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.

Ophthalmic and immunopathological characterization of systemic infectious diseases in cats.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study.

OBJECTIVES: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. METHODS: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/µL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020). RESULTS: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03). DISCUSSION: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.

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.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

Pulmonary Cryptococcosis and Pulmonary Fibrosis: A Complication of COVID-19 Pneumonia.

Acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF) are increasingly identified as complications of coronavirus disease 2019 (COVID-19) infection, the latter being managed with tapering dose glucocorticoids. Studies have shown improved outcomes with steroid use in this subset of patients; however, the use of high doses of steroids predisposes these patients to develop various complications such as opportunistic infections. The incidence of pulmonary cryptococcosis (PC) in patients with post-COVID-19 PF is not known. Here, we discuss a middle-aged male, with no pulmonary comorbidities, who developed PC secondary to the immunocompromised state from high-dose steroid use for the management of post-COVID-19 PF.

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.

Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis.

During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a life-threatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and COVID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead" and "alive". Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (α=0.05). To compare quantitative variables a U Mann-Whitney test was used (α=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead" group, and 15/32 (46.9%) patients survived and were included in "alive" group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53-70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality.

Addressing Microbial Resistance Worldwide: Challenges over Controlling Life-Threatening Fungal Infections.

Fungal infections are a serious global concern because of their ability to spread and colonize host tissues in immunocompromised individuals. Such infections have been frequently reported worldwide and are currently gaining clinical research relevance owing to their resistant character, representing a bottleneck in treating affected people. Resistant fungi are an emergent public health threat. The upsurge of such pathogens has led to new research toward unraveling the destructive potential evoked by these species. Some fungi-grouped into Candida, Aspergillus, and Cryptococcus-are causative agents of severe and systemic infections. They are associated with high mortality rates and have recently been described as sources of coinfection in COVID-hospitalized patients. Despite the efforts to elucidate the challenges of colonization, dissemination, and infection severity, the immunopathogenesis of fungal diseases remains a pivotal characteristic in fungal burden elimination. The struggle between the host immune system and the physiological strategies of the fungi to maintain cellular viability is complex. In this brief review, we highlight the relevance of drug resistance phenotypes in fungi of clinical significance, taking into consideration their physiopathology and how the scientific community could orchestrate their efforts to avoid fungal infection dissemination and deaths.

Outcome of patients with non-COVID-19 related Aspergillosis during the COVID-19 pandemic

Background. In March 2020 our Institution was designated a COVID-19 unit, since the start of 2021 conventional medical attention has been reinstalled and it became a hybrid hospital. Our objective was to compare the outcome of patients with Invasive Aspergillosis (IA) without COVID-19 during the COVID-19 pandemic, compared with past controls from a historical cohort, and describe their clinical characteristics. As a secondary objective, we described the characteristics of other Invasive Fungal Infections (IFI) in a similar patient group. Methods. Retrospective and descriptive study. The information was obtained from the electronic file. For IFI diagnosis, the EORTC/MSG criteria for proven and probable infection were considered, including the AspiCU modified criteria. The main outcome was death at 6 weeks, time from symptom onset to diagnosis/treatment, and having received antifungal treatment as secondary outcomes. Outcomes were compared to historical IA controls (2:1) from a pre-COVID-19 cohort. The study was approved by the local research and ethics committee. Results. From March 2020 to December 2021, 50 IFIs were diagnosed in non-COVID-19 patients, of which 27 (54%) were Invasive Aspergillosis, 10 (20%) Cryptococcosis, 8(16%) histoplasmosis, 4 (8%) mucormycosis, and 1 (2%) Fusariosis. The median age was 44 years (IQR 33-58) and 67% were men. Forty three percent (22/51) had immunosuppression and 35% (18/51) had hematological malignancy, the median time from symptom onset to IFI diagnosis was 30 days (IQR 11-90) and 38% died within 6 weeks. During the pandemic, in Invasive Aspergillosis non COVID-19 patients, the median number of days from symptom onset to start antifungal was 21 (IQR 6-68) vs 5 (IQR 3-10) of IA historic controls (p=0.0005), 81.5% (22/ 27) vs 93% (50/54) received antifungal treatment (OR 0.88 , 95% CI 0.72-1.0, p=0.13), and IA cases had a mortality of 44% (12/27) vs 41% (22/54) in the historical cohort (p=0.75). We show the IA characteristics in Table 1. GM: Galactomannan antigen Conclusion. During the COVID-19 pandemic, patients with IA withouth COVID-19 were diagnosed significantly later. Also, a trend towards increased mortality and lower proportion of antifungal treatment was observed. It is likely a consequence of hospital reconversion during the start of the pandemic.

