Targeted next-generation sequencing of pathogens reveals the profile of secondary infections in COVID-19 patients (preprint)

PURPOSE: To use targeted next-generation sequencing (tNGS) of pathogens for analysing the etiological distribution of secondary infections in patients with severe and critical novel coronavirus pneumonia (COVID-19), to obtain microbial epidemiological data on secondary infections in patients with COVID-19, and to provide a reference for early empirical antibiotic treatment of such patients. METHODS: Patients with infections secondary to severe and critical COVID-19 and hospitalised at the First Affiliated Hospital of Shandong First Medical University between 1 December 2022 and 30 June 2023 were included in the study. The characteristics and etiological distribution of secondary infections in these patients were analysed using tNGS. RESULTS: A total of 95 patients with COVID-19 secondary infections were included in the study, of whom 87.37% had one or more underlying diseases. Forty-eight pathogens were detected, the most common being HSV-4, Candida albicans, Klebsiella pneumoniae, Enterococcus faecium, HSV-1, Staphylococcus aureus, Aspergillus fumigatus, Acinetobacter baumannii, HSV-5, and Stenotrophomonas maltophilia, with Pneumocystis jirovecii being detected in 14.29% of cases. The majority (76.84%) of COVID-19 secondary infections were mixed infections, with mixed viral-bacterial-fungal infections being the most common (28.42%). CONCLUSION: Most secondary infections in severe and critical COVID-19 patients are mixed, with high rates of viral and fungal infections. In clinical settings, monitoring for reactivation or secondary infections by Herpesviridae viruses is crucial; additionally, these patients have a significantly higher rate of P. jirovecii infection. tNGS testing on bronchoalveolar lavage fluid can help determine the aetiology of secondary infections early in COVID-19 patients and assist in choosing appropriate antibiotics.

Coronavirus Disease 2019 Combined with T. marneffei Infection Complicated by Undiagnosed HIV：A case report and literature review (preprint)

Background: Talaromycosis(TSM) commonly occurs in immunodeficient or immunosuppressed individuals, but it can also occur in healthy populations. The present case reports the COVID-19 together with human immunodeficiency virus(HIV) and TSM. Case Presentation: This report describes a 26-year-old male who presented with a fever and cough for 20 days. He was diagnosed with COVID-19 and viral pneumonia through a real-time RT-PCR assay and chest CT scan. However, his symptoms failed to improve significantly despite being treated with high-flow oxygen, levofloxacin antibiotic, and dexamethasone for 5 days. The presence of white streaks in his oral cavity, combined with the patient's history of multiple antibiotics, raised the possibility of a fungal infection. The results of the oral pharyngeal swabs indicated that he was infected with T. marnefii, which led to testing for HIV and eventually confirmed the diagnosis. Conclusion: This case demonstrates the importance of being alert to concurrent fungal infections when infecting with COVID-19 and using multiple antimicrobial agents. Additionally, when infecting with T. marnefii, it is crucial to focus on the presence of HIV infection.

Screening of Candida spp. in wastewater in Brazil: Workflow for monitoring as strategy of One Health approach (preprint)

The increase in global temperature, caused by the release of greenhouse gases, favors the pathogenic potential of fungi that, by adapting to higher temperatures in the environment, developed tolerance to the temperatures of mammals. Fungal diseases are frequently associated to poverty and, consequently, precarious conditions of hygiene and sanitation, extremely impaired by COVID-19 pandemics. Additionally, COVID-19 patients can develop a diffuse alveolar damage with severe inflammatory exudation. Dexamethasone, a corticosteroid largely used in the treatment of COVID-19, promotes an immunosuppression profile that facilitates the infection by opportunistic fungi, as Candida spp. In this work, we analyzed the prevalence of Candida yeasts in wastewater samples collected for tracking viral genetical material during COVID-19 pandemic. For this, yeasts obtained were identified by polyphasic taxonomy. Subsequently, the production of biofilm and hydrolytic enzymes, which are well-known virulence attributes, were investigated. Our results showed that all Candida spp. were able to form biofilm and had moderate activity to produce hydrolytic enzymes. We also proposed a workflow for monitoring wastewater with the use of Colony PCR in instead of conventional PCR, since this technique is fast, cheap inexpensive and reliable, improving an accurate on taxonomy identification of yeast in environmental samples, contributing to environmental monitoring as part of the One Health approach.

Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes (preprint)

Cryptococcosis is an invasive fungal infection that typically affects immunocompromised individuals. There is limited research comparing the incidence and clinical outcomes of cryptococcosis in immunocompetent versus immunocompromised patients. Retrospective analysis was performed on patients with a confirmed positive CSF PCR, CSF antigen, or serum cryptococcal antigen tests from 5 hospitals in New York from 2017–2022. Patients were classified as immunocompromised if they had a diagnosis of HIV or active cancer, received an organ transplant, or were on immunosuppressive medications at the time of diagnosis. Baseline demographic information, comorbidities, and clinical outcomes were analyzed. 29 cases of cryptococcosis were identified with 8 cases (27.6%) occurring in immunocompetent patients. Immunocompetent patients with cryptococcosis were more likely to have a prior history of cardiac disease compared to immunocompromised patients (25% vs. 4.76%, p = 0.02). After the beginning of the COVID-19 pandemic, the proportion of immunocompetent cases increased (12% vs 35%, p = 0.03). Despite presenting with meningitis more frequently (75% vs 47.6% p = 0.08), immunocompetent patients demonstrated decreased rates of fungemia (25% vs. 33.3%, p = 0.06) and a significant decrease in mortality (12.5% vs. 23.8%, p = 0.04). Immunocompetent patients presented with meningitis more frequently and demonstrated better outcomes with decreased mortality. The proportion of immunocompetent patients increased over the study period after the beginning of the COVID-19 pandemic. Additional information about cryptococcosis in immunocompetent patients, as well as the role of cardiac disease, diabetes and COVID-19 infection as potential risk factors, warrants further study. Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes

Fungal pleural infection due to Microascus gracilis with pulmonary aspergillosis after COVID-19 pneumonia (preprint)

Background: Scopulariopsis/Microascus is a rare but devastating pathogen due to its intrinsic resistance to nearly all available antifungal agents. Microascus gracilis, an ascomycetous mould in the order Microascales, family Microascaceae, has recently emerged as a significant invasive pathogen causing opportunistic infections. Objectives and Methods: We present a case of pleural infection caused by M. gracilis with pulmonary aspergillosis in an immunocompromised man after COVID-19 pneumonia. To further understand the characteristics of the pathogen isolated from the patient, we identified the strain through mycological characteristics, matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS)-based sequencing, and performed in vitro drug susceptibility testing against common antifungal agents. Moreover, we assessed lymphocyte subsets and programmed cell death protein 1 (PD-1) expression in peripheral blood and pleural effusion to monitor the efficacy of therapy with thymosin-α-1 and intravenous immunoglobulin. Results: Filamentous fungi isolated from pleural fluid were identified as M. gracilis based on classical morphology, mass spectrometry and molecular biology methods. The susceptibility results in vitro revealed that multiple antifungal agents were inactive against the strain. Adjuvant immunomodulatory treatment successfully increased the levels of CD3+ T and CD4+ T cells while decreasing the levels of CD3+PD-1+ and CD4+PD-1+ T cells in both peripheral blood and pleural effusion. Conclusions: The immunocompromised host with opportunistic M. gracilis infection, rapid and accurate recognition through direct microscopic testing with calcofluor white and MOLDI-TOF MS, is the key to achieving a definite diagnosis, and a combination of antifungal therapy with immunomodulatory therapy is vital for improving survival.

COVID-19 Caused by the Omicron Variant in Lung Transplant Recipients: A Single Center Case Series (preprint)

Background: Limited data from the Chinese experience are available regarding the infection status, clinical characteristics, treatments and early outcomes of lung transplant recipients (LTRs) afflicted with coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 Omicron Variant. Methods: We conducted a study on LTRs with COVID-19 caused by the Omicron Variant from November 17, 2022, to May 1, 2023. Clinical information was gathered through electronic medical records, questionnaires, or follow-up telephone calls. To identify potential risk factors for severe disease progression, a multivariate logistic analysis was performed. Results: 178 LTRs with COVID-19 were included, with 50% (89/178) requiring hospitalization for an average stay of 16 days (IQR: 9.5-25.5 days). The most common symptoms were fever (79.8%), dry cough (75.3%) and fatigue (61.8%). Ultimately, 17 recipients succumbed to COVID-19-related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 9.6%. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the Severe/Critical Group (S/C group), while the remaining 58.4% (52/89) had mild to moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher CRP (59.6 vs. 16.8 mg/L, P＜0.01), ESR (45.5 vs. 22.5mm/h, P＜0.01) and D-dimer (1.09 vs. 0.65 mg/L, P＜0.05), but lower CD3+ T lymphocytes (577 vs. 962 cells/ul, P＜0.01) and CD4+ T lymphocytes (217 vs. 427 cells/ul, P＜0.01). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P＜0.01) and pulmonary fungal infection (73.0% vs. 38.5%, P＜0.01) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8mg/L), combined pulmonary fungal infection, and interstitial lung disease(ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective OR values of 4.23 (95% CI: 1.68-11.23), 4.76 (95% CI: 1.59-15.64), and 5.13 (95% CI: 1.19-29.17). Conclusions: LTRs displayed an increased vulnerability to combined lung bacterial or fungal infections following Omicron infection. CRP> 41.8mg/L, ILD as primary disease, and combined pulmonary fungal infection are high-risk factors for developing severe disease.

