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Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.
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Objectives: In COVID-19 associated acute respiratory distress syndrome (ARDS) requiring VV-ECMO, ventilator-associated-pneumonia (VAP), pulmonary aspergillosis and viral reactivations are observed frequently, but there is only little knowledge on incidence, onset and causative pathogens. This study analyzes frequency of VAP, pulmonary aspergillus infections, and viral reactivations in a large cohort of patients with ARDS treated with VV-ECMO due to either COVID-19 or Influenza. Method(s): Retrospective analysis of all consecutively patients at the University Hospital Regensburg requiring VVECMO due to COVID-19 (March 2020 and May 2022) or Influenza (May 2012 and December 2022). VAP was diagnosed according to current guidelines. Pulmonary Aspergillosis met criteria of probable COVID-associated Aspergillosis according to current guidelines. Result(s): 147 patients (age (median [IQR]) 55.3 [48.7 - 61.7], SOFA at VV-ECMO initiation 9 [8 - 12], 23 [14 - 38] days on VV-ECMO) suffering from COVID-19 and 72 influenza patients (age 55.3 [46 - 61.3], SOFA at VV-ECMO initiation 13 [10 - 15], 16 [10 - 23] days on VV-ECMO) were included in the analysis. Pulmonary superinfections were more frequent in COVID-19 than in influenza (VAP: 61% vs. 39%, pulmonary Aspergillosis: 33% vs. 22%, CMV reactivation: 19% vs. 4%, HSV reactivation: 49% vs. 26%.) The first episode of VAP in COVID-19 and Influenza was detected 2 days [1 - 15] after and 1 day (-3 - 22) before ECMO initiation, respectively. First VAP-episode in COVID-19 were mainly caused by Klebsiella spp. (29%,), Staphylococcus aureus (27%) and E. coli (11%). Further VAP-episodes (30% in COVID-19) and relapses of VAP were mainly caused by Klebsiella spp. (53%, 64%, respectively). In Influenza, VAP was mainly caused by Staphylococcus aureus (28%) and Streptococcus pneumoniae(28%), further VAP episodes were not observed. Conclusion(s): Superinfections were common in patients treated with VV-ECMO and occur more frequently in COVID-19 ARDS compared to Influenza. VAP occurs early and may significantly contribute to the need of VV-ECMO. Therefore, a meticulous routine microbiologic workup is advisable. The observed differences in the spectrum of secondary infectious agents in COVID19 compared to Influenza are not understood yet.
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Intro: Invasive aspergillosis of CNS is a severe form of aspergillosis & is associated with high mortality. Most of these cases are suspected & diagnosed in neutropenic patients. We hereby describe a series of 15 patients with CNS aspergillosis in non-neutropenic patients from a tertiary care hospital in India. Method(s): All patients with clinical & radiological features suggestive of CNS aspergillosis were screened for microbiological evidence of invasive aspergillosis, either by demonstration of hyphae by microscopy or histology, culture or galactomannan assay. Patients demographic details, clinical features, risk factors, diagnosis, management & outcome details were documented. Finding(s): A total of 15 patients were found to have CNS aspergillosis, 5 isolated CNS infections & 10 showing concomitant CNS & pulmonary aspergillosis in one between January 2021 to July 2022. The average age was 41.46+/-14.6y, with majority being male. Among the risk factors, most common ones were fungal sinusitis (46.6%), steroid use (40%), COVID-19 (33.3%). One patient had history of endoscopic sinus repair, another had h/o lung abscess. Most common symptoms of CNS aspergillosis were headache (73.3%), fever (60%), altered sensorium (53.3%) & seizures (47.6%). Radiologically, the common findings included ring enhancing lesion, s/o cerebral abscesses were observed in four patients. Direct microscopy s/o fungal hyphae were reported in 5 patients, with 4 culture positives. Average serum galactomannan was 1, while CSF galactomannan showed better sensitivity with mean CSF galactomannan being 2.53. Almost all patients were treated with Voriconazole based on weight, but showed high mortality of 60% even after initiation of therapy. Complete resolution were seen in only two patients, while 4 patients remaining static in improvement during 6 months follow up. Conclusion(s): Invasive CNS aspergillosis must be suspected even with nonneutropenic patients with newer emerging risk factors like steroid use, COVID-19 & h/o fungal sinusitis presenting with clinical & radiological manifestations.Copyright © 2023
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Pulmonary aspergillosis (PA) is a category of respiratory illnesses that significantly impacts the lives of immunocompromised individuals. However, new classifications of secondary infections like influenza associated aspergillosis (IAA) and COVID-19 associated pulmonary aspergillosis (CAPA) only exacerbate matters by expanding the demographic beyond the immunocompromised. Meanwhile anti-fungal resistant strains of Aspergillus are causing current treatments to act less effectively. Symptoms can range from mild (difficulty breathing, and expectoration of blood) to severe (multi organ failure, and neurological disease). Millions are affected yearly, and mortality rates range from 20-90% making it imperative to develop novel medicines to curtail this evolving group of diseases. Chalcones and imidazoles are current antifungal pharmacophores used to treat PA. Chalcones are a group of plant-derived flavonoids that have a variety of pharmacological effects, such as, antibacterial, anticancer, antimicrobial, and anti-inflammatory activities. Imidazoles are another class of drug that possess antibacterial, antiprotozoal, and anthelmintic activities. The increase in antifungal resistant Aspergillus and Candida species make it imperative for us to synthesize novel pharmacophores for therapeutic use. Our