Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Lung Aspergillus niger infection after SARS-CoV2

A 64-year-old never-smoker man, with professional exposure, presented to Marius Nasta Pneumophtisiology Institute for fatigability to effort, in the context of severe SARS-COV2 infection one month previously. His medical history includes pulmonary tuberculosis (55 years ago) and newly diagnosed type II diabetes (261 mg/dL glycemia). The thoracic tomography computer in the immediate post-COVID period (Fig. 1A) revealed the presence of glass ground lesions and a 3 cm nodule with cystic degeneration in the upper left lobe. A gross examination of the specimen identified a condensation area of 2.5 cm diameter, brown-grey colored, with necrosis and central ulceration. Microscopic examination showed the presence of bronchiectasis with squamous metaplasia of the epithelium, which appears ulcerated;numerous calcium oxalate crystals with adjacent foreign body granulomatous reaction;endobronchial are present fibrinous and inflammatory debris, brown-black pigment, and septate, dichotomous branching hyphae, suggestive of Aspergillus spp. A periodic acid-Schiff stain was performed, identifying the fungal hyphae. The histopathological diagnosis was bronchiectasis supra-infected and colonized with fungal filaments (Aspergillus niger).

Synthesis and evaluation of imidazole-bearing chalcones as a potential treatment for pulmonary aspergillosis

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.

Synthesis of new 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole derivatives as potential cytotoxic and antimicrobial agents

Globally cancer is the second leading cause of death;a drug that can cure cancer with the utmost negligible side effects is still a distant goal. Due to increasing antibiotic resistance, microbial infection remains a grave global health security threat. The ongoing coronavirus pandemic increased the risk of microbial and fungal infection. A new series of 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole (7a-t) have been synthesized. The structure of synthesized compounds was confirmed by the spectrometric analysis. The newly synthesized compounds were screened for cytotoxic activity against breast cell lines MCF-7 and MDA-MB-231. Against the MCF-7 cell line compounds 7f, 7 g and 7n showed excellent activity with GI50 0.6 muM to <100 nM concentration. Compound 7b showed good activity against MDA-MB-231 cell line with GI50 47 muM. The active derivatives 7b, 7e, 7f, 7 g and 7n were further evaluated for cytotoxicity against the epithelial cell line derived from the human embryonic kidney (HEK 293) and were found nontoxic. The thiazolyl-1,2,4-oxadiazole derivatives were also screened to evaluate theirs in vitro antimicrobial potential against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). Amongst the 7a-t derivatives, six compounds 7a, 7d, 7f, 7n, 7o, 7r showed good antifungal activity against C. albicans and eight compounds 7c, 7d, 7 g, 7h, 7i, 7k, 7l and 7o showed good activity against A. niger. The potential cytotoxic and antifungal activity suggested that the thiazolyl-1,2,4-oxadiazole derivatives could assist in the development of lead compounds for the treatment of cancer and microbial infections.Copyright © 2022 The Authors

vasive aspergillosis in patients with COVID-19 in intensive care units: sults of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Case series of invasive lung infections by Aspergillus species and zygomycosis among post COVID-19 and post-transplant individuals.

Airborne pathogens like Aspergillus bring the lungs in the frontline for defense. Pulmonary diseases caused by Aspergillus species are broadly classified as aspergilloma, chronic necrotizing pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA), and bronchopulmonary aspergillosis. Intensive care unit (ICU) admission is required for a large number of patients associated with IPA. It is not yet known whether patients with coronavirus disease 2019 (COVID-19) are at a similar risk for IPA as for influenza. However, usage of steroids plays a leading role in COVID-19. The family Mucoraceae includes filamentous fungi of the order Mucorales, causing a rare opportunistic fungal infection known as mucormycosis. The most commonly reported clinical presentations of mucormycosis are rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and others. Here, we report a case series of invasive pulmonary infection by various fungi like Aspergillus niger, Aspergillus fumigatus, Rhizopus oryzae, and Mucor species. Specific diagnosis was made based on microscopy, histology, culture, lactophenol cotton blue (LPCB) mount, and chest radiography and computed tomography (CT). To conclude, opportunistic fungal infections like those due to Aspergillus species and mucormycosis are most commonly associated with hematological malignancies, neutropenia, transplant patients, and diabetes. Therefore, early diagnosis by direct microscopy, surgical interventions, and effective antifungal treatment form the ideal management for invasive fungal infections like aspergillosis and mucormycosis, instead of waiting for the culture reports.

Subretinal Aspergillus Abscess in Post COVID-19 Recovered Patients - An Emerging Problem.

