Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 38
Filter
1.
American Journal of Transplantation ; 22(Supplement 3):908-909, 2022.
Article in English | EMBASE | ID: covidwho-2063435

ABSTRACT

Purpose: To determine if Apadenoson or Regadenoson has a therapeutic effect in attenuating hyper-inflammation and improving survival rate in K18-hACE2mice or Syrian hamsters infected with SARS-CoV-2. Method(s): 6-8 weeks old male K18-hACE2mice were divided into Control group that received vehicle;Test group 1 that received the drug (Apadenoson or Regadenoson) 24hrs prior to challenge with SARS-CoV-2;and Test Group 2 (Drug-delay), that received the drug with a 5 hr delay post-viral infection (n=6/grp). Viral dose was 1250 PfuHong Kong/VM20001061/2020 delivered via intranasal route. Drug was delivered subcutaneously using 1007D ALZET pumps. 6 weeks old Syrian hamsters were divided into Control group that received Vehicle and Virus (n=4) and 2 test groups (n=5/group) that received Apadenoson+Virus and Regadenoson+Virus. Drugs were delivered by 2ML2 ALZET pumps (4ug/kg/hr). Hamsters were inoculated intratracheally with 750PFU SARS-CoV-2 WA1 strain prior to treatment. Mice were weighed and clinical scores recorded daily. Bronchoalveolar lavage fluid (BALF) and serum were collected along with lungs. Plethysmography was done on days 0, 2, 4 and 7. Result(s): Apadenoson administered post-infection was efficacious in decreasing weight loss, improving clinical score, and increasing the survival rate in K18-hACE2 mice, i.e. 50% survival was observed at Day 5 and at Day 7 post-infection for drug given before or after infection respectively. Apadenoson given post-infection improved the histopathology that was observed in the vehicle control group, decreased pro-inflammatory IL-6, IFN-gamma, MCCP-1, MIP-1beta, IP-10, and Rantes in serum, increased anti-inflammatory Ang1-7 levels, and decreased monocytes in BALF. 42% of mice that received Regadenoson pre-challenge survived infection compared to 6.25% in the vehicle or Drug delay (drug given post-infection) groups. Viral titers in the lungs of Regadenoson-treated mice were found decreased. Treatment also significantly decreased CD4+, CD8+T cells, eosinophils, and neutrophils in BALF. Plethysmography, in hamsters, showed significant improvement of pulmonary function parameters, Rpef and PenH, following treatment with Apadenoson given post-infection. Apadenoson cleared the virus from BALF and maintained Ang1-7 levels. Both drugs decreased plasma IFN-gamma levels. Conclusion(s): Treatment with Apadenoson attenuated inflammation, improved pulmonary function, decreased weight loss, and enhanced survival rate following infection with SARS-CoV-2 virus. The results demonstrate the translational significance of Apadenoson in the treatment of COVID-19.

2.
American Journal of Transplantation ; 22(Supplement 3):572, 2022.
Article in English | EMBASE | ID: covidwho-2063393

ABSTRACT

Purpose: To study the clinical application of metagenomic next-generation sequencing (mNGS) in the detection of viral infections in kidney transplant recipients (KTRs) during the COVID-19 pandemic. Method(s): Using mNGS techniques, 50 human fluid samples of KTRs were detected in Henan Province People's Hospital between May 2020 to May 2021, including 20 bronchoalveolar lavage fluid (BALF) samples, 21 urine samples and 9 blood samples. The detected nucleic acid sequences were compared and analyzed with the existing viral nucleic acid sequences in the database, and the virus infection spectrum of KTRs was drawn. Result(s): The viral nucleic acids of 15 types of viruses were detected in 96.00% (48/50) of the samples, of which 11 types of viruses were in BALF (95.00%, 19/20), and the dominant viruses were torque teno virus (TTV) (65.00%;13/20), cytomegalovirus (CMV) (45.00%;9/20) and human alphaherpesvirus 1 (25.00%;5/20). 12 viruses (95.24%, 20/21) were detected in the urine, and the dominant viruses were TTV (52.38%;11/21), JC polyomavirus (52.38%;11/21), BK polyomavirus (42.86%;9/21), CMV (33.33%;7/21) and human betaherpesvirus 6B (28.57%;6/21). 7 viruses were detected in the blood (100.00%, 9/9), and the dominant virus was TTV (100.00%;9/9). Four rare viruses were detected in BALF and urine, including WU polyomavirus, primate bocaparvovirus 1, simian virus 12, and volepox virus. Further analysis showed that TTV infection with high reads indicated a higher risk of acute rejection (P<0.05). Conclusion(s): mNGS detection reveals the rich virus spectrum of infected persons after kidney transplantation, and improves the detection rate of rare viruses. TTV may be a new biomarker for predicting rejection. (Figure Presented).

