challenge for the life sci-ences. More efficient and cost-effective methods with fewer side effects can provide a good alternative to traditional drug-based methods. Currently, physical phenomena such as light in the form of photodynamic action are increasingly being used to inactivate viruses. Photodynamic inactivation (PDI) uses a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS) to inactivate microorganisms. This article reviews the use of existing PSs, as one of the essential anti-viral agents, and introduces new materials and strategies combined with PDI. Physiochemical properties of PSs and their role in interaction with virus components are discussed. Furthermore, the effectiveness of optical sensitizers with radiation methods to inactivate viruses is highlighted.

Adsorption of Methylene Blue on the Surface of Polymer Membrane; Dependence on the Isotopic Composition of Liquid Matrix.

As was found in our previous works, when Nafion swells in water, polymer fibers unwind into the bulk of the surrounding liquid. This effect is controlled by the content of deuterium in water. Here, we present the results of studying the dynamics of methylene blue (MB) adsorption on the Nafion surface for MB solutions based on natural water (deuterium content is 157 ppm, the unwinding effect occurs) and based on deuterium-depleted water (DDW; deuterium content is 3 ppm, there is no unwinding). In addition, we studied the dynamics of water desorption during drying of the Nafion polymer membrane after soaking in MB solution based on natural water and DDW. It turned out that in the case of natural water, the rate of MB adsorption and water desorption is higher than in the case of DDW. It also turned out that the amount of MB adsorbed on the membrane in the case of natural water is greater than in the case of DDW. Finally, it was found that the desorption of water during drying is accompanied by a rearrangement of the absorption spectrum of Nafion. This rearrangement occurs earlier in the case of DDW. Thus, by infinitesimal changes in the deuterium content (from 3 to 157 ppm) in an aqueous solution, in which a polymer membrane swells, we can control the dynamics of adsorption and desorption processes. A qualitative model, which connects the observed effects with the slowing down of diffusion processes inside the layer of unwound fibers, is proposed.

Synthesis, Crystal Structure, Theoretical Calculations, Antibacterial Activity, Electrochemical Behavior, and Molecular Docking of Ni(II) and Cu(II) Complexes with Pyridoxal-Semicarbazone.

New Ni (II) and Cu (II) complexes with pyridoxal-semicarbazone were synthesized and their structures were solved by X-ray crystallography. This analysis showed the bis-ligand octahedral structure of [Ni(PLSC-H)2]·H2O and the dimer octahedral structure of [Cu(PLSC)(SO4)(H2O)]2·2H2O. Hirshfeld surface analysis was employed to determine the most important intermolecular interactions in the crystallographic structures. The structures of both complexes were further examined using density functional theory and natural bond orbital analysis. The photocatalytic decomposition of methylene blue in the presence of both compounds was investigated. Both compounds were active toward E. coli and S. aureus, with a minimum inhibition concentration similar to that of chloramphenicol. The obtained complexes led to the formation of free radical species, as was demonstrated in an experiment with dichlorofluorescein-diacetate. It is postulated that this is the mechanistic pathway of the antibacterial and photocatalytic activities. Cyclic voltammograms of the compounds showed the peaks of the reduction of metal ions. A molecular docking study showed that the Ni(II) complex exhibited promising activity towards Janus kinase (JAK), as a potential therapy for inflammatory diseases, cancers, and immunologic disorders.