PURPOSE: To describe endogenous endophthalmitis in the setting of Covid-19 pneumonia post recovery. METHODS: Retrospective review of five patients of endogenous endophthalmitis following Covid-19 disease done. RESULTS: All five cases had received systemic corticosteroid for a mean duration of 7 days during severe Covid-19 treatment. Decrease vision was presenting symptom between 1 and 31 days following Covid-19 recovery. All patients had presumed fungal endogenous endophthalmitis based on clinical profile. Four out of five patients subjected to pars plana vitrectomy had microbiologically proven aspergillus species endogenous endophthalmitis on vitreous fluid assessment; two cases each of aspergillus niger and aspergillus fumigates. Four eyes underwent pars plana vitrectomy with silicone oil injection had shown satisfactory anatomical outcome with control of the infection; however, no significant visual gain achieved. CONCLUSION: We reported five cases of aspergillus endogenous endophthalmitis in Covid-19 recovered patients to document the likely presentation of this rising entity and avoid misdiagnosis.

Epidemiology of aspergillosis in Kuwait: A nationwide study

Objectives: Aspergillus is the most common filamentous fungi involved in human infections.It is characterized by causing various forms of clinical presentations, ie, invasive, chronic, and allergic forms. It is associated with considerable morbidity and mortality. In spite of this, the epidemiology of Aspergillus infections is scarce in Kuwait. This study aims to describe the epidemiology of aspergillosis in Kuwait on a national scale. Method(s): This is a 2-year retrospective observational study designed to analyze the demographic and mycological data on all Aspergillus isolates derived from clinical samples processed or submitted to the Mycology reference laboratory (MRL) by all government microbiology laboratories in Kuwait. Using the Mycology reference laboratory surveillance system, the required data was collected. It covers patients' age, gender, type of clinical samples, care settings (outpatient, wards, or ICU), the name of the Aspergillus species, and antifungal susceptibility for Aspergillus fumigatus.Species-level identification of Aspergillus was mostly based on morphological characteristics, except in a few cases where MALDI-T OF or PCR-sequencing of rDNA were performed. Antifungal susceptibility testing was done using Etest method according to manufacturer instructions. EUCAST clinical breakpoints were followed for the interpretation of antifungal susceptibility results for A. fumigatus species. Result(s): In total, 327 Aspergillus isolates from 277 patients were found.A total of 34/277 patients had 2 or more samples yielding either the same Aspergillus spp. (n = 17) or a different species (n = 17). The most prevalent type of clinical specimens was respiratorysample (n =196,60%), followed byear swabs (n= 64,19.6%), and nails (n= 24,7.3%). A.niger (n=147) was the most isolated species, involving 45% of aspergillosis cases followed by four other species including A. fumigatus (n = 64), A.flavus (n = 55), A.terreus (n = 38), and A.nidulans (n = 13).A total of 10 cases were caused by rare Aspergillus spp.All A. fumigatus isolates were susceptible to voriconazole. Itraconazole also exhibited excellent in vitro activity against nearly all A. fumigatus except 4 isolates that were resistant. Conclusion(s): This study reveals the epidemiology of aspergillosis from several perspectives. It gives some insights on the burden of Aspergillosis in Kuwait, especially during the COVID-19 pandemic. Respiratory samples were the predominant positive samples suggesting high rates of pulmonary aspergillosis. A. niger, not A. fumigatus or A. flavus, is the most prevalent agent of aspergillosis in Kuwait.Azole resistance is rare among A.fumigatus.Further studies are needed to explore the spectrum of clinical presentations with special emphasis on pulmonary aspergillosis.

Otitis with Aspergillus niger in a patient with SARS-CoV-2 and multiple comorbidities