Changes in respiratory infection trends during the COVID-19 pandemic in the haematologic malignancy patients (preprint)

Background: The coronavirus disease 2019 (COVID-19) pandemic globally changed respiratory infection patterns. However, its impact on community-acquired pneumonia (CAP) in high risk patients with haematological malignancies (HM) is uncertain. We aimed to examine CAP aetiology changes in patients with HM pre- and post-COVID-19 pandemic. Methods: This retrospective study included 524 HM patients hospitalised with CAP between March 2018 and February 2022. Those who underwent bronchoscopy within 24 hours after admission to identify CAP aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and PCR tests were analysed to compare etiological changes and identify in-hospital mortality risk factors. Results: Patients were divided into pre-COVID-19 (44.5%) and post-COVID-19 (55.5%) groups. This study found a significant decrease in viral CAP in the post-COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (3.0% vs. 0.3%, respectively, P = 0.036; 6.5% vs. 0.7%, respectively, P = 0.001; 5.6% vs. 1.4%, respectively, P = 0.015; 9.5% vs. 1.7%, respectively, P < 0.001). Bacterial, fungal, and unknown CAP aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet count correlated with in-hospital mortality after adjusting for potential confounding factors. Conclusion: The incidence of CAP in HM patients did not decrease after COVID-19. Additionally, CAP aetiology among patients with HM changed following the COVID-19 pandemic, with a significant reduction in viral pneumonia while bacterial and fungal pneumonia persisted. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with HM and CAP.

Hospital-treated serious and invasive aspergillosis and candidiasis infections during the COVID-19 pandemic: a retrospective analysis of Hospital Episode Statistics data from England.

OBJECTIVES: To investigate the impact of COVID-19 on the burden of hospital-treated Aspergillus and Candida infections in England. DESIGN: A retrospective study using Hospital Episodes Statistics data to estimate the burden of serious and invasive fungal infections (SIFIs) in all patients admitted in England during March 2018-February 2020 (pre-COVID-19) and during March 2020-October 2021 (the COVID-19 period). SETTING: Hospitals in England. POPULATION: All patients with codes corresponding to serious and invasive aspergillosis and candidiasis in any diagnosis position during their admission pre-COVID-19 and during the COVID-19 period. OUTCOME MEASURES: Age, spells, patient counts, mean length of stay, admission to critical care unit (CCU), length of stay in CCU, 30-day readmissions, failed discharges (readmission within 7 days) and comorbidities. RESULTS: During the COVID-19 period, hospitalisation spells with an invasive candidiasis code fell by 3.2% and spells with an aspergillosis code by 24.8%. Mean length of stay was higher for patients with aspergillosis with or without COVID-19 and candidiasis with or without COVID-19 during the pandemic than before the pandemic. During the pandemic, mean length of stay was higher for patients with aspergillosis with COVID-19 than those with aspergillosis alone but slightly lower for patients with candidiasis with COVID-19 than for those with candidiasis alone. Of patients with a diagnosis of COVID-19, 52.5% with aspergillosis and 60.0% with candidiasis were treated in CCU compared with 13.2% and 37.1%, respectively, without a COVID-19 diagnosis. The percentage of 30-day readmissions and failed discharges for patients with SIFI was higher for those with COVID-19 than for those without. CONCLUSIONS: The burden of aspergillosis and candidiasis has been affected by COVID-19. Aspergillosis diagnoses fell among hospitalised patients during the pandemic, while candidiasis continued to fluctuate in patterns similar to pre-COVID-19. A higher burden for patients with SIFI was observed, whether or not they also had a diagnosis of COVID-19. Our findings highlight extra considerations and burden on management of serious SIFI as a result of the COVID-19 pandemic.

