The challenges of the genome-based identification of antifungal resistance in the clinical routine.

The increasing number of chronic and life-threatening infections caused by antimicrobial resistant fungal isolates is of critical concern. Low DNA sequencing cost may facilitate the identification of the genomic profile leading to resistance, the resistome, to rationally optimize the design of antifungal therapies. However, compared to bacteria, initiatives for resistome detection in eukaryotic pathogens are underdeveloped. Firstly, reported mutations in antifungal targets leading to reduced susceptibility must be extensively collected from the literature to generate comprehensive databases. This information should be complemented with specific laboratory screenings to detect the highest number possible of relevant genetic changes in primary targets and associations between resistance and other genomic markers. Strikingly, some drug resistant strains experience high-level genetic changes such as ploidy variation as much as duplications and reorganizations of specific chromosomes. Such variations involve allelic dominance, gene dosage increments and target expression regime effects that should be explicitly parameterized in antifungal resistome prediction algorithms. Clinical data indicate that predictors need to consider the precise pathogen species and drug levels of detail, instead of just genus and drug class. The concomitant needs for mutation accuracy and assembly quality assurance suggest hybrid sequencing approaches involving third-generation methods will be utilized. Moreover, fatal fast infections, like fungemia and meningitis, will further require both sequencing and analysis facilities are available in-house. Altogether, the complex nature of antifungal resistance demands extensive sequencing, data acquisition and processing, bioinformatic analysis pipelines, and standard protocols to be accomplished prior to genome-based protocols are applied in the clinical setting.

Cryptococcal meningitis post-covid-19 infection: Immunomodulation, a double-edged sword.

Cryptococcal meningitis is an opportunistic infection associated with altered immunity. Immunomodulatory agent use in severe coronavirus disease 2019 (COVID-19) may predispose such infections. Here, we present a 75-year-old male patient who presented with fever and altered general status after severe COVID-19 infection and developed cryptococcal meningitis. Opportunistic infection may arise from the use of immunomodulation in severe COVID-19, especially in the elderly population. This article describes the case and extensively reviews cryptococcal disease post-COVID-19 literature, highlighting the risk from immunosuppressive treatment.

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

A Possible New Diagnostic Method for Early Diagnosis of Cryptococcus Infection in Lymphoma Patient Co-Infected with SARS-CoV-2

A Cryptococcus subspecies, neoformans, represents the most pathogenic infection for humans, particularly in immunocompromised hosts (e.g., cancer patients, drug users). In the present study, we described a 67-year old woman with non-Hodgkin lymphoma who developed an infectious disease sustained by Cryptococcus neoformans. Biochemical data documented a decrease in lymphocytes count while clinical evaluation was suggestive on meningeal infection. The microbiological analysis of the serum, using a dilution pattern through the CrAg lateral flow assay (Immy, Norman, OK 73069, USA) detected the antigen of Cryptococcus (dilution 1/1280), and a treatment with liposomal amphotericin B (3 mg/kg id) plus flucytosine (100 mg/kg per day orally in four divided doses) were started, showing an improvement of symptoms. This case report suggests that an antigen dilution can be used to perform a rapid diagnosis and to quickly start the pharmacological treatment.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Fungal infection: An unrecognized threat

The fungi are eukaryotes and of great interest to microbiologist. Fungi are heterotrophic organism that require organic compounds for nutrition. According to Hawksworth, only around 100 fungi cause diseases in humans and animals out of around 1.5 million existing in the universe. Fungal pathogenic infection may cause allergies, superficial infection, as well as invasive mycosis in severe cases. Public health can be significantly affected by zoonotic fungi that transmit naturally between animals and humans. Prevention of fungal infection arising out of zoonotes has received insufficient attention as it lacks mass awareness. A number of different fungal infections, their signs and symptoms, preventive measures, and treatment protocol are demonstrated in this chapter. Regarding the treatment of various fungal infections, azoles, fluoropyrimidines, polyenes, and echinocandins are the only four molecular classes of drugs available as on date to target fungal metabolic pathways despite years of drug discovery research. Few other promising molecules like morpholines and allylamines are useful antifungal but with poor efficacy and severe side effects when administered systematically. Development of resistance against most common antifungal drugs further aggravates the situation. Fungal infection like mucormycosis is observed in some parts of the world after a patient gets infected with COVID-19 as there is impairment in the immunity system. There is an urgent need to control this fungal infection as it poses serious threat silently. We can limit the spread of fungal infection by protecting susceptible population from being exposed. More efforts are needed from a global health perspective to aware the people regarding neglected fungal infection and its problem so that socioeconomic consequences and mortality can be better explained. An integrated platform of prevention and control strategies for the spread of fungal infection is the need of the hour. © 2023 Elsevier Inc. All rights reserved.