objective was to synthesize a chalcone and imidazole into a single pharmacophore and to evaluate its effectiveness against three different fungi from the Aspergillus or Candida species. The chalcones were synthesized via the Claisen-Schmidt aldol condensation of 4-(1H-Imizadol-1-yl) benzaldehyde with various substituted acetophenones using aqueous sodium hydroxide in methanol. The anti-fungal activity of the synthesized chalcones were evaluated via a welldiffusion assay against Aspergillus fumigatus, Aspergillus niger, and Candida albicans. The data obtained suggests that chalcone derivatives with electron-withdrawing substituents are moderately effective against Aspergillus and has the potential for further optimization as a treatment for pulmonary aspergillosis. This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medicine Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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The novel coronavirus (COVID-19) pandemic announced by the World Health Organization in March 2020 assigned medical community to the new tasks that require immediate solutions. Recent studies have shown that invasive aspergillosis associated with COVID-19 often complicates a course of the disease and leads to death. This review aims to describe the diagnosis and therapy challenges due to COVID-19 associated invasive pulmonary aspergillosis.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Aim of this study is to evaluate the incidence of fungal infections in COVID-19 intensive care unit (ICU) patients, to identify potential risk factors and to investigate whether differences in patients' outcomes are depicted. Material-Methods: This prospective observational study included critically ill patients diagnosed with COVID-19 that were admitted from 1/9/2020 to 1/11/2021 in ICU of the 1st Respiratory Department of Sotiria Chest Diseases Hospital. Epidemiologic characteristics, severity of disease, medication, outcome and complications were recorded. Result(s): Out of 300 patients included (213 men, 60,4+/-13,23 (mean+/-SD) years-old), 22 (7,3%) developed fungal infections (16 COVID-19 Associated Pulmonary Aspergillosis, 5 COVID-19 Associated Candidemia and 1 both). They were 6 female & 16 male, 55,73+/-13,28 years-old. Most patients had co-infections with multi-drug resistant bacteria. Patients with fungal infections were statistifically more on high dose of corticosteroids, invasive mechanical ventilation and renal replacement treatment (p<0.05). They had statistically more positive blood and bronchial secretion cultures, as well as more incidents of septic shock, venous thromboembolism and varotrauma (p<0.05). Their PaO2/FiO2 ratio on admission was statistically lower (p<0.05). Finally, after adjustment for confounfing factors and ICU days, they were at higher risk of dying (50% mortality). Conclusion(s): Fungal infections are a significant co-infection in critically ill COVID-19 patients. Those patients seem to have more severe respiratory failure on admission, be on higher doses of corticosteroids and in need of organ failure support. They also seem to develop more complications of COVID-19 and be at a higher risk of dying.
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The article provided the information about the results of clinical-morphological analysis of the practical observation with pulmonary aspergillosis associated with COVID-19 and undiagnosed when the patient was alive. The pulmonary aspergillosis associated with COVID-19 is one of the widespread complications. However, in numerous cases, the pulmonary aspergillosis associated with COVID-19 is not diagnosed due to its unclear signs and lack of information about it. An infiltrate with signs of destruction was noted during X-ray examination of the lower part of the right lung of the observed patient. It was evaluated as destructive pneumonia associated with bacterial infection. However, despite the patient had type II diabetes, no additional examination methods were applied to exclude aspergillosis. Disruption of the protective properties of the bronchial epithelium and the effect of oseltamivir type drugs may also contribute to the entry of aspergillus fungi into the lung tissue. According to the authors, during the development of diagnosis, treatment and prevention strategy of COVID-19in the patients with pulmonary aspergillosis it is important to study the interaction of these diseases.Copyright © 2022 Authors. All rights reserved.
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Background: COVID-19 associated pulmonary aspergillosis (CAPA) complicates the course of critically ill COVID-19 patients. Delay in diagnosis and reports of azole resistance in CAPA patients lead to adverse outcome. We had previously reported CAPA rates of 21.7% from our center with high mortality. To detect azole resistance in Aspergillus species isolated from CAPA patients, we performed azole resistance screening. Material(s) and Method(s): Aspergillus species isolated from tracheal aspirates of CAPA patients admitted in Aga Khan University Hospital, Karachi, Pakistan during July 2020- January 2022, were screened for azole resistance as per CDC protocol. Minimum inhibitory concentration of screening positive strains were determined using YeastOne Sensititre plate. Result(s): 92 Aspergillus isolates were screened from 73 CAPA patients for azole resistance. Only 2 (2.17%) A. flavus isolates showed growth on voriconazole well, while other 90 (97%) isolates were screened negative for resistance (Table. 1). MICs of these two strains against posaconazole, voriconazole and itraconazole were 0.5 ug/mL, 1 ug/mL and 0.25ug/mL respectively. Table. 1: Aspergillus species distribution and growth on azole resistance screen agar Conclusion(s): We also did not find any azole resistance in this study. Periodic surveillance for the emergence of azole-resistant clinical isolates using molecular approaches is essential.