Introduction. COVID-19 is associated with a significant incidence of bacterial and fungal superinfections and with the exacerbation of pre-existing infections, representing a diagnostic and therapeutic challenge. Case presentation. A 64-year-old woman, confirmed with COVID-19 by the SARS-CoV-2 antigen test, is hospitalized accusing fatigue, nausea, watery stools, cough and vertigo started 10 days ago, aggravated 4 days before the pres-entation. It also reports recurrent episodes of otalgia and otorrheic pluriantibiotic treatment in the last 2 months. From the personal pathological antecedents we remember: hypothyroidism, dyslipidemia, hypertension, ischemic heart disease, history of deep vein thrombosis (DVT) and secondary pulmonary thromboembolism, in chronic anticoagulant treatment. Pathological clinical signs at admission: bilateral basal crackling rales. Biologically, inflam-matory syndrome is detected, and radiologically, interstitial-alveolar infiltrates in the lower lung fields. On day 3 of hospitalization, the patient shows purulent secretion in the right external auditory canal and the ENT consultation confirms chronic suppurative otitis media in acute onset. Bacteriological examination of otic secretion reveals As-pergillus niger. Antiviral treatment with Remdesivir is initiated, antibiotic therapy initiated at home with Azithro-mycin is continued for one day, then escalated to Ceftriaxone i.v. (in the context of clinical-paraclinical aggravation), systemic corticotherapy, anticoagulation with Dalteparin in the prophylactic regime of DVT, systemic treatment with Voriconazole p.o. (according to the antifungal program) and topical (local) with a slow favorable evolution. Conclusions. The association of COVID-19 with otitis with Aspergillus is a rare and particular clinical picture. © 2021, Amaltea Medical Publishing House. All rights reserved.

WELL, THAT ESCALATED RATHER QUICKLY: A CASE OF RAPIDLY PROGRESSIVE SUBACUTE INVASIVE PULMONARY ASPERGILLOSIS

SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pulmonary Aspergillus infection has a wide array of manifestations. Chronic Pulmonary Aspergillosis is an uncommon progressive respiratory disease, with the Subacute Invasive Pulmonary Aspergillosis form, one of the most challenging to manage. Typically it presents with rapidly progressive infection (of less than 3 months) in mild to moderately immunocompromised patients with underlying structural lung disease. We herein report the case of a 69-year old female with post-tuberculous cavity with disease progression, in approximately 6 weeks, associated with Aspergillus infection. CASE PRESENTATION: Patient is a 69-year old African American female, never smoker, with known history of Type 2 Diabetes Mellitus and previously treated mycobacterium tuberculosis with residual small right upper lobe cavity (measuring approximately 35 x 40 mm). She was being followed in our outpatient thoracic oncology clinic with serial imaging for surveillance, CT Chest initially every 3 - 6 months then annually thereafter with PET scan as clinically indicated. The cavity remained relatively unchanged for approximately 5 years. In October 2021, her CT Chest had revealed a stable cavity, even despite SARS-CoV-2 Pneumonia infection the previous year. The following month she was admitted to an outside hospital for hyperglycemia with notable significant increase in size of the right upper lobe cavity to 69 x 72 mm with surrounding nodularity. She completed a course of antibiotics and was seen in our clinic 3 months post discharge with a repeat CT Chest which now revealed a mass like area of consolidation with large area of lucency and superimposed fungus ball (now measuring 80 mm x 70mm). She underwent Electromagnetic Navigational Bronchoscopy with transbronchial biopsy and right upper lobe bronchoalveolar lavage. BAL culture identified Aspergillus niger, with no other pathogens (including acid fast bacilli isolated) or malignant cells observed. Biopsy revealed marked mixed inflammation and fungal hyphae. Patient is currently undergoing long-term oral antifungal therapy with plan for close surgical follow-up. DISCUSSION: The diagnosis of Chronic Pulmonary Aspergillosis requires a combination of clinical, radiological and histopathological characteristics present for atleast 3 months for diagnosis. This includes the presence of one or more cavities on thoracic imaging, evidence of aspergillus infection or an immunological response to aspergillus as well as excluding alternative diagnoses. Advances in diagnostic tools have improved early diagnosis and subsequent management as noted in our case. Surgical resection is recommended for simple aspergilloma, however rapidly progressive disease processes are recommended to be managed as invasive aspergillosis. CONCLUSIONS: Post-tuberculosis chronic pulmonary aspergillosis is an emerging disease with significant associated morbidity and likely health burden. Reference #1: Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management David W. Denning, Jacques Cadranel, Catherine Beigelman-Aubry, Florence Ader, Arunaloke Chakrabarti, Stijn Blot, Andrew J. Ullmann, George Dimopoulos, Christoph Lange European Respiratory Journal Jan 2016, 47 (1) 45-68;DOI: 10.1183/13993003.00583-2015 Reference #2: Bongomin F. Post-tuberculosis chronic pulmonary aspergillosis: An emerging public health concern. PLoS Pathog. 2020;16(8):e1008742. Published 2020 Aug 20. doi:10.1371/journal.ppat.1008742 DISCLOSURES: No relevant relationships by Omotooke Babalola No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Sulaiman Tijani

POST-COVID-19 ASPERGILLOSIS

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

CALCIUM OXALATE DEPOSITION IN PULMONARY ASPERGILLOSIS

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

Atypical Presentation of Aspergillus niger Infection in the Oral Cavity as a Prediction of Invasive Pulmonary Aspergillosis in a Patient with COVID-19: Case Report and Literature Review.