REFRACTORY HYPOXEMIA: A CASE OF DAPSONE-INDUCED METHEMOGLOBINEMIA IN A PATIENT WITH COVID-19

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Methemoglobinemia is an increase in methemoglobin (mHb) level characterized by functional anemia and tissue hypoxia. It can be caused by congenital enzymes deficiencies, but it is usually acquired. Dapsone, an oxidizing agent, is a medication commonly associated with acquired methemoglobinemia (1). We describe the diagnosis and management of a COVID-19 patient with acquired methemoglobinemia due to Dapsone. CASE PRESENTATION: 84-year-old female with history of MPO-ANCA vasculitis with renal involvement, CKD4 and anemia of chronic disease presented with shortness of breath, lethargy and weakness. Initially, the patient was saturating (SpO2) 80% on room air and was placed on 4L nasal cannula (NC) with improvement to 92%. CT of the chest showed b/l GGOs consistent with atypical pneumonia and patient tested positive for COVID-19. About 4 months prior, she had received 2 doses of Rituximab and on high steroid therapy that was tapered to 5mg of prednisone daily. She has been on Trimethoprim/Sulfamethoxazole for PJP prophylaxis, but due to hyperkalemia the medication was stopped. After confirming no G6PD deficiency, she was started on Dapsone 100mg daily. During hospitalization, she was given dexamethasone 6 mg daily and Dapsone was continued. On hospital stay day 6, a rapid response was called after oxygen dropped to 78% while walking on 6L NC. She was placed on high flow NC 100% and SpO2 went up to 90%. An arterial blood gas (ABG) was then obtained showing pO2 of 334, oxyhemoglobin (oxyHb) of 83 and mHb of 17.4. The SpO2-PaO2 gap and elevated mHb lead to the diagnosis of Dapsone-induced methemoglobinemia. Dapsone was discontinued. Patient received a one-time dose of 1mg/kg IV of methylene blue. One hour later her dyspnea had improved and was on 3L NC. Repeat ABG showed improvement of oxyHb (98) and decreased mHb (2.2). DISCUSSION: Physiologically, mHb is less than 1% of total Hb (1) and occurs when the iron in the porphyrin group of heme is oxidized from ferrous to the ferric form (2). Ferric heme binds oxygen irreversibly causing a left shift of the oxygen-hemoglobin dissociation curve. Clinical presentation tends to correlate with mHb levels, and it varies from being asymptomatic to fatigue, dyspnea, confusion, seizure, cyanosis resistant to oxygen therapy (mHb > 15%) and death. Methylene blue is safe and can be consider when mHb level is greater than 10 to 20% (2). Methylene blue was administer to our patient given the presence of COVID (leaving patient more susceptible to medication-induced methemoglobinemia (3)) and chronic anemia which made her less likely to tolerate state of reduced oxygen delivery. CONCLUSIONS: The diagnosis of methemoglobinemia is a rare cause of hypoxemia that is often overlooked. In patients with risk factors (COVID, medication exposure) a high index of suspicion is needed when interpreting an ABG (SpO2-PaO2 gap) for correct diagnosis and appropriate treatment. Reference #1: Toker, Ibrahim, et al. "Methemoglobinemia Caused by Dapsone Overdose: Which Treatment Is Best?” Turkish Journal of Emergency Medicine, vol. 15, no. 4, Dec. 2015, pp. 182–184, 10.1016/j.tjem.2014.09.002. Accessed 31 Aug. 2020. Reference #2: Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for management. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):1043-7. doi: 10.1053/j.jvca.2013.02.005. Epub 2013 Aug 13. PMID: 23953868. Reference #3: Naymagon, Leonard, et al. "The Emergence of Methemoglobinemia amidst the COVID -19 Pandemic.” American Journal of Hematology, vol. 95, no. 8, 3 June 2020, 10.1002/ajh.25868. Accessed 3 Mar. 2021. DISCLOSURES: No relevant relationships by Mileydis Alonso No relevant relationships by Samantha Gillenwater No relevant relationships by Christine Girard No relevant relationships by Sikandar Khan No relevant relationships by Jose Rivera No relevant relationships by Frederick Ross

DAPSONE-INDUCED METHEMOGLOBINEMIA IN COVID-19: A MIMIC OF “HAPPY HYPOXIA”

SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: COVID-19 has been notorious to cause "happy hypoxia” or presentation with profound hypoxia yet without proportional signs of respiratory distress. Methemoglobinemia is a rare and potentially life threatening condition characterized by an inability of hemoglobin to bind oxygen leading to diffuse tissue hypoxia. Diagnosis of methemoglobinemia in a patient with COVID-19 may be masked if the index of suspicion is low. We present such case of dapsone-induced methemoglobinemia in the setting of COVID-19. CASE PRESENTATION: A 64-year-old male presented to the hospital with fatigue. His past medical history included Type 1 Diabetes Mellitus (DM), hypertension and dermatitis herpetiformis. He also reported a 6 day history of testing positive for COVID-19 as an outpatient. His initial vital signs were stable and his peripheral oximeter showed a 96% saturation on 2L O2. Physical exam was unremarkable without any signs of respiratory distress. His labs were notable for blood glucose of 500, high anion gap metabolic acidosis concerning for diabetic ketoacidosis (DKA). A chest X-ray (CXR) revealed bilateral infiltrates. He was initiated on insulin drip and per hospital protocol initiated on Remdesevir and Decadron for COVID-19 treatment. Patient's DKA subsequently resolved. However on Day 4, patient's oxygen saturation decreased suddenly to the 80s without any signs of respiratory distress. Infectious workup including CBC, sputum culture, antigen for streptococcus, legionella returned negative. His CXR remained unchanged. Arterial blood gas (ABG) demonstrated pH of 7.45, pCo2 46mm Hg, pO2 157 mm Hg. Methemoglobin level was found to be 14.1%. He was given methylene blue 1 mg/kg and dapsone was discontinued. His methemoglobin level improved to 3.4% the next day. He was subsequently discharged home without need for supplemental oxygen. DISCUSSION: Methemoglobinemia can be acquired through drugs that oxidize the ferrous hemoglobin to ferric form. Dapsone is one such agent commonly used for dermatological conditions and opportunistic infection prophylaxis. The oxidative stress caused due to COVID-19 coupled with Dapsone use may have precipitated methemoglobinemia in our patient. Since the presentation can easily mimic "happy hypoxia", index of suspicion for methemoglobinemia can be low and thus can have profound consequences if undetected and not treated. CONCLUSIONS: In the setting of COVID-19 pneumonia with refractory hypoxemia, clinicians should have a high index of suspicion for methemoglobinemia especially in patients on highly oxidative medications. Reference #1: Burke P, et al. Dapsone-induced methemoglobinemia: case of the blue lady. Can Fam Physician. 2013 Sep;59(9):958-61. Reference #2: Naymagon L., Berwick S., Kessler A., et al. The emergence of methemoglobinemia amidst the COVID-19 pandemic. Am. J. Hematol. 2020;95: E196-E197 https://doi.org/10.1002/ajh.25868 Reference #3: Faisal H, Bloom A, Gaber AO. Unexplained Methemoglobinemia in Coronavirus Disease 2019: A Case Report. A&A Pract. 2020;14(9):e01287. doi:10.1213/XAA.0000000000001287 DISCLOSURES: No relevant relationships by Syed Azharuddin Speaker/Speaker's Bureau relationship with gsk Please note: 2020-present by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: 2020 Added 04/14/2022 by Tariq Cheema, value=Honoraria Removed 04/14/2022 by Tariq Cheema Speaker/Speaker's Bureau relationship with BI Please note: 2020-PRESENT Added 04/14/2022 by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with astra zeneca Please note: 2020-Present Added 04/14/2022 by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with regeneron Please note: 2021-Present Added 04/14/2022 by Tariq Cheema, value=Honoraria No relevant relationships by Deeksha Ramanujam No relevant relationships by Alisha Sharma