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Background: Early identification of COVID-19-associated pulmonary aspergillosis (CAPA) is particularly challenging in low- middle-income countries where diagnostic capabilities are limited, and risk factors for CAPA have not been identified. It is also essential to recognise CAPA patients who are likely to have a poorer outcome to decide on aggressive management approaches. Therefore, this study aimed to identify risk factors and outcomes for CAPA among admitted moderate to critical COVID-19 patients at our centre in Pakistan. Methods: An unmatched case–control study with ratio of 1:2 was conducted on hospitalised adult patients with COVID-19 from March 2020–July 2021. Cases were defined according to European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Controls were defined as patients hospitalised with moderate, severe or critical COVID-19 without CAPA. Results: A total of 100 CAPA cases (27 probable CAPA;73 possible CAPA) were compared with 237 controls. Critical disease at presentation (aOR 5.04;95% CI 2.18–11.63), age ≥ 60 years (aOR 2.00;95% CI 1.20–3.35) and underlying co-morbid of chronic kidney disease (CKD) (aOR 3.78;95% CI 1.57–9.08) were identified as risk factors for CAPA. Patients with CAPA had a significantly greater proportion of complications and longer length of hospital stay (p-value <.001). Mortality was higher in patients with CAPA (48%) as compared to those without CAPA (13.5%) [OR = 6.36(95% CI 3.6–11)]. Conclusions: CAPA was significantly associated with advanced age, CKD and critical illness at presentation, along with a greater frequency of complications and higher mortality. © 2022 Wiley-VCH GmbH.
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Background. Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-beta-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19. Methods. We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality. Results. Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients' serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13). Conclusion. In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19.
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Background. Severe COVID-19 elicits a hyperimmune response frequently amenable by high-dose steroids, although treatment may increase the risk for opportunistic infections. Invasive pulmonary aspergillosis (IPA) is a known complication of COVID-19, termed COVID-19 associated pulmonary aspergillosis (CAPA).While steroid use is a known risk factor for CAPA, the role of cumulative steroid dose in the development of CAPA is unclear. This study evaluates the relationship between cumulative steroid dose in hospitalized individuals and the risk for CAPA. Methods. This retrospective cohort study includes 130 hospitalized patients with RT-PCR-confirmed COVID-19 pneumonia at a specialized center in north Mexico. Patients who developed CAPA were matched by age and gender to two patients who did not develop CAPA. CAPA was defined according to 2020 ECMM/ISHAM criteria. Patients with either possible, probable, or proven CAPA were considered positive cases. Steroid dose was converted to dexamethasone equivalents according to potency and duration. Cumulative dose was obtained in every patient from admission until discharge or diagnosis of CAPA. We assessed the risk of CAPA by the continuous cumulative steroid dose using a logistic regression model. Results. A total of 42 patients were diagnosed with possible, probable, or confirmed CAPA and were matched to 88 controls. Mean age was 61 +/- 14 years, 94 (72%) were male, 11 (12%) were smokers, and 55 (50%) were obese. Mean cumulative steroid dose was 66 +/- 75 in patients without CAPA vs 195 +/- 226 in patients with CAPA (P< 0.001) (Figure Panel A). The risk for CAPA was higher as the cumulative dose of steroids increased, in a near-linear relationship (OR 1.008;95% CI 1.003, 1.013, P< 0.001) (Figure Panel B). Conclusion. Patients who develop CAPA have a history of higher cumulative steroid dose during hospitalization. The risk for CAPA increases in a near-linear fashion as the cumulative steroid dose during hospitalization increases. While causality cannot be drawn by this study, caution while prescribing high-dose steroids is warranted among individuals hospitalized with COVID-19 pneumonia. Clinical suspicion of CAPA should increase in individuals with a high cumulative dose of steroids and clinical decline.