Characteristics and outcomes of cryptococcosis among patients with COVID-19 compared to non-COVID-19 controls

Background. It remains unclear if there is an association between COVID-19 and cryptococcosis. The purpose of this study was to compare demographic characteristics and outcomes of cryptococcosis between patients with COVID-19 to non-COVID-19 controls. Methods. Patients 18 years and older with cryptococcosis were identified from TriNetX, a global federated research network, and separated into two cohorts based on a diagnosis of COVID-19 within 3 months prior to the index diagnosis of cryptococcosis. The primary outcome was the percent mortality in each group. The secondary outcomes included the proportion of patients in each group who had underlying comorbidities, received immunosuppressive medications, or required hospitalization or ICU admission. Propensity score matching was performed to control for differences between groups based on demographics and comorbidities. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for outcomes, with p < 0.05 as the cut off for statistical significance. Results. A total of 6252 patients with cryptococcosis were included, of which 4.5% (n=283) had COVID-19 prior to diagnosis of cryptococcosis. Mortality was similar between patients with and without COVID-19 (13% vs 10%, p=0.075). Patients with cryptococcosis and previous COVID-19 were older (55.2 +/- 14.5 years vs 52 +/- 15.2 years, p=0.0005) and more likely to be non-Hispanic (73% vs 65%, p=0.0049). More patients with COVID-19 had a history of transplant (30% vs 13%, p < 0.0001), malignancy (37% vs 21%, p < 0.0001), and diabetes (35% vs 19%, p < 0.0001), but not HIV (29% vs 31%, p=0.5482). Prednisone and dexamethasone use were higher among patients with previous COVID-19 (32% vs 15%, p < 0.0001 and 17% vs 7%, p < 0.0001, respectively). Hospitalization rates were similar (54% vs 57%, p=0.278), but more patients with COVID-19 required ICU admission (19% vs 11%, p < 0.0001). In propensity score-matched analysis, patients with COVID-19 remained at higher odds of ICU admission (OR 1.85, 95% CI 1.15-2.97, p=0.010), but lower odds of hospitalization (OR 0.57, 95% CI 0.41-0.81, p=0.001). Conclusion. Patients with COVID-19 who developed cryptococcosis had higher rates of comorbidities, corticosteroid use, and ICU admission but did not experience higher mortality compared to non-COVID-19 controls.

ISHAM 2022 Congress Abstracts

The proceedings contain 542 papers. The topics discussed include: risk factors associated with oropharyngeal candidiasis in COVID-19 patients: a case control study;diagnosis of fungal infections in animals: combining the old and the new to maximize results;genetics andgenomics of Malassezia species;diversity and hybridization in Malassezia furfur;the human pathobiont Malassezia furfur secreted protease MFSAP1 regulates cell dispersal and exacerbates skin inflammation;challenges in diagnosing and management of invasive fungal infections during the pandemic;Cryptococcus QPCR assays: the future for routine mycology labs and clinical trials dealing with cryptococcosis;epidemiology of myotic keratitis in developing countries;proteomics in fungal keratitis research: a road map to personalized treatment;incidence of mixed fungal infections in post-COVID-19 outbreak of mucormycosis;talaromycosis in HIV-negative patients: challenges and counter-measures;and evaluation of new tools for the diagnosis of histoplasmosis.

