Treatment of infection and inflammation associated with COVID-19, multi-drug resistant pneumonia and fungal sinusitis by nebulizing a nanosilver solution.

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.

Pharmacokinetic Evidence of Steady and Sustained Drug Release from Long-Acting Implantable Corticosteroid Matrices for Chronic Rhinosinusitis.

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.

Deadly Fungi: Invasive Fungal Rhinosinusitis in the Head and Neck.

Invasive fungal rhinosinusitis (IFRS) is a serious infection that is associated with high morbidity and mortality rates. The incidence of IFRS has been increasing, mainly because of the increased use of antibiotics and immunosuppressive drugs. Rhino-orbital cerebral mucormycosis has recently reemerged among patients affected by COVID-19 and has become a global concern. The detection of extrasinus involvement in its early stage contributes to improved outcomes; therefore, imaging studies are essential in establishing the degree of involvement and managing the treatment properly, especially in immunocompromised patients. The common sites of extrasinus fungal invasion are the intraorbital, cavernous sinus, and intracranial regions. Fungi spread directly to these regions along the blood vessels or nerves, causing devastating complications such as optic nerve ischemia or compression, optic neuritis or perineuritis, orbital cellulitis, cavernous sinus thrombosis, mycotic aneurysm, vasculitis, internal carotid arterial occlusion, cerebral infarction, cerebritis, and brain abscess. IFRS has a broad imaging spectrum, and familiarity with intra- and extrasinonasal imaging features, such as loss of contrast enhancement of the affected region, which indicates tissue ischemia due to angioinvasion of fungi, and the surrounding anatomy is essential for prompt diagnosis and management. The authors summarize the epidemiology, etiology, risk factors, and complications of IFRS and review the anatomy and key diagnostic imaging features of IFRS beyond the sinonasal regions. ©RSNA, 2022.

Management of complicated acute sinusitis in the setting of concurrent COVID-19.

PURPOSE: Intraorbital and intracranial complications of acute bacterial rhinosinusitis require timely medical and surgical treatment to prevent the development of long-term neurologic sequelae. The era of Coronavirus Disease-2019 (COVID-19) has complicated the management of complicated acute rhinosinusitis, especially when patients have concurrent acute sinusitis and COVID-19 infection. This case series aims to highlight the clinical course of pediatric patients at a single tertiary pediatric hospital with concurrent complicated bacterial rhinosinusitis and COVID-19. MATERIALS AND METHODS: A search of pediatric patients treated for COVID-19 and complications from acute sinusitis was performed using billing records for the year 2020-2021 at a single pediatric tertiary hospital. Data regarding presentation, management, microbiology, and hospital course was collected for review. RESULTS: A total of 6 patients with complicated bacterial sinusitis in the setting of COVID-19 infection were included. All patients were initially managed with medical therapy, consisting of systemic antibiotics, but 3 of these patients ultimately required surgical intervention. Cultures from the cohort grew Staphylococcus aureus, streptococcus intermedius, streptococcus constellatus or Prevotella species. All patients experienced clinical improvements and were eventually discharged home with oral antibiotics. CONCLUSION: COVID-19 continues to be an unusual disease especially for the pediatric population. Concurrent complicated acute rhinosinusitis and COVID-19 appear to have higher rates of surgical requirement in the pediatric population. COVID-19 safety precautions have influenced management practices for patients with severe bacterial rhinologic infections. While there may be an association between complicated bacterial rhinosinusitis and COVID-19 infection, further research is necessary to determine a true correlation.

The Role of Seawater and Saline Solutions in Treatment of Upper Respiratory Conditions.

The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and gaining a foothold in the west at the beginning of the 20th century. Today, there is a growing number of papers covering the effects of SNI, from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in the treatment of numerous conditions of the upper respiratory tract (URT), primarily chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in the prevention of viral and bacterial infections of the URT. In this review we discuss results published in the past years focusing on seawater preparations and their use in clinical and everyday conditions, since such products provide the benefits of additional ions vs. saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.

Survey of nebulizer therapy for nasal inflammatory diseases in Japan before and during the COVID-19 pandemic.