Taking a Break: Host-Fungi in a Distance Relationship

This chapter will explore the main mechanisms used by fungal pathogens to interfere with the optimal immune response developed by the host, focusing mainly on molecules that are freely secreted or encompassed by vesicles. The emphasis will be on two important systemic pathogens: Cryptococcus neoformans and Fonsecea sp. Severe systemic infections caused by fungal pathogens have increased in numbers and clinical importance in the last decades. The rise in immunocompromised individuals is a key factor in this matter, as seen lately in COVID-affected patients receiving immunosuppressive treatment and a higher correlation with fungal infections. Regarding host-pathogen interaction, there is increasing evidence in the literature that shows a vital role of secreted molecules in the course of opportunistic fungal infection. Ultimately, the capacity to externalize potential virulence factors can help the pathogen in several ways, for example evading immune cells, controlling inflammation kinetics, and enhancing dissemination into deeper tissues. © 2023 Nova Science Publishers, Inc.

Differentiating infectious from non-infectious respiratory disease in the cat and dog

This paper describes the clinical signs and use of differential laboratory diagnostic techniques (computed tomography, cytology, histopathology, antigen/antibody detection and polymerase chain reaction) for infectious (viral, bacterial, fungal and parasitic) and non-infectious (inflammatory/immune mediated, neoplastic, cardiac, malformation, foreign body, smoke inhalation, aspiration of caustic material, non-cardiogenic, pulmonary oedema, traumativ, pneumothorax, pulmonary contusions and idiopathic) causes of respiratory diseases in cats and dogs in Ontario, Canada.

Invasive fungal infections in COVID-19 patients from Pakistan

Objective: The objective of this study is to report the frequency and clinical characteristic of IFI in COVID-19 patients. Method(s): This observational study was conducted in Karachi, Pakistan from March 2020-April 2021. Patients with COVID-19 associated aspergillosis (CAPA) were diagnosed using ECMM/ISHAM criteria modified to include tracheal aspirate culture and/or Galactomannan Index (GMI) >4.5 in the possible CAPA category. COVID-19 associated candidemia (CAC) was defined by isolation of Candida species from blood cultures. COVID-19 associated mucormycosis (CAM) was defined as updated EORTC/MSG criteria with inclusion of COVID-19 as host factor. Pneumocystis jirovecii pneumonia (PJP) was defined by consistent clinical and radiological features and PCR positivity. Result(s): During the study period a total of 123 (3.3%) IFI in 3506 hospitalized COVID-19 patients were identified. This included 78 (2.2%) CAPA patients (42 probable;36 possible), 29 (0.8%) CAC (5 C. auris;24 non-C. auris), 10 (0.3%) CAM (7 pulmonary;3 rhinocerebral), 3 (0.08%) PJP and three (0.08%) cases of rare invasive fungal infections (2 C. neoformans;1 Trichosporon asahii). Outcome data was available on 117/123 patients. Of these 117 patients, 78 expired (66.7%). These include 52/74 (70%) CAPA patients, 17/27 (63%) CAC patients, 7/10 (70%) CAM patients and 2/3 (67%) PJP patients. Conclusion(s): We report a rate of 3.3% IFI amongst hospitalized COVID-19 patients at our center. We consider this rate to be an underestimate due to less bronchoscopic procedures and inclusion of only candidemia cases. We also report higher mortality rate with IFI in our patients than global data probably due to delayed diagnosis, co-infections and limited therapeutic options.

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.

Cerebral Cryptococcosis Associated with CD4+ T-lymphocytopenia in Non-HIV Patients after SARS-CoV-2 Infection: Case Series in a Specialized Institute in Lima, Peru.