3.
Chest ; 162(4):A2241, 2022.
Article in English | EMBASE | ID: covidwho-2060916

ABSTRACT

SESSION TITLE: Pulmonary Manifestations of Infections SESSION TYPE: Case Reports PRESENTED ON: 10/17/2022 03:15 pm - 04:15 pm INTRODUCTION: Diffuse alveolar hemorrhage (DAH) due to an undiagnosed autoimmune condition is rare and can be life-threatening. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been described as a viable rescue therapy in severe cases, providing time to establish a diagnosis and begin remission induction therapy (1). We report a patient who presented during the Omicron surge with hypoxemic respiratory failure due to pulmonary hemorrhage ultimately diagnosed with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) who was supported with VV-ECMO without systemic anticoagulation. CASE PRESENTATION: A 46-year-old woman presented with subacute fatigue and two days of cough and brown sputum. She was found to have normocytic anemia (hemoglobin 3.5 g/dL), renal failure (serum creatinine 17.4 µmol/L), and bilateral pulmonary infiltrates on chest roentgenogram. Though vaccinated, nasal molecular testing detected SARS-CoV-2. She was intubated for progressive hypoxic respiratory failure and bronchoalveolar lavage fluid was consistent with DAH. She received empiric antibiotics, remdesivir, and pulse dose intravenous methylprednisolone as well as continuous renal replacement therapy and plasma exchange. Due to refractory hypoxemia she was cannulated for VV-ECMO. Systemic anticoagulation was deferred due to concerns that it may exacerbate her underlying pathology and due to a small subcortical bleed seen on computed tomography of the head. Perinuclear ANCA (titer >1:1280) was confirmed by immunofluorescence analysis with elevated myeloperoxidase serologies and cyclophosphamide was initiated. Glomeruli with cellular crescent formation consistent with AAV was later identified on renal biopsy. Her course was complicated by recurrent DAH while tapering steroids and an iliac vein thrombus, extracted during decannulation. Her respiratory failure resolved and she was discharged to rehab. DISCUSSION: Traditionally, VV-ECMO obligates systemic anticoagulation to prevent circuit thrombosis, however this may be viewed as a barrier to its use in patients with prohibitive bleeding risk and may contribute to the therapy's overall morbidity. Some institutions have begun to demonstrate the safety of ECMO with low- or prophylactic doses of anticoagulation (2), but this practice remains controversial. Detection of SARS-CoV-2 posed diagnostic and management challenges and its significance to this case remains uncertain. There are many past examples of infectious triggers for both DAH and AAV, and there is emerging evidence for an association between SARS-CoV-2 and ANCA (3). Concerns regarding the risk of B-cell depletion influenced the selection of remission induction therapy. CONCLUSIONS: In the case described, a patient with severe DAH was successfully supported with VV-ECMO. Withholding systemic anticoagulation did not prevent recurrent bleeding and may have contributed to a deep vein thrombosis. Reference #1: Arnold S, Deja M, Nitschke M, Bohnet S, Wallis S, Humrich JY, Riemekasten G, Steinhoff J, Lamprecht P. Extracorporeal membrane oxygenation in ANCA-associated vasculitis. Autoimmun Rev. 2021 Jan;20(1):102702. doi: 10.1016/j.autrev.2020.102702. Epub 2020 Nov 11. PMID: 33188916. Reference #2: Kurihara C, Walter JM, Karim A, et al. Feasibility of Venovenous Extracorporeal Membrane Oxygenation Without Systemic Anticoagulation. Ann Thorac Surg. 2020;110(4):1209-1215. doi:10.1016/j.athoracsur.2020.02.011 Reference #3: Kadkhoda, K., Laurita, K. Antineutrophil cytoplasmic antibodies and their association with clinical outcomes in hospitalized COVID-19 patients. Cell Death Discov. 7, 277 (2021). DISCLOSURES: No relevant relationships by Nathaniel Nelson No relevant relationships by Radu Postelnicu no disclosure on file for Antonio Velez;