Mycobiome analyses of critically ill COVID-19 patients suggests antifungal prophylaxis may be protective against A. fumigatus-associated mortality (preprint)

Rationale: Covid-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID -19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and Candida colonisation. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality. However, specific mycobiome signatures associated with severe COVID-19 in the context of survival and antifungal drug prophylaxis have not yet been determined and such knowledge could have an important impact on treatment. Objectives: To understand the composition of the respiratory mycobiome in critically ill COVID -19 patients with and without CAPA, the impact of antifungal use and its role in patient outcome. Methods: We performed a multi-national study of 39 COVID-19 patients in intensive care units (ICU) with and without CAPA. Respiratory mycobiome was profiled using ITS1 sequencing and Aspergillus fumigatus burden was further validated using qPCR. Fungal communities were investigated using alpha diversity, beta diversity, taxa prevalence and taxa abundances. Measurements and Main Results: Respiratory mycobiomes were dominated by Candida and Aspergillus. There was no significant association with corticosteroid use or CAPA diagnosis and respiratory fungal communities. Increased A. fumigatus burden was associated with mortality. The use of antifungals at ICU admission was associated with an absence of A. fumigatus. Conclusions: Our findings suggest that systemic antifungal treatment at ICU admission may be protective against A. fumigatus-associated mortality in CAPA.

Liposomal amphotericin B-the future.

Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.

The Impact of COVID-19 on the Epidemiology and Outcomes of Candidemia: A Retrospective Study from a Tertiary Care Center in Lebanon (preprint)

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19 associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4% respectively). Mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported mortality of candidemia from previous studies at our center. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs 78.1%; P =0.76). Performing ophthalmic examination (P = 0.002), CVC removal during the 48 hours following the candidemia (P = 0.008) and identifying the Candida spp. (P = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species like C. auris.

Ramification of COVID-19 pandemic : Occurrence and impact of fungal infections in a tertiary care hospital (preprint)

Coronavirus disease 2019 (COVID-19) pandemic has been prevailing for more than a year associated with increased number of opportunistic invasive fungal infections in patients who have been critically ill or immunocompromised. In this retrospective study, details of various clinical specimens received from suspected patients of fungal infections were processed according to standard protocol were studied. The fungal infections were present in 64% (51/79) COVID-19 positive patients and 43% (163/381) COVID-19 negative patients) during the year 2021 during the second wave of COVID-19. Among COVID-19 infected patients, the fungal infection mostly observed was Candidiasis (63%) followed by Aspergillosis (15% ) and Mucormycosis (6%). The maximum samples positive in COVID-19 patients were urine samples followed by Serum (for Aspergillus Galactomannan). Among the urine and respiratory samples (BAL, Tracheal aspirate, Sputum) in COVID-19 positive patients, maximum positivity of Candida species was seen. Mucormycosis in COVID-19 positive patients was isolated in Nasal samples followed by tissue sample with Rhizopus arrhizus and Rhizopus homothallicus. There has been an increase in fungal co-infections during the COVID-19 pandemic which is a matter of great concern. Early diagnosis is essential for effective management of these patients.

Fungal infection profile in critically ill COVID-19 patients: a prospective study at a large teaching hospital in a middle-income country.

BACKGROUND: Critically ill COVID-19 patients are highly susceptible to opportunistic fungal infection due to many factors, including virus-induced immune dysregulation, host-related comorbidities, overuse and misuse of antibiotics or corticosteroids, immune modulator drugs, and the emergencies caused by the pandemic. This study aimed to assess the incidence, identify the potential risk factors, and examine the impact of fungal coinfection on the outcomes of COVID-19 patients admitted to the intensive care unit (ICU). METHODS: A prospective cohort study including 253 critically ill COVID-19 patients aged 18 years or older admitted to the isolation ICU of Zagazig University Hospitals over a 4-month period from May 2021 to August 2021 was conducted. The detection of a fungal infection was carried out. RESULTS: Eighty-three (83) patients (32.8%) were diagnosed with a fungal coinfection. Candida was the most frequently isolated fungus in 61 (24.1%) of 253 critically ill COVID-19 patients, followed by molds, which included Aspergillus 11 (4.3%) and mucormycosis in five patients (1.97%), and six patients (2.4%) diagnosed with other rare fungi. Poor diabetic control, prolonged or high-dose steroids, and multiple comorbidities were all possible risk factors for fungal coinfection [OR (95% CI) = 10.21 (3.43-30.39), 14.1 (5.67-35.10), 14.57 (5.83-33.78), and 4.57 (1.83-14.88), respectively]. CONCLUSION: Fungal coinfection is a common complication of critically ill COVID-19 patients admitted to the ICU. Candidiasis, aspergillosis, and mucormycosis are the most common COVID-19-associated fungal infections and have a great impact on mortality rates.

Cryptococcus neoformans, a global threat to human health.

BACKGROUND: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. METHODS: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. RESULTS: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. CONCLUSION: The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

Immunity to fungi in the lung.

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.