OBJECTIVE: Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used vary among regions and according to doctors' preferences. In this study, we aimed to investigate the use of nebulizer therapy for rhinosinusitis. Administration of nebulizer therapy has been affected by the coronavirus disease 2019 (COVID-19) pandemic. Thus, we also investigated the difference in the prevalence of nebulizer use before and during the pandemic. METHODS: Between February and September 2016 and in January 2021, we administered questionnaire surveys on nebulizer treatment for rhinosinusitis to otorhinolaryngologists, who were members of the Oto-Rhino-Laryngological Society of Japan, in Aomori, Saitama, Mie, Fukui, Shiga, Okayama, and Kagoshima prefectures. RESULTS: More than 90% of the otorhinolaryngologists performed nebulizer treatment for rhinosinusitis in 2016. In April 2020 (the first wave of the COVID-19 pandemic), the use rate decreased to 20%, but in January 2021, the use rate increased to 60%. Jet nebulizers were the most frequently used type. One-third of the otolaryngologists enlarged the natural opening of the paranasal sinuses in more than half of their patients by using vasoconstrictors. Cefmenoxime and betamethasone were the most commonly used antibiotics and steroids, respectively. CONCLUSION: Because it is important to perform nasal pretreatment and strict disinfection of nebulizer equipment, it is clear that education of otorhinolaryngologists as well as paramedical personnel is required to ensure safe and effective use of nebulizer therapy in Japan.

Acute Invasive Fungal Rhinosinusitis and Coronavirus Disease 2019.

ABSTRACT: Acute invasive fungal rhinosinusitis (mucormycosis) is a rare, highly fatal disease. This opportunistic fungal infection causes angioinvasion and ischemic tissue necrosis. It mainly affects immunocompromised patients. Since the coronavirus disease 2019 (COVID-19) outbreak, many case reports have described the rhino-orbital-cerebral mucormycosis associated with COVID-19. However, the underlying predisposing factors are unknown. Several factors, other than diabetes, which is the most well-known contributing factor, may be involved in causing this severe fungal infection in COVID-19 patients. These factors may include steroid therapy, which is being used in severely dyspneic patients, the use of broad-spectrum antibiotics that may cause fungal flare-ups, and hospitalization with possible nosocomial infections. In addition, increased serum ferritin levels, possible endothelial damage, and pancreatic islets affection among COVID-19 patients may be implicated. Head and neck surgeons should be aware of the increasing prevalence of craniofacial mucormycosis among COVID-19 patients, as early diagnosis and prompt treatment are essential to improve the outcomes.

Longitudinal saliva omics responses to immune perturbation: a case study.

Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over three periods (100 timepoints) involving: (1) hourly sampling over 24 h without intervention, (2) hourly sampling over 24 h including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (3) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome, and small RNA from salivary extracellular vesicles were profiled, including mRNA, miRNA, piRNA and bacterial RNA. The two 24-h periods were used in a paired analysis to remove daily variation and reveal vaccination responses. Over 18,000 omics longitudinal series had statistically significant temporal trends compared to a healthy baseline. Various immune response and regulation pathways were activated following vaccination, including interferon and cytokine signaling, and MHC antigen presentation. Immune response timeframes were concordant with innate and adaptive immunity development, and coincided with vaccination and reported fever. Overall, mRNA results appeared more specific and sensitive (timewise) to vaccination compared to other omics. The results suggest saliva omics can be consistently assessed for non-invasive personalized monitoring and immune response diagnostics.

Risk of COVID-19 Infection Among Chronic Rhinosinusitis Patients Receiving Oral Corticosteroids.

Chronic rhinosinusitis (CRS) management frequently comprises conservative treatment, including a combination of topical and oral corticosteroids (OCSs). However, in the midst of the coronavirus disease 2019 (COVID-19) pandemic, providers may have been reluctant to prescribe OCSs out of possible concern for an increased risk of contracting COVID-19 or developing more severe COVID-19 symptoms. This study thus sought to explore the association between the use of OCSs and the development of COVID-19 in patients with CRS. We found no statistically significant difference in the rates of patients with a positive diagnosis of COVID-19 who underwent an OCS treatment regimen compared to those who did not, both within 28 days (P = .389) and 14 days (P = .676) prior to the COVID-19 test. Given OCSs are often a major component of medical management of CRS, this study proves helpful in counseling patients on risks of steroid use in CRS treatment during the COVID-19 pandemic.

High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis: A Randomized Clinical Trial.

Importance: Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. Objective: To confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults. Design, Setting, and Participants: This double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines. Interventions: Amoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days. Main Outcomes and Measures: The primary efficacy outcome was a global rating of "a lot better" or "no symptoms" at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment. Results: At an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of "a lot better" or "no symptoms," as did 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%; P = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively. Conclusions and Relevance: The results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate. Trial Registration: ClinicalTrials.gov Identifier: NCT03431337.

Antibiotic Prescribing for Acute Rhinosinusitis: In-Person Versus Virtual Visits During Covid-19.