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Purpose: Invasive fungal infection (IFI) complicating Coronavirus disease of 2019 (COVID-19) has been increasingly recognized. IFI is a common opportunistic infection in solid organ transplant (SOT), but association with COVID-19 is unknown. Method(s): This was a retrospective study of all SOT recipients hospitalized with COVID-19 between March 2020 and Oct 2021. IFI was defined based on EORTC/ MSG criteria. Result(s): 107 SOT recipients were hospitalized due to COVID-19. 17 patients were excluded because they were on a systemic antifungal agent on admission. Median age was 62 yrs. 46% were female. 59% (53) were recipients of kidney, 17% (15) of lung, 11% (10) each of heart and liver, and 2% (10) of small bowel. 8% (7) of patients developed IFI within 90 days of COVID-19 (2 proven and 5 probable) (Table): 3 due to yeasts (2 bloodstream and 1 lung), and 4 pulmonary aspergillosis. Median time from COVID-19 diagnosis to IFI was 22 days (1d to 78d). Mechanical ventilation (P = 0.01) and augmented immunosuppression (p = 0.04) were risk factors for IFI;receipt of dexamethasone or IL-6 inhibitor were not risk factors. IFI associated with more prolonged hospital stay (median of 23 days (7-120d) vs 10d (1-80d), respectively). The 90-day mortality after COVID-19 diagnosis was 23% (21), higher for patients with IFI (57% vs 20%;p=0.04). By univariate analysis, the risk factors for death were: use of dexamethasone (p=0.011), IL-6 inhibitor (p=0.001), and IFI (p=0.049);SARS-CoV-2 monoclonal antibody (Mab) was protective (p=0.06). By multivariate analysis, receipt of IL-6 inhibitor (p=0.001) and IFI (p=0.009) were independent risk factors for death;Mab was protective (p=0.02). Overall, 18% (16) patients received systemic antifungals (AF);11% (9) received AFs without any IFI diagnosis and they all received anti-mold agents. Conclusion(s): The incidence of IFI complicating COVID-19 was 8%, and IFI was associated with a higher mortality. The association between receipt of IL-6 inhibitor and death among SOT patients is of concern. Risk and benefit of this agent along with it's side effect should be carefully evaluated in larger trials of SOT and other immunosuppressed COVID-19 patients. (Table Presented).
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SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: COVID-19 Associated Pulmonary Aspergillosis (CAPA) is a subset of invasive pulmonary aspergillosis occurring in patients actively infected with or recovering from COVID-19. It has mostly been described in immunocompromised or severely ill patients requiring invasive mechanical ventilation[1-6]. The authors report a case of CAPA infection in an ambulatory and immunocompetent patient with prior lung resection. CASE PRESENTATION: A 20-year-old male presented to a Comprehensive Cancer Center for fever and hemoptysis. He carried a diagnosis of metastatic germ cell tumor to his lungs, status post left upper-lobe wedge resection. He had completed bleomycin, etoposide, and cisplatin (BEP) chemotherapy one year earlier. He was recently diagnosed with COVID-19 one month prior to admission and treated as an outpatient with monoclonal antibodies. He reported ongoing cough productive of clear sputum since his diagnosis, which had worsened over the previous two days and was now blood-tinged. He had been afebrile for weeks before noting new fevers over the same period. Physical examination was notable for fever to 38.6°C and lungs clear to auscultation. His labs were significant for a WBC of 14.5 K/mcl (82.5% neutrophils), Cr 2.1 mg/dL (baseline 1.5 mg/dL), and normal platelets and coagulation studies. Serum Aspergillus galactomannan was normal. Repeat SARS-CoV-2 PCR was negative. Chest x-ray was unchanged. V/Q scan showed no evidence of pulmonary embolism. Non-contrast CT chest performed on hospital day #4 revealed a partial opacification and increased wall thickness of patient's largest left upper lobe surgical cavitation (see Image 1). A bronchoscopy was performed day #6, with bronchoalveolar lavage (BAL) galactomannan >5.56 (normal <0.5)7;fungal culture was significant for septate hyphae. He was started on voriconazole with improvement in his symptoms and discharged day #9. DISCUSSION: Immunocompromised patients with prolonged neutropenia, solid-organ or stem cell transplants, and patients with advanced AIDS are at highest risk of contracting PA[8-9]. ARDS secondary to viral pneumonia is also a common precipitant in immunocompetent patients[1-6,10,11]. The exact mechanism of this association remains unknown, but it is postulated to occur due to multiple factors, including host immune dysregulation[1,2], widespread exposure to corticosteroids[1,2], concomitant lung disease[1], and viral-induced lymphopenia[2]. We report a case of an immunocompetent patient with prior lung resection recovering from COVID-19 who experienced a secondary worsening of symptoms ultimately found to have CAPA to further highlight the link between these conditions. CONCLUSIONS: While many of CAPA case reports describe patients with typical risk profiles for CAPA, this case suggests that clinicians should consider structural lung disease alone in an otherwise immunocompetent, ambulatory individual to be a potential risk factor. Reference #1: See Image 2 for full list of references. DISCLOSURES: No relevant relationships by Raphael Rabinowitz No relevant relationships by Matthew Velez