Rutile-TiO2/PtO2 Glass Coatings Disinfects Aquatic Legionella pneumophila via Morphology Change and Endotoxin Degradation under LED Irradiation

Legionella pneumophila (L. pneumophila) is the causative agent of Legionnaires’ disease and Pontiac fever, collectively known as legionellosis. L. pneumophila infection occurs through inhalation of contaminated aerosols from water systems in workplaces and institutions. The development of disinfectants that can eliminate L. pneumophila in such water systems without evacuating people is needed to prevent the spread of L. pneumophila. Photocatalysts are attractive disinfectants that do not harm human health. In particular, the TiO2 photocatalyst kills L. pneumophila under various conditions, but its mode of action is unknown. Here, we confirmed the high performance of TiO2 photocatalyst containing PtO2 via the degradation of methylene blue (half-value period: 19.2 min) and bactericidal activity against Escherichia coli (half-value period: 15.1 min) in water. Using transmission electron microscopy, we demonstrate that the disinfection of L. pneumophila (half-value period: 6.7 min) by TiO2 photocatalyst in water is accompanied by remarkable cellular membrane and internal damage to L. pneumophila. Assays with limulus amebocyte lysate and silver staining showed the release of endotoxin from L. pneumophila due to membrane damage and photocatalytic degradation of this endotoxin. This is the first study to demonstrate the disinfection mechanisms of TiO2 photocatalyst, namely, via morphological changes and membrane damage of L. pneumophila. Our results suggest that TiO2 photocatalyst might be effective in controlling the spread of L. pneumophila.

Antimicrobial Activity of a Titanium Dioxide Additivated Thermoset

The transmission of pathogens via surfaces poses a major health problem, particularly in hospital environments. Antimicrobial surfaces can interrupt the path of spread, while photocatalytically active titanium dioxide (TiO2) nanoparticles have emerged as an additive for creating antimicrobial materials. Irradiation of such particles with ultraviolet (UV) light leads to the formation of reactive oxygen species that can inactivate bacteria. The aim of this research was to incorporate TiO2 nanoparticles into a cellulose-reinforced melamine-formaldehyde resin (MF) to obtain a photocatalytic antimicrobial thermoset, to be used, for example, for device enclosures or tableware. To this end, composites of MF with 5, 10, 15, and 20 wt% TiO2 were produced by ultrasonication and hot pressing. The incorporation of TiO2 resulted in a small decrease in tensile strength and little to no decrease in Shore D hardness, but a statistically significant decrease in the water contact angle. After 48 h of UV irradiation, a statistically significant decrease in tensile strength for samples with 0 and 10 wt% TiO2 was measured but with no statistically significant differences in Shore D hardness, although a statistically significant increase in surface hydrophilicity was measured. Accelerated methylene blue (MB) degradation was measured during a further 2.5 h of UV irradiation and MB concentrations of 12% or less could be achieved. Samples containing 0, 10, and 20 wt% TiO2 were investigated for long-term UV stability and antimicrobial activity. Fourier-transform infrared spectroscopy revealed no changes in the chemical structure of the polymer, due to the incorporation of TiO2, but changes were detected after 500 h of irradiation, indicating material degradation. Specimens pre-irradiated with UV for 48 h showed a total reduction in Escherichia coli when exposed to UV irradiation.