Coinfections between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens such as Aspergillus have become challenging, as well as being associated with high morbidity and mortality in patients with COVID-19. Aspergillus niger is a common environmental mold. Before the emergence of COVID-19, it was considered a very rare cause of invasive pulmonary aspergillosis (IPA), occurring mainly in immunocompromised patients. The aim of this study was to describe a very rare case of IPA caused by A. niger found in the oral cavity of a mechanically ventilated COVID-19 patient. A. niger detected in the gingival pocket was diagnosed earlier than in the bronchial lavage, and without treatment, passed into the lungs of the patient, causing serious complications. The swab from the oral cavity of mechanically ventilated COVID-19 patients can be a predictor of the subsequent severity of inflammatory lesions and the development of suspected IPA.

Incidence of Collar Rot of Groundnut in Rajasthan and its Management

Background: Groundnut (Arachis hypogaea L.) is an important legume crop of tropical and sub-tropical areas of the world. This crop suffers from several diseases like early leaf spot, late leaf spot, rust, groundnut bud necrosis, peanut clump and collar rot etc. But collar rot caused by Aspergillus niger van Teighem is one of the most important seed and soil borne diseases causing huge economic (40-50 per cent) loss in India and abroad. Methods: A roving survey was conducted to assess the incidence of collar rot in eight major groundnut growing districts of western Rajasthan i.e. Bikaner, Jodhpur, Churu, Jalore, Jaipur, Sikar, Nagaur and Dausa during Kharif 2018. A field experiment was carried out for two consecutive years (2019 and 2020) to manage the disease through altering micro-climate under canopy with six levels of seed rates (80, 85, 90, 95, 100 and 105 kg/ha). Result: Our investigations cleared that this disease is prevalent in all the 200 fields surveyed in eight districts of Rajasthan with 22.99 per cent overall disease incidence which varied from 17.84 to 32.38 per cent with monetary losses. Maximum disease incidence was recorded in Jaipur (28.85%) district while it was lowest in Nagaur district (20.15%). Higher disease reduction (12.97%) with increased pod yield (27.65%) was observed with higher seed rate of 105 kg/ha as compared to standard recommended seed rate (80 kg/ha) as this pathogen is favoured by higher temperature and low soil moisture, dense canopy provides shade that increases humidity under the cropped area and lowers temperature. As a result of this, plant mortality can be compensated by increasing plant population through seed rate, as it modifies the microclimate and generate an environment which is less favourable for developing collar rot disease of groundnut. [ FROM AUTHOR] Copyright of Legume Research: An International Journal is the property of Agricultural Research Communication Centre and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

UV-LEDs Based Photocatalytic Cabin IAQ System to Eliminate Viruses Encountered in a Conditioned Space

The author has been conducting research on UV based photocatalytic air purifier systems for the past 5 years to eliminate living organic germs, bacteria, pathogens, etc. from the cabin air. An HVAC system has been developed by using a filter impregnated by titanium di-oxide (TiO2) with UV lights to improve and maintain cabin air quality. The designed system can be used for conventional vehicles, EVs, ride sharing and for autonomous vehicles. The author has designed and constructed a 3rd generation HVAC unit for cabin air purification for automobiles that is based on UV photocatalytic process by using UV-C LEDs to eliminate viruses that typically exist in conditioned space. The author has conducted tests with the following viruses and bacteria that are typically encountered in a conditioned environment:(i)Staph Epidermititus: Infections in wounds (Anthrax)(ii)Erwinia Herbicola: Bacteria (Infection in soil and water)(iii)MS2: RNA, COVID-19(iv)Phi-174: DNA, Herpes and HIV(v)Bacillus Globigii: Virus - influenza(vi)Aspergillus Niger: Mold spore (Black mold) Percentage destruction rates for the above viruses and bacteria at 15, 30, 45 and 60 minute intervals are presented in this paper. The developed system is able to reduce the viruses by almost 99.99#x00025;(log 4 reductions) in first 15 minutes of unit operation. Aspergillus Niger destruction rates were lower - approx. 90.3#x00025;in 15 minutes (log 1 reduction). The developed system out performs the industry standard of log 4 reductions in 60 minutes! Using a UV-C and UV-A LED light sources with titanium dioxide filter makes this a unique application for automobile HVAC systems. Additional tests have been planned in 2022 to ensure the developed system is able to eliminate Omicron, a variant of COVID-19. © 2022 SAE International. All Rights Reserved.