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SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Since the start of the COVID-19 pandemic, COVID-19 Associated Pulmonary Aspergillosis (CAPA) has been on the rise. This superinfection, if not properly identified and treated, has shown to increase mortality up to 67% in COVID-19 patients. We are presenting a late presentation of CAPA after 4-month of COVID-19 infection and treated successfully. CASE PRESENTATION: A 57-year-old female patient with past medical history type 2 diabetes mellitus, hypertension and cardiomyopathy in addition to COVID-19 pneumonia treated for months ago with azithromycin, Bamlanivimab/Etesevimab, and Dexamethasone who presents to the hospital with massive hemoptysis and shortness of breath requiring intubation and mechanical ventilation. There was no reported history of recent travel, smoking, alcohol, or illicit drug use. Physical exam showed diminished lung sounds at the right lower lobe. Her labs showed mild leukocytosis, lactic acidosis and negative COVID-19 PCR. CT scan showed dense consolidation on right lower lobe consistent with lobar pneumonia and centrilobular ground glass opacities in the right upper lobe. Bronchoscopy showed complete obstruction of right bronchus intermedius and minimal blood clots in LLL. BAL respiratory culture, fungal smear, acid fast bacilli were non-diagnostic and negative for malignancy. Patient continued to have hemoptysis and bronchoscopy was repeated with negative cytology and cultures. The patient continued to have hemoptysis and she was transferred to tertiary center were bronchoscopy was repeated and confirmed right bronchus intermedius stenosis, blood clots, and suspicious right mainstem nodules with mucosal lesion. Biopsy results from bronchoscopy came back positive for the morphologic features of Aspergillus species. The patient was started on voriconazole with significant improvement in her symptoms. DISCUSSION: The recent literature of COVID-19 suggest association between COVID infection and invasive pulmonary Aspergillosis. COVID-19 virus causes damage in the airway epithelium and enable aspergillus to invade the pulmonary tract leading to serious infections with Aspergillus. It has also been known that Aspergillus infections are associated with diabetes mellitus and immune suppression which can be precipitated by steroid use and other treatments for COVID-19 infection like IL-6 inhibitors. Here in our patient with help of tissue biopsy we diagnosed CAPA, started treatment early and treated successfully. CONCLUSIONS: CAPA can be difficult to diagnose and needs high index of suspicion in the appropriate clinical scenario when dealing with post COVID respiratory complaints like hemoptysis. Bronchoalveolar lavage alone without tissue biopsy might miss the diagnosis in the context of invasive aspergillosis like the scenario we observed in our case. Doing tissue biopsy through bronchoscopy might add more clinical benefit when Aspergillus infections are suspected. Reference #1: Chih-Cheng Lai, Weng-Liang Yu, COVID-19 associated with pulmonary aspergillosis: A literature review, https://doi.org/10.1016/j.jmii.2020.09.004 DISCLOSURES: No relevant relationships by Haytham Adada No relevant relationships by Mahmoud Amarna No relevant relationships by Rishika Bajaj No relevant relationships by Camelia Chirculescu No relevant relationships by Sonia Dogra No relevant relationships by Azad Patel
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 patients requiring admission to an ICU have a higher risk of invasive pulmonary aspergillosis (IPA) with a reported incidence of 19.6%-33.3%. CASE PRESENTATION: A 63-year-old male presented with progressively worsening dyspnea for one week. He has a past medical history of atrial fibrillation, hypertension, and obesity. He was tested positive for COVID about two weeks prior. He did receive a single dose of Moderna vaccine. Initial chest x-ray(CXR) showed diffuse ground-glass opacities. He was initiated on Remdesivir and decadron, and later received a dose of tocilizumab. He was intubated on hospital day 3 for worsened hypoxemia. Repeat CXR suggested some improvement but a new left lower lobe airspace haziness. He also had new-onset leukocytosis with elevated procalcitonin level. He was started on cefepime for concern of superimposed hospital-acquired pneumonia. A second dose of tocilizumab was administered. No clinical improvement was seen, and additional workups were obtained. Serial CXRs revealed increasing diffuse airspace opacities concerning for ARDS. Tracheal aspirate culture grew coagulase-negative staphylococcus and Aspergillosis Fumigatus. Cefepime was changed to vancomycin, and voriconazole and caspofungin were added. Unfortunately, the patient's respiratory status worsened with increasing ventilation requirement. He also developed septic shock and acute renal failure requiring CVVH. He became even more hypotensive after CVVH initiation, and multiple vasopressors were required to maintain his hemodynamics. Unfortunately, he continued to deteriorate and he also developed profound respiratory acidosis. He died shortly afterwards after family decided to withdraw care. DISCUSSION: In this case, in addition to superimposed bacterial pneumonia, pulmonary aspergillosis likely also contributed to his clinical deterioration. The mechanism by which fungal infections develop in COVID-19 infection is not well-understood. Severe