Preparing for Transplant - Screening and Prophylaxis of Donor and Recipients before Solid Organ Transplantation: Expert Group Opinion from South Asia

Infections are major cause of morbidity and mortality after transplantation. Although many infections are common worldwide, there are differences in various geographic locations. South Asia and India, in particular, has a very active transplant program for kidney and liver transplantation, however, there are no guidelines as how to screen and provide prophylaxis to solid organ transplant (SOT) recipients and donors for both specific infections prevalent in this region along with usual infections. Keeping this in mind, a working group was created comprising transplant physicians, surgeons, and infectious disease specialists from South Asia as well as experts from other countries. This working group developed guidelines based on published evidence, unpublished data from large centers in this region, along with expert opinion. This section of the guidelines deals with pretransplant screening of donors and recipients, which should be useful in dealing with transplants performed in this region for patients belonging to these countries, for those coming for transplantation from other countries, and for programs outside of South Asia who are screening donors and recipients from this region or who have spent significant time in this region. Copyright © 2022 Indian Journal of Transplantation Published by Wolters Kluwer - Medknow.

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician's high suspicion, early diagnosis, and prompt treatment.

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

Testing for Cryptococcosis at a Major Commercial Laboratory-United States, 2019-2021.

Background: Cryptococcosis is a serious opportunistic fungal disease, and the proportion of cases among patients with immunosuppressive conditions other than HIV or organ transplant has increased. Understanding laboratory testing patterns for cryptococcosis is useful for estimating its true burden and developing testing guidance. Methods: We identified cryptococcosis tests (cryptococcal antigen [CrAg], cryptococcal antibody, and fungal cultures) performed at a major national commercial laboratory ordered during March 1, 2019-October 1, 2021, and analyzed test results, patient and provider features, reasons for testing, geography, and temporal trends. Results: Among 29 180 serum CrAg tests, 4422 (15.2%) were positive, and among 10 724 cerebrospinal fluid (CSF) CrAg tests, 492 (4.6%) were positive. Frequent reasons for serum CrAg testing in nonhospital settings (10 882 tests) were HIV (44.6%) and cryptococcosis (17.0%); other underlying conditions were uncommonly listed (<10% total). Serum CrAg positivity declined from 25.6% in October 2019 to 11.3% in September 2021. The South had the highest positivity for serum CrAg tests (16.6%), CSF CrAg tests (4.7%), and fungal cultures (0.15%). Among 5009 cryptococcal antibody tests, 5 (0.1%) were positive. Conclusions: Few outpatient serum CrAg tests were performed for patients with immunocompromising conditions other than HIV, suggesting potential missed opportunities for early detection. Given the high positive predictive value of CrAg testing, research is needed to improve early diagnosis, particularly in patients without HIV. Conversely, the low yield of antibody testing suggests that it may be of low value. The decline in CrAg positivity during the COVID-19 pandemic warrants further investigation.