Virus-associated fungal infections and lost immune resistance.

Invasive fungal infections are an increasing threat to human health. Of recent concern is the emergence of influenza- or SARS-CoV-2-virus-associated invasive fungal infections. Understanding acquired susceptibilities to fungi requires consideration of the collective and newly explored roles of adaptive, innate, and natural immunity. Neutrophils are known to provide host resistance, but new concepts are emerging that implicate innate antibodies, the actions of specialized B1 B cell subsets, and B cell-neutrophil crosstalk in mediating antifungal host resistance. Based on emerging evidence, we propose that virus infections impact on neutrophil and innate B cell resistance against fungi, leading to invasive infections. These concepts provide novel approaches to developing candidate therapeutics with the aim of restoring natural and humoral immunity and boosting neutrophil resistance against fungi.

Ayurveda management of pulmonary mycosis: an integrative approach: a case report.

BACKGROUND: Pulmonary mycosis is a fungal infection of the lung. Antifungal treatments are used in conventional treatments; however, incomplete response and toxicity are major challenges of antifungal therapies. In Ayurveda, pulmonary mycosis is diagnosed and treated based on principles of respiratory disorders (referred to as Shvaas Roga) with promising outcomes. CASE PRESENTATION: A > 60-year-old South Indian male patient visited Institute of Ayurveda and Integrative Medicine with complaints of cough, breathlessness, pedal edema, weight loss, uncontrolled diabetes, and anemia. Following chest X-ray, high-resolution computed tomography (HRCT) and bronchoscopy, the patient was diagnosed with a case of pulmonary mucormycosis. The patient had availed conventional allopathic treatment for 3 months including standard antifungal medication for 3 weeks. However, due to unresolved and persistent symptoms, the patient sought Ayurveda treatment. The patient was diagnosed and treated for 6 weeks as a case of Shvaasa Roga, a subcategory of the respiratory disorder according to Ayurveda, and was cured of the infection following an integrative Ayurveda management regime which included internal medicines, panchakarma, necessary poorvakarmas (like abhyanga and swedhana), diet and lifestyle advice, yoga and acupuncture. CONCLUSIONS: The patient was cured of fungal lung infection in 6 weeks using an integrative approach. Primary Ayurveda treatment supported with diet and lifestyle modifications, yoga, and acupuncture helped the patient to recover from illness. The patient is alive and free of disease for more than one year to date.

Assessing compliance of infection prevention mitigation strategies in hospital construction and renovation.

Hospital-associated fungal infections from construction and renovation activities can be mitigated using an infection control risk assessment (ICRA) and implementation of infection prevention measures. The effectiveness of these measures depends on proper installation and maintenance. Consistent infection prevention construction rounding with feedback is key to ongoing compliance.

Is low dose of liposomal amphotericin B effective in management of acute invasive fungal rhinosinusitis? Our conclusions from Al-Mowassat University Hospital, Syria: a prospective observational study.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is a fatal infection associated with high morbidity and mortality. Although it is a rare disease, upsurge of AIFRS was noticed during the second wave of COVID-19 disease. Early diagnosis and management is the cornerstone for good outcomes. However, management of AIFRS is challengeable especially in developing countries due to limited resources and high prices of antifungal agents. No previous studies have been conducted to evaluate the outcomes of management of AIFRS in Syria. The purpose of this study is to report the results of management of AIFRS with low doses of liposomal amphotericin B in our tertiary hospital in Syria. METHODS: The outcomes of management of AIFRS cases were followed through a prospective observational study between January 2021 and July 2022. The required medical data were collected for each individual. Three-month mortality rate was studied. SPSS v.26 was used to perform the statistical analysis. Pearson Chi-square test was used to study the associations between different variables and mortality. Survival curves were plotted by the Kaplan-Meier to compare the survival probability. Log Rank (Mantel-Cox) test and Cox regression were conducted to evaluate the factors affecting survival within the follow up period. RESULTS: Of 70 cases, 36 (51.4%) were males and 34 (48.6%) were females. The mean age of patients was 52.5 years old. The most common underlying risk factor was diabetes mellitus (84.3%). The used dose of liposomal amphotericin B ranged between 2-3 mg/kg per day. The overall 3-month mortality rate was 35.7%. Significant association was found between survival and the following variables: Age, orbital involvement, stage, and comorbidity. CONCLUSION: The overall mortality rate was close to other studies. However, survival rate was worse than comparable studies in selected cases of AIFRS (older ages, involved orbits, advanced stages, and chronic immunodeficiency). Therefore, low doses of liposomal amphotericin B could be less effective in such cases and high doses are recommended.