COVID-related immune dysregulation, ARDS, and high-dose steroids use are potential culprits for the increased risk of IPA. Tocilizumab, an IL-6 receptor monoclonal antibody used in patients with severe COVID-19 infection, may also predispose the patient to IPA according to post-marketing data. The mortality rate from current case reports is as high as 64.7%. Diagnosis and treatment in such a scenario remain a challenge. Sputum culture, serum Beta-galactomannan, Beta-D glucan, and aspergillosis PCR have low sensitivity. Tissue biopsy and CT scan in critically ill patients are often not feasible. Voriconazole is usually considered the first-line treatment in IPA. CYP3A4-mediated drug interactions between azoles and antiviral agents require further investigation. CONCLUSIONS: Clinicians should be aware that severe COVID-19 patients are at higher risk of IPA. The prognosis is poor. Early detection and treatment in clinically deteriorated patients are warranted. Reference #1: Borman, A.M., Palmer, M.D., Fraser, M., Patterson, Z., Mann, C., Oliver, D., Linton, C.J., Gough, M., Brown, P., Dzietczyk, A. and Hedley, M., 2020. COVID-19-associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory. Journal of clinical microbiology, 59(1), pp.e02136-20. Reference #2: Lai CC, Yu WL. COVID-19 associated with pulmonary aspergillosis: A literature review. J Microbiol Immunol Infect. 2021;54(1):46-53. doi:10.1016/j.jmii.2020.09.004 Reference #3: Thompson Iii GR, Cornely OA, Pappas PG, et al. Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19. Open Forum Infect Dis. 2020;7(7):ofaa242. Published 2020 Jun 19. doi:10.1093/ofid/ofaa242 DISCLOSURES: No relevant relationships by Jason Chang No relevant relationships by Jason Chang No relevant relationships by kaiqing Lin No relevant relationships by Guangchen Zou
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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
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SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Pulmonary aspergillosis is a recognized complication of COVID-19. Options for diagnostic evaluation in patients with suspected pulmonary aspergillosis include serum galactomannan, beta-D-glucan, Aspergillus PCR, fungal cultures and tissue biopsy. Diagnosis is challenging due to the risks and logistical barriers associated with procedural/surgical tissue biopsy and the variable reliability of serum biomarkers. We present a case of a 76-year-old male who developed invasive pulmonary aspergillosis after a COVID-19 respiratory infection. CASE PRESENTATION: 76-year-old male with a past medical history that includes emphysematous COPD, history of chronic lymphocytic leukemia in remission, on ibrutinib, who contracted SARS-CoV-2 resulting in hypoxemic respiratory failure and requiring hospital admission and was treated with dexamethasone and remdesivir. He was discharged home and due to his worsening respiratory condition, he was readmitted to the hospital next month. Ct chest performed revealed pulmonary embolism and diffuse multifocal opacification with interspersed scattered dense opacities and nodules with cavitary lesions in the right upper lobe. A bronchoscopy was performed and the Aspergillus antibody test, beta D glucan and galactomannan antigens resulted as negative. Due to this, voriconzaole was discontinued. Subsequently CT-guided lung biopsy demonstrated Aspergillus. Eventually, fungal cultures from BAL began growing fungus. DISCUSSION: Our patient initially presented with a Covid infection in January 2022 he was initially treated with remdesivir, 14 days of baricitinib and 10 days of Decadron followed by a steroid taper (due to his underlying COPD). He did not receive tocilizumab. He was found to have progression of the cavitary lesions during a third admission. We suspect that the main contributing factors for the development of invasive pulmonary aspergillosis are related to interleukin production, distorted architecture from COVID-19 infection and multiple courses of steroids. This case report demonstrates the importance of having a high clinical suspicion for invasive pulmonary aspergillosis in all patients with COVID-19 infection. It also demonstrates that serum biomarkers are not reliable indicators of infection and cannot be used to definitively rule out infection or to exclude treatment with antifungal therapy. It should be noted that positive serum biomarkers in patients with true invasive aspergillosis have a higher mortality rate as compared to those without positive serum biomarkers. This case also underscores the importance of obtaining tissue diagnosis in patients where there is a high suspicion for fungal infection when all other studies are equivocal. CONCLUSIONS: We believe that this case underscores the importance of maintaining a high clinical suspicion for opportunistic and fungal infections in patients with COVID-19, regardless of the serum biomarkers. Reference #1: Arastehfar A, Carvalho A, van de Veerdonk FL, et al. Covid-19 associated Pulmonary Aspergillosis (capa)—from immunology to treatment. Journal of Fungi. 2020;6(2):91. doi:10.3390/jof6020091 Reference #2: Machado M, Valerio M, Álvarez-Uría A, et al. Invasive Pulmonary Aspergillosis in the COVID-19 ERA: An expected new entity. Mycoses. 2020;64(2):132-143. doi:10.1111/myc.13213 Reference #3: Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis. Drugs. 2007;67(11):1567-1601. doi:10.2165/00003495-200767110-00004 DISCLOSURES: No relevant relationships by Hira Bakhtiar No relevant relationships by Amanda Lindo No relevant relationships by Carlos Merino No relevant relationships by Joanna Moore