A Case of Pulmonary Cryptococcosis After Severe COVID-19 Pneumonia T. Roesch

Introduction / Case Presentation:46yo female with a history of CKD, atrial flutter, bioprosthetic valve with mitral ring, and recent COVID-19 pneumonia who presented to the emergency department (ED) with shortness of breath, fevers, and fatigue. Three months prior, she had been diagnosed with severe COVID-19 pneumonia, for which she received dexamethasone, remdesivir, tocilizumab, anakinra, and IVIG. She was discharged to a nursing facility with a prolonged steroid taper, ending 1 month prior to admission.In the ED, the patient had a chest x-ray that demonstrated bibasilar atelectasis and opacification, and a CT chest revealed right lower lobe consolidation and surrounding ground glass opacities. A respiratory pathogen PCR swab was negative. Sputum culture was negative for bacterial and fungal growth. Blood cultures did not grow any organisms. Given recent immunosuppression and imaging findings, a serum Cryptococcal antigen was drawn, which was positive with a titer of 1:128. A transthoracic needle biopsy of the patient's right lower lung was then performed. The specimen did not grow any bacteria or fungi and AFB stain on the tissue was negative. Pathology demonstrated a collection of histiocytes, neutrophils, and necrotic debris. PAS, GMS, and mucicarmine stains were positive for fungal organisms consistent with Cryptococcus species. Discussion: Cryptococcosis is a fungal infection due predominately to one of two encapsulated yeasts, Cryptococcus neoformans or Cryptococcus gattii. C. neoformans is found in soil worldwide, and infection typically begins with spore inhalation. Clinically significant disease is seen mostly in immunocompromised patients.Corticosteroids and interleukin inhibitors, such as anakinra (IL-1) and tocilizumab (IL-6), are used in the treatment of COVID-19. These medications have been associated with increased risk for opportunistic infections, including invasive fungal infections. The diagnosis of pulmonary cryptococcosis may be challenging, as symptoms are often nonspecific and may radiographically resemble bacterial pneumonia, malignancy, or other infections. Serum cryptococcal antigen detection tests may be helpful in establishing the diagnosis, as well as histopathology showing narrow-based budding yeast. Conclusion: Patients with prior COVID-19 infection commonly return to healthcare settings with sequelae of their previous coronavirus infection. In our case, it was the prior treatment of COVID-19, which included immunomodulating therapy, that lead to a secondary pulmonary cryptococcal infection. When evaluating pulmonary processes that evolve after an acute infection with COVID-19, it is important to keep a broad differential, including uncommon and/or opportunistic infectious etiologies, particularly when a patient has received prolonged courses of steroids and tocilizumab.

A case of fungal pneumonia in immunocompetent patient in nonendemic area

Introduction: Cryptococcal pneumonia is predominantly seen in immunosuppressed individuals and rarely in immunocompetent population. We report a case of middle age male with Cryptococcal pneumonia. History: A 45-year-old male farmer by occupation presented with shortness of breath for 2months, cough with sputum for 2 months associated with streaky hemoptysis, fever on and off for 1month, loss of appetite for 1 month, no history of SARS CoV 2, no h/o long term steroid usage and immunosuppression (HIV, malignancy) no significant family history. Presentation: Spo2- 98%RA, Blood pressure and pulse rate were normal. Examination reveaed Decreased breath sounds in left infra scapular area. Rest systemic examination was normal. Diagnosis: HIV, HBsAg were negative, Sputum Gram stain, KOH mount, culture was negative, Sputum CBNAAT was negative. Chest x-ray s/o non homogenous opacity in left mid zone. CT chest s/o Consolidation in superior segment of left lower lobe. Patient underwent FOB in view of hemoptysis. Bronchial washings cytology was negative, CBNAAT was negative, Fungal culture s/o Cryptococcus neoformans sensitive to amphotericin B and Flucytosine. Management: Microbiology based treatment with Amphotericin B and fluconazole. Clinical Implications: Any evidence of a cavitating nodule on CT in a patient presenting with cough & sob, a fungal infection is suspected irrespective of immune status and endemicity.

Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics.

Purpose of Review: Cryptococcosis of the central nervous system due to Cryptococcus gattii species complex is a serious mycosis with worldwide distribution but of great importance in the tropics. This article aims to review the progress made in these regions in the knowledge of this disease and its etiological agent. Recent Findings: They can be summarized in the presence in apparently immunocompetent patients of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a hidden risk factor for acquiring C. gattii infection; this finding strengthens the concept that C. gattii is an opportunistic pathogen. A greater knowledge of the clinical and molecular epidemiology of C. gattii infection and of the different environmental niches of this fungus in the tropics. The discovery of a new lineage of C. gattii, VGV, in environmental samples from Africa. Until now, the COVID-19 pandemic has not meant an increase in cryptococcosis cases. Summary: Advances have been made in the identification of risk factors for cryptococcosis due to C. gattii as well as in the knowledge of its etiological agent and its relationship with the environment. Remarkably, there have been no significant achievements in diagnosis and treatment notwithstanding the documented importance.