OBJECTIVES/HYPOTHESIS: Determine if antibiotic prescribing patterns differ for in-person versus virtual clinic visits for acute rhinosinusitis (ARS). STUDY DESIGN: Cross sectional study. METHODS: All adult virtual clinical encounters from March to May 2020 with a principal diagnosis of ARS were reviewed for demographic data and the presence or absence of an antibiotic prescription during the coronavirus shut down in Massachusetts. In-person clinical encounters from March to May 2019 were similarly examined as a control. The rate of antibiotic prescription was compared between virtual (2020) and in-person (2019) visits for ARS diagnoses. RESULTS: There were 2,075 patients in March to May 2020 and 3,654 patients March to May 2019 who received an ARS principal diagnosis at their virtual and in-person outpatient visits, respectively. There was a statistically significant lower rate of antibiotic prescriptions for ARS in 2020 (72.1%) versus 2019 (76.7%).The odds ratio for an antibiotic prescription for ARS was 0.783 (95% confidence interval, 0.693-0.86; P < .001) for patients seen in the 2020 cohort versus the 2019 cohort. The compared rates for antibiotic prescribing for 2020 versus 2019 were not different in individual month-to-month comparisons. When stratified by otolaryngology providers there was no statistically significant difference of antibiotic prescriptions between the 2019 and 2020 cohort (P = .781). CONCLUSIONS: During the massive transition to virtual visits for March to May 2020 due to the coronavirus pandemic shut down in Massachusetts, the total rate of outpatient antibiotic prescribing for ARS was lower in the virtual visit environment compared to the traditional in-person visit. In this scenario, telemedicine did not result in an increase in antibiotic prescribing despite the lack of an in-person physical exam. LEVEL OF EVIDENCE: IV Laryngoscope, 131:E2121-E2124, 2021.

Management of patients with chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position paper.

BACKGROUND: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. METHODS: The current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. RESULTS: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. CONCLUSION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.

Sinusitis caused by a rare organism, Cedecea lapagei.

A 45-year-old man presented with acute sinusitis. He was treated with a 10-day course of trimethoprim/sulfamethoxazole, and a subsequent 14-day course of amoxicillin-clavulanate with no improvement in symptoms. Culture of purulent nasal secretions revealed the rare enterobacter Cedecea lapagei The patient had complete resolution of his symptoms after a 14-day course of gentamicin/dexamethasone nasal rinses. Emerging pathogens have been a timeless concern for physicians, as witnessed by the current SARS-CoV-2 outbreak. C. lapagei has been reported to cause human infection only a dozen times since its discovery, all in severely compromised patients. This is the first documented case of sinusitis reported with C. lapagei and may portend a rising prevalence of disease burden in the general population. This case demonstrates the necessity of obtaining cultures when standard antibiotics result in treatment failure.

Tolerability and effectiveness of povidone-iodine or mupirocin versus saline sinus irrigations for chronic rhinosinusitis.

OBJECTIVES: The role of topical anti-infectives in acute exacerbations of chronic rhinosinusitis is controversial. Povidone-iodine is an anti-bacterial and anti-viral that is affordable and available over-the-counter and may demonstrate advantages over mupirocin as a sinus irrigation therapy. The objective was to compare povidone-iodine or mupirocin versus saline sinus irrigations for sinusitis exacerbations in post-surgery subjects as well as to assess tolerability of povidone-iodine sinus irrigations. MATERIALS AND METHODS: This was a prospective single-blinded (clinician only) randomized controlled trial. Subjects were post-surgery with acute exacerbations of chronic rhinosinusitis and gram-positive bacteria on culture. They received povidone-iodine, mupirocin, or saline sinus irrigations, twice daily for 30 days. Outcomes were post-treatment culture negativity (primary) and Sinonasal Outcome Test-20 and Lund-Kennedy endoscopic score change (secondary). RESULTS: Of the 62 subjects analyzed, post-treatment culture negativity rate was higher in the MUP (14/20, 70%) group compared to the PI (9/21, 43%) and SAL (9/19, 47%) groups, although this was not significant (p = 0.29). Povidone-iodine sinus irrigations at the 1% concentration were very well-tolerated, similar to saline irrigations. There were no significant differences in Sinonasal Outcome Test-20 score (povidone-iodine -0.3 [-0.6, 0.05] vs. mupirocin -0.3 [-0.7, 0.05] vs. saline -0.4 [-0.8, 0.05]; p = 0.86) or Lund-Kennedy endoscopic score (povidone-iodine -3.5 [-7, -0.5] vs. mupirocin -2 [-4, 2] vs. saline -3 [-5, 0]; p = 0.45) change. No serious adverse effects were reported. CONCLUSIONS: In patients who have had prior sinus surgery with acute exacerbations of CRS and gram-positive bacteria on culture, mupirocin sinus irrigations achieved a better post-treatment culture "control" rate compared to saline and povidone-iodine. In addition, 1% povidone-iodine solution was well-tolerated as a sinus irrigation and may represent a feasible method for temporarily disinfecting the sinonasal cavity of bacteria and viruses such as COVID-19.