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since the start of Covid-19 pandemic, several respiratory microorganisms have been identified that cause coinfection with Sars-Cov-2. Bacteria like Staphylococcus aureus and viruses like influenza are some of the identified pathogens. Rarely, fungal infections from Aspergillus are also being reported. CASE PRESENTATION: 59-year-old male with past medical history of hypertension and hyperlipidemia was admitted for shortness of breath and was found to be positive for Covid-19. He received Remdesivir, dexamethasone & tocilizumab. He required non-invasive ventilation via continuous positive airway pressure but continued to remain hypoxemic with elevated procalcitonin, he was treated with cefepime for bacterial pneumonia. Patient required emergent intubation and eventually underwent tracheostomy. He developed methicillin-resistant Staphylococcus aureus pneumonia for which he received vancomycin. He was eventually discharged to long term acute care facility. Patient was readmitted after 2 months due to worsening respiratory status. Computed Tomography Angiography of chest was negative for pulmonary embolism but showed pleural effusion. He underwent thoracentesis which showed exudative effusion with negative cultures. Echocardiogram showed right heart failure. Patient's symptoms were believed to be due to Covid-19 fibrosis. He required home oxygen and also received pulmonary rehabilitation. One year after the initial Covid-19 infection, he developed pulmonary hypertension and was referred for lung transplant consultation. However, he developed severe hemoptysis requiring intubation and vasopressors. Galactomannan was positive, Karius digital culture revealed Aspergillus Niger for which he received voriconazole. He was not deemed a suitable candidate for lobectomy. Patient developed arrhythmia and had prolonged QT interval so voriconazole was switched to Isavuconazole. He continued to have hemoptysis and his condition did not improve so family requested to transition care and patient passed away. DISCUSSION: Several studies have proven co-infection of Aspergillus with Covid-19. This case highlights Aspergillus infection approximately 1 year after initial Covid-19 infection. Sars-Cov-2 causes damage to airway lining which can result in Aspergillus invading tissues. IL-6 is increased in severe Covid-19 infection. Tocilizumab is an anti-IL-6 receptor antibody that has been approved for treatment of Covid-19 pneumonia. However, IL-6 provides immunity against Aspergillus so use of tocilizumab decreases protection against Aspergillosis which is usually the reason for co-infection. However, in this case patient developed fungal infection later during Covid-19 fibrosis stage. CONCLUSIONS: Recognizing fungal etiology early on is important in Covid-19 patients as mortality is high and appropriate intervention can reduce morbidity and mortality. Some patient may eventually require lung resection. Reference #1: Kakamad FH, Mahmood SO, Rahim HM, Abdulla BA, Abdullah HO, Othman S, Mohammed SH, Kakamad SH, Mustafa SM, Salih AM. Post covid-19 invasive pulmonary Aspergillosis: a case report. International journal of surgery case reports. 2021 May 1;82:105865. Reference #2: Nasrullah A, Javed A, Malik K. Coronavirus Disease-Associated Pulmonary Aspergillosis: A Devastating Complication of COVID-19. Cureus. 2021 Jan 30;13(1). Reference #3: Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-associated pulmonary aspergillosis (CAPA). Journal of Intensive Medicine. 2021 Oct 25;1(02):71-80. DISCLOSURES: No relevant relationships by Maria Haider Baig
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SESSION TITLE: Infectious Complications with Obstructions and Connections SESSION TYPE: Case Reports PRESENTED ON: 10/17/2022 03:15 pm - 04:15 pm INTRODUCTION: Invasive pulmonary fungal infections are a challenge for diagnosis. One of the most common types is Invasive pulmonary aspergillosis. It occurs usually among immunocompromised patients [1], so an early diagnosis is warranted for potential better outcome. Evidence of calcium oxalate can be an early diagnostic tool for such an infection. The presence of calcium oxalate crystals can be detected within 24 hours under polarized light in the microbiology labs. We present this case to highlight the potential importance of pulmonary oxalosis in diagnosing pulmonary aspergillosis. CASE PRESENTATION: A 62-year-old-woman with limited breast cancer was admitted to the hospital seven days after her last cycle of docetaxel and cyclophosphamide with COVID-19 pneumonia and hypoxemic respiratory failure. She was not neutropenic. She received a full course of dexamethasone and remdesivir. Sputum cultures subsequently grew Klebsiella aerogenes for which she was treated with antibiotics but failed to significantly improve over four weeks. Repeat chest computed tomography (CT) showed progressive multifocal airspace opacities with new areas of cavitation. Patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. Transbronchial biopsy specimen from the right upper lobe showed bronchial mucosa and lung parenchyma with calcium oxalate crystals and no organisms. Biopsy specimen from the right middle lobe showed fungal organisms consistent with Aspergillus