Cases of cryptococcosis have been reported in patients with COVID-19. The majority are in patients with severe symptoms or who received immunosuppressants. However, there is still no clear association between COVID-19 and cryptococcosis. We report eight cases of cerebral cryptococcosis associated with CD4+ T lymphocytopenia in non-HIV patients after SARS-CoV-2 infection. The median age was 57 years and 5/8 were male. In addition, 2/8 of patients had diabetes, and 8/8 had a history of mild COVID-19, with a median of 75 days before diagnosis of cerebral cryptococcosis. All patients denied having received prior immunosuppressive therapy. The most frequent symptoms were confusion (8/8), headache (7/8), vomiting (6/8), and nausea (6/8) All patients were diagnosed by isolating Cryptococcus in cerebrospinal fluid. The median CD4+ and CD8+ T lymphocytes were 247 and 173.5, respectively. Other causes of immunosuppression, such as HIV or HTLV infection, were excluded in all patients. Finally, three patients died, and one presented long-term visual and auditory sequelae. The CD4+/CD8+ T lymphocyte count normalized during follow-up in those patients who survived. We hypothesize that CD4+ T lymphocytopenia in the patients in this case series could increase the risk of cryptococcosis after SARS-CoV-2 infection.

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.

Missed opportunities to identify cryptococcosis in COVID-19 patients: a case report and literature review.

SARS-CoV-2 may activate both innate and adaptive immune responses ultimately leading to a dysregulated immune response prompting the use of immunomodulatory therapy. Although viral pneumonia increases the risk of invasive fungal infections, it remains unclear whether SARS-CoV-2 infection, immunomodulatory therapy, or a combination of both are responsible for the increased recognition of opportunistic infections in COVID-19 patients. Cases of cryptococcosis have previously been reported following treatment with corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors, for patients with autoimmune diseases, but their effect on the immunologic response in patients with COVID-19 remains unknown. Herein, we present the case of a patient with COVID-19 who received high-dose corticosteroids and was later found to have cryptococcosis despite no traditional risk factors. As our case and previous cases of cryptococcosis in patients with COVID-19 demonstrate, clinicians must be suspicious of cryptococcosis in COVID-19 patients who clinically deteriorate following treatment with immunomodulatory therapies.

Characteristics and Outcomes of Cryptococcosis among Patients with and without COVID-19.

The effect of COVID-19 on the risk and prognosis of cryptococcosis is unclear. We compared the characteristics and outcomes of cryptococcosis in patients with and without COVID-19. Patients 18 years and older with cryptococcosis were identified from TriNetX and separated into two cohorts based on a diagnosis of COVID-19 within 3 months of the index diagnosis of cryptococcosis. Differences examined between groups included comorbidities, immunosuppressive medications, ED visits, hospitalizations, ICU admissions, mechanical ventilation, and deaths. The propensity score matching was performed based on demographics and comorbidities. Of the 6998 patients with cryptococcosis included, 4.4% (n = 306) had COVID-19 prior to cryptococcosis. Mortality was higher in patients with COVID-19 compared to those without COVID-19 (14% vs. 11%, p = 0.032). Additionally, those with COVID-19 were older (55.2 ± 14.4 vs. 51.9 ± 15.2 years, p < 0.001) with higher rates of transplant (29% vs. 13%, p < 0.001), neoplastic disease (37% vs. 21%, p < 0.001), chronic kidney disease (42% vs. 18%, p < 0.001), or diabetes (35% vs. 19%, p < 0.001) but not HIV (30% vs. 31%, p = 0.618). Glucocorticoid use was more common in those with COVID-19 (52% vs. 27%, p < 0.001). More patients with COVID-19 required ED visits (29% vs. 23%, p = 0.025) and ICU admission (18% vs. 11%, p < 0.001). After propensity score matching, patients with COVID-19 had higher rates of neoplastic disease, heart failure, chronic kidney disease, and glucocorticoid use but did not experience worse outcomes compared to those without COVID-19. Patients with COVID-19 who developed cryptococcosis had independently higher rates of comorbidities and glucocorticoid use but similar outcomes, including death, versus those without COVID-19.

Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

Cryptococcal chest wall mass and rib osteomyelitis associated with the use of fingolimod: A case report and literature review.

Being introduced in 2010, fingolimod was among the first oral therapies for relapsing multiple sclerosis (MS). Since that time, postmarketing surveillance has noted several case reports of various cryptococcal infections associated with fingolimod use. To date, approximately 15 such case reports have been published. We present the first and unique case of cryptococcal chest wall mass and rib osteomyelitis associated with fingolimod use. The patient presented with left-side chest pain and was found to have a lower left chest wall mass. Computerized tomography (CT) showed chest wall mass with the destruction of left 7th rib. Aspirate from the mass grew Cryptococcus neoformans. The isolate was serotype A. Fingolimod was stopped. The patient received liposomal amphotericin B for 2 weeks and started on fluconazole with a plan to continue for 6-12 months. The follow-up CT in 6 weeks showed a marked decrease in the size of the chest wall mass. In conclusion, our case highlights the atypical and aggressive form of cryptococcal infection possibly related to immunosuppression from fingolimod use.

CRYPTIC CRYPTO: PULMONARY CRYPTOCOCCOSIS IN AN IMMUNOCOMPETENT HOST

SESSION TITLE: Uncommon Presentations and Complications of Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cryptococcus is a ubiquitous fungus in the environment. Infections can occur in humans when Cryptococcus is aerosolized and inhaled. Severity of clinical presentation varies from asymptomatic pulmonary colonization to disseminated life-threatening infection such as meningitis. These infections usually occur with deficiencies in T-cell-mediated immunity, including those with HIV/AIDS and immunosuppression due to transplantation. Herein we present a case of isolated pulmonary cryptococcosis in an immunocompetent host. CASE PRESENTATION: The patient is a 36-year-old never-smoker male with history of recurrent left spontaneous pneumothorax status post VATS blebectomy, negative for alpha-1 antitrypsin deficiency and cystic fibrosis. A year later, he presented with fatigue, shortness of breath, and dry cough after a recent trip to Ohio. Viral panel including COVID-19 was negative. A chest x-ray showed a new 4 cm rounded opacity in the right middle lobe (RML). A CT scan of the chest showed 2 mass-like and nodular areas of consolidation with surrounding GGOs within the RML (Figure 1). He underwent navigational bronchoscopy with transbronchial biopsy (TBBx) of RML, BAL, and EBUS with transbronchial needle aspiration (TBNA). Cytology was negative for malignant cells. BAL showed rare yeast. Pathology of the TBBx showed the airway wall with chronic inflammation including granulomatous inflammation, positive for yeast, most consistent with Cryptococcus with positive Grocott methenamine silver (GMS) stain (Figure 2). Culture of the TBNA grew C. neoformans var. grubii. Other cultures were negative. Serum Cryptococcal antigen was positive. HIV test was negative. He started treatment with oral fluconazole with improvement of symptoms. DISCUSSION: Clinical presentation of pulmonary cryptococcosis can include a variety of symptoms in which immune status is critical for determining the course of infection. Infection can vary from asymptomatic infection to severe pneumonia and respiratory failure, and meningitis. Similarly, imaging findings can also vary and be characterized as pulmonary nodules, consolidations, cavitary lesions, and/or a diffuse interstitial pattern. The diagnosis of Cryptococcus is made using histology, fungal cultures, serum cryptococcal antigen, and radiography in the appropriate clinical and radiological context. Treatment recommendations are determinant on immune status of the patient as well as symptoms. Asymptomatic and localized disease in immunocompetent patients can be monitored and mild/moderate disease can be treated with fluconazole. Those with severe or disseminated infection warrant induction therapy with an amphotericin B and flucytosine CONCLUSIONS: Clinical and radiological presentation of cyptococcosis varies depending on immune status. Disease can occur in both immunocompromised and competent hosts. Immune status determines disease course and treatment. Reference #1: Huffnagle GB, Traynor TR, McDonald RA, Olszewski MA, Lindell DM, Herring AC, et al. Leukocyte recruitment during pulmonary Cryptococcus neoformans infection. Immunopharmacology. 2000 Jul 25;48(3):231–6. Reference #2: Kd B, Jw B, Pg P. Pulmonary cryptococcosis. Semin Respir Crit Care Med [Internet]. 2011 Dec [cited 2022 Apr 2];32(6). Available from: https://pubmed.ncbi.nlm.nih.gov/22167400/ Reference #3: Ms S, Rj G, Ra L, Pg P, Jr P, Wg P, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am [Internet]. 2000 Apr [cited 2022 Apr 1];30(4). Available from: https://pubmed.ncbi.nlm.nih.gov/10770733/ DISCLOSURES: No relevant relationships by Mina Elmiry No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih no disclosure on file for Priyanka Makkar;No relevant relationships by Jonathan Moore