Invasive Pulmonary Aspergillosis after COVID-19 Pneumonia.

COVID-19 emerged in China in late 2019 and quickly spread worldwide. The severe immunomodulation and depletion of lymphocytes caused by the virus and its therapy led to an increase in the incidence of superinfections. COVID-19-associated pulmonary aspergillosis (CAPA) is a new entity with increasing incidence and high associated mortality. We present the case of a 68-year-old patient admitted to our ward after recovering from severe COVID-19 pneumonia. Due to worsening of her clinical condition, chest computed tomography was performed and a lung abscess was documented with the identification of Aspergillus niger. Despite therapy with voriconazole, the patient's condition deteriorated, culminating in her death. LEARNING POINTS: COVID-19-associated pulmonary aspergillosis (CAPA) is a new entity with an increasing incidence.It is a serious and life-threatening complication in patients with severe COVID-19 even in the absence of the classic risk factors for invasive pulmonary aspergillosis.Clinical suspicion is crucial since a timely diagnosis and treatment have a major impact on prognosis.

Clinical Characteristics of Critically Ill Patients with COVID-19 and Invasive Pulmonary Aspergillosis: A Case Series from Mexico City

Background. COVID-19 has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in case series of critically ill patients. However, the criteria for CAPA diagnosis has been inconsistent among most of the reports. Mexico has been widely affected by SARS-CoV-2. We present a series of CAPA cases at a teaching hospital in Mexico City. Methods. We performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from May 1st, 2020, to May 1st, 2021. Including only those with critical COVID-19 who required invasive mechanical ventilation (IMV). Patients with a diagnosis of CAPA were analyzed. We followed the 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika). Results. Among the 230 admitted patients who required IMV, we identified 49 (21.3%) cases of CAPA, 46 probable CAPA and 3 proven CAPA. Nineteen (38%) of those died in the hospital. The mean age was 64.5 ± 12.6 years and 11 were female. Proven CAPA was diagnosed with culture in three cases (one A. niger, one A. terreus and one A. fumigatus). Probable CAPA was diagnosed by a positive serum GP in 27 (55.1%) patients and by a positive bronchoalveolar lavage (BAL) GP in 29 (59.2%) cases. Seven patients had both serum and BAL positive GP. Forty-six (93.9%) patients received corticosteroids, and 22 (49.9%) were treated with tocilizumab before CAPA diagnosis. All but one received isavuconazole as CAPA treatment. We detected 35 (71.4%) patients who had a bacterial co-infection. Eighteen of those died (51.4%) compared to only one dead in the subgroup without coinfections (7.1%). The mean time from hospital admission to CAPA diagnosis was 6.2 days (SD 7.1) among those who survived compared to 13.2 (SD 6.3) days in those who died p< 0.01. Conclusion. CAPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality when it occurs with other bacterial coinfections and when it is diagnosed late from admission.

Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study.

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.

Possible COVID-19-Associated Pulmonary Aspergillosis Due to Aspergillus niger in Greece.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm "BM-AspICU" for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 µg/mL, for itraconazole and posaconazole 0.25 µg/mL, for voriconazole 0.5 µg/mL, for flucytosine 4 µg/mL, for amphotericin B 1 µg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 µg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient's unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain.

Mixed etiology COVID-19 associated acute rhinosinusitis caused by two Aspergillus species.

INTRODUCTION: Acute invasive fungal rhino-sinusitis (AIFR) is a life-threatening infection that is mostly found in immunocompromised patients with serious morbidity and mortality. Recently, reports of AIFR have also emerged among SARS-CoV-2 infected patients. CASE PRESENTATION: A 50-year-old diabetic woman, previously diagnosed with COVID-19 pneumonia, was presented to the hospital with left facial pain on day 12 after discharge. Paranasal sinuses computed tomography was performed and according to the mucosal thickening in both maxillary sinuses and ethmoidal air cells, the patient underwent functional endoscopic sinus surgery (FESS) and necrosis were observed. The histopathologic examination revealed mycelium with septation suspected to Aspergillus and the culture was consistent with Aspergillus flavus and also Aspergillus niger . We reported a case of COVID-19 associated AIFR with two combined Aspergillus species from Iran. The patient received liposomal amphotericin B, which then switched to voriconazole combined with aggressive surgical debridement of necrotic tissues with a clinically favorable outcome. CONCLUSION: Mixed etiology AIFR can influence the outcome. However, further investigation is required upon this new threat.