invading bronchial mucosa and lung parenchyma. Several days later, serum beta-D-glucan returned within normal limits, serum galactomannan was significantly elevated, and BAL culture grew Aspergillus niger. Patient improved with antifungal therapy. DISCUSSION: Fungal pneumonia has high morbidity and mortality. It is essential to start antifungal therapy as soon as possible. Pulmonary oxalosis or calcium oxalate has been seen among Aspergillus Fumigatus and Aspergillus Niger [2-3]. It is a combination of oxalic acid which is produced by Aspergillus spp. and calcium from blood supply of an invaded tissue. Further progression of lesions can be due to calcium oxalate toxicity itself [4-5]. In our case, clinical suspicion for pulmonary aspergillosis was high and we were able to document fungal invasion of lung parenchyma on one of the lung specimens. Though fungal culture is very sensitive and specific, it can take several days to result. Tissue staining for crystals can be performed quickly and provide more timely information when deciding about starting anti-fungal therapy. CONCLUSIONS: Pulmonary oxalosis, calcium oxalate deposition, can be seen in aspergillus infection and should be considered as an early diagnostic tool for invasive pulmonary aspergillosis. Reference #1: Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121): 156–174, doi: 10.1183/09059180.00001011 Reference #2: U. Pabuccuoglu, Aspects of oxalosis associated with aspergillosis in pathology specimens, Pathol. Res. Pract. 201 (2005) 363–368 Reference #3: Osholowu OS, Kak V, Singh H. Pulmonary oxalosis in pulmonary aspergillosis syndrome. Adv Respir Med. 2020;88(2):153-156. doi: 10.5603/ARM.2020.0090. PMID: 32383468. DISCLOSURES: No relevant relationships by Mohammed Alsaggaf No relevant relationships by Daniel Baram No relevant relationships by Ivana Milojevic
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SESSION TITLE: Global Pulmonary Cases SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: COVID 19 is associated with hyper- inflammation with levels of IL 6 correlating with the severity of COVID 19. IL6 causes increased vascular permeability and endothelial dysfunction and plays a major role in the development of ARDS.[1] Tocilizumab is a monoclonal antibody against the IL6 receptor which is being used for COVID pneumonia. Large randomized controlled trials including REMAP-CAP and RECOVERY reported a mortality benefit of tocilizumab in certain patients [3]. Aspergillus is a mold that causes variety of pulmonary infections depending on host's immune status. In immunocompromised hosts, it causes invasive pulmonary aspergillosis [2]. Symptoms initially are similar to bronchopneumonia: cough with sputum, dyspnea, fever not responsive to antibiotics. With disease progression, patients experience pleuritic chest pain and hemoptysis. CASE PRESENTATION: 69 y/o female came to ER with complaint of dyspnea and cough. PMH significant for Diabetes. She had a recent admission for COVID 3 weeks ago during which she received tocilizumab. This time, her vitals were HR- 96 RR- 24 Temp- 99.6 BP- 124/72, Sat- 88% on 2L NC. Labs WBC 31.1 D dimer- 2.17 ABG PO2- 61. CT pulmonary angiogram was consistent with left mid lung zone cavitary mass with an air-fluid level measuring 5 x 8 cm in transverse and AP dimension. Patient was started on broad-spectrum antibiotics (vancomycin, cefepime, metronidazole). Sputum cultures, Beta glucan assay, AFB and fungal immunodiffusion panel was ordered. Beta D Glucan assay came positive. Fungal immunodiffusion panel was negative. Bronchoscopy was done and AFB, aspergillus antigen and cultures were collected. BAL aspergillus antigen came positive and KOH fungal culture grew Aspergillus Fumigatus. Voriconazole was started. She was discharged on voriconazole for 12 weeks, ceftriaxone and clindamycin for 6 weeks for antibacterial coverage with plan to repeat CT chest in 3 weeks. DISCUSSION: We use tocilizumab for COVID 19 patients requiring invasive or non invasive mechanical ventilation and CRP ≥7.5 and exclude patients with ANC <2000, platelet <50,000 and history of serious bacterial, fungal or viral infection. This patient did not have any exclusion criteria but developed invasive fungal infection 3-4 weeks later. Due to worsening hypoxia and high D dimer, initial consideration was pulmonary embolism for which CT angiogram was done and a cavitary lesion was found. Differentials were bacterial abscess, tuberculosis or fungal infection. BAL played a crucial role in diagnosing aspergillosis. CONCLUSIONS: In patients presenting with worsening respiratory symptoms post tocilizumab administration we must keep a low index of suspicion for superimposed opportunistic infections including aspergillosis. Appropriate workup including CT chest, sputum or bronchoalveolar lavage for cultures (bacterial, fungal), Beta D Glucan and fungal panel is essential for diagnosis. Reference #1: Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia Ivan O Rosas;Norbert Bräu;Michael Waters;et al. New England Journal of Medicine, v384 n16 (20210422): 1503-1516 Reference #2: Pulmonary aspergillosis: a clinical review M. Kousha, R. Tadi, A.O. Soubani European Respiratory Review 2011 20: 156-174;DOI: 10.1183/09059180.00001011 Reference #3: Interleukin-6 Inhibitors. Available at: https://www.covid19treatmentguidelines.nih.gov. DISCLOSURES: No relevant relationships by Shaylika Chauhan No relevant relationships by Vipul Gidwani