INCIDENCE, CLINICAL CHARACTERISTICS, AND OUTCOMES OF PATIENTS WITH COVID-19 AND FUNGAL COINFECTION

SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: To evaluate the incidence of fungal co-infections clinical characteristics, and outcomes in patients with COVID-19. METHODS: We conducted a retrospective chart review of electronic medical records of 2,639 adult patients admitted for COVID -19 to our health system from April 1, 2020 to December 31, 2021. Demographic data, comorbidities, length of hospital stay, laboratory results including fungal diagnostics, COVID therapeutics and antifungals, need for ICU admission, mechanical ventilation and in-hospital mortality were collected. RESULTS: A total of 45 of 2,639 (1.7%) COVID-19+ patients had a positive fungal test or culture of fungal pathogen and subsequently received antifungal treatment. Of these 25 (55.6%) cases of Aspergillus species were the most prominent, followed by Candida species at 12 (26.7%). Of note, there was one case each of Cryptococcus and Histoplasma (2.2%). COVID-19+ patients with fungal co-infection who survived (18;40%) were significantly younger compared to COVID-19+ patients with fungal co-infection who died (27;60%, p=0.014). Majority of COVID-19+ patients with fungal co-infection were white with average length of hospitalization of 24 days. Those patients who survived had a significantly longer length of hospitalization compared to COVID-19+ patients who died (survived 31 ± 21.5 compared to 19.6 ± 10.4 days, p<0.05). Majority of COVID-19+ patients received steroids, and remdesivir therapy for COVID-19. Antifungal treatment consisted of either voriconazole or micafungin as predominate fungal pathogens were either Aspergillus or Candida spp. CONCLUSIONS: Pulmonary aspergillosis followed by invasive candidiasis were the most common fungal co-infections in COVID-19 patients treated at our institution. In-hospital mortality from all fungal co-infections was 60%. Patients that survived were younger and hospitalized longer compared to those who expired. Need for mechanical ventilation, ICU admission and COVID therapeutics were not significantly different between the survived and expired group of COVID-19 patients with fungal co-infections. CLINICAL IMPLICATIONS: The increased risk and incidence of COVID-19 and fungal co-infection has been noted in a handful of studies with invasive aspergillosis being the most commonly reported fungal co-infection. There have been very few reports of other fungal co-infections including invasive candidiasis, mucormycosis, histoplasmosis, and cryptococcosis. Minimal incidence data has been reported on co-infection with other opportunistic fungal pathogens such as Histoplasma spp., Pneumocystis jirovecci, or Cryptococcus neoformans. This study supports previous findings of increase risk of Aspergillosis, but also show incidence of Histoplasmosis and Crytpococcal fungal infections. These fungal infections may be under reported in COVID-19 and may warrant further research. DISCLOSURES: No relevant relationships by Christopher Destache No relevant relationships by Rutendo Jokomo-Nyakabau No relevant relationships by Dorothy Kenny No relevant relationships by Paul Millner No relevant relationships by Anny Nguyen No relevant relationships by Mohammad Selim No relevant relationships by Richard Swaney No relevant relationships by Manasa Velagapudi

Neuromeningeal cryptococcosis in a patient not infected with human immunodeficiency virus and without known risk factors: A case report.

We report a 24-year-old female patient not infected with human immunodeficiency virus (HIV) and without other risk factors of immunosuppression, presenting with neuromeningeal cryptococcosis. Cerebrospinal fluid (CSF) analysis revealed the presence of Cryptococcus neoformans. The evolution was unfavorable and the patient died even after appropriate antifungal treatment.