4.
Chest ; 162(4):A623-A624, 2022.
Article in English | EMBASE | ID: covidwho-2060649

ABSTRACT

SESSION TITLE: Unusual Pneumonias SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Invasive pulmonary aspergillosis (IPA) commonly occurs in the setting of immunosuppression. Underlying lung disease is a well-known risk factor for IPA;however, interstitial lung disease (ILD) has not been recognized as a risk factor for IPA[1]. CASE PRESENTATION: A 40-year-old male with a history of a failed kidney transplant now on hemodialysis (HD), Juvenile Rheumatoid Arthritis, Mixed Connective Tissue Disease, Aspergilloma led to right lower lobectomy a year ago, COVID-19 infection three months ago, chronic lung disease (CLD) thought to be due to Nonspecific interstitial pneumonia (NSIP) presented with dyspnea. He had several hospitalizations for respiratory failure needing intubation or NIPPV, broad-spectrum antibiotics, steroids, and HD with improved respiratory status, eventually discharged. Bronchoalveolar lavage fluid culture grew aspergillus terreus but was negative for Pneumocystis (PCP), bacteria, acid-fast bacilli, and Nocardia. The transbronchial biopsies showed mixed inflammatory type and fungal forms in one specimen. Additionally, the initially negative galactomannan converted into a serial rise in galactomannan (>3.75 Index) along with a rise in beta d-glucan (>500 pg/ml). Unfortunately, he had gaps in antifungals and was readmitted similarly. Micafungin was added for dual fungal coverage and was planned for surgical lung biopsy to characterize ILD further once his respiratory status allows. DISCUSSION: He has multiple risk factors for developing IPA, such as high-dose steroids for ILD and recent COVID infection. Initially, respiratory failure was thought to be due to exacerbation of ILD, and suspicion for IPA was low because of lack of neutropenia, negative fungal biomarkers, lack of classic findings on lung imaging, and in-hospital clinical improvement with steroids. However, the eventual course of recurrent respiratory failure while on high-dose steroids, along with gaps in antifungal therapy and continued growth of Aspergillus, made IPA the most likely diagnosis. For IPA, the mainstay of treatment is both adequate antifungal therapy and reduction in immunosuppression to the extent possible[2];however, it is unclear if his underlying ILD can tolerate steroid taper. He will need a lung transplant after adequately treating IPA. CONCLUSIONS: There are no current guidelines on simultaneously treating IPA and NSIP. It is challenging to balance reduction in immunosuppression as tolerated for ILD and concurrently maintain antifungal therapy. During this patient's hospitalization, there have been considerations of using a steroid-sparing agent for his suspected NSIP, however, in the setting of active infection, its benefit is debatable.[3] Reference #1: Matsuyama H, Miyoshi S, Sugino K, et al. Fatal Invasive Pulmonary Aspergillosis Associated with Nonspecific Interstitial Pneumonia: An Autopsy Case Report. Intern Med. 2018;57(24):3619-3624. doi:10.2169/internalmedicine.1144-18 Reference #2: Thomas F. Patterson, George R. Thompson, III, David W. Denning, Jay A. Fishman, Susan Hadley, Raoul Herbrecht, Dimitrios P. Kontoyiannis, Kieren A. Marr, Vicki A. Morrison, M. Hong Nguyen, Brahm H. Segal, William J. Steinbach, David A. Stevens, Thomas J. Walsh, John R. Wingard, Jo-Anne H. Young, John E. Bennett, Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 63, Issue 4, 15 August 2016, Pages e1–e60, https://doi.org/10.1093/cid/ciw326 Reference #3: Mezger, M., Wozniok, I., Blockhaus, C., Kurzai, O., Hebart, H., Einsele, H., & Loeffler, J. (2008). Impact of mycophenolic acid on the functionality of human polymorphonuclear neutrophils and dendritic cells during interaction with Aspergillus fumigatus. Antimicrobial agents and chemotherapy, 52(7), 2644–2646. https://doi.org/10.1128/AAC.01618-07 DISCLOSURES: No relevant relationships by Nasir Alhamdan No relevant relati nships by Parth Jamindar No relevant relationships by Harshitha Mergey Devender No relevant relationships by Abira Usman No relevant relationships by Vishruth Vyata

5.
Chest ; 162(4):A351-A352, 2022.
Article in English | EMBASE | ID: covidwho-2060571

ABSTRACT

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Coccidioidomycosis caused by the fungi C. immitis and C. Posadasii is well known to be endemic to the Southwest United States. Less than 1% of these infections will manifest as extrapulmonary symptoms and multiple sites causing dissemination fungemia [1]. Risk factors for disseminated infection include exogenous immunosuppression, immunodeficiency, pregnancy, and ethnic backgrounds of African and Filipino descent [2]. CASE PRESENTATION: A 39-year-old previously immunocompetent Congolese male with recent onset of recurrent skin abscess, and positive testing for COVID-19 three week prior (not treated with steroids). He presents with shortness of breath, back pain, fevers after recently migrating from the Southwest region to the Midwest. Upon admission imaging with Computed Tomography (CT) revealed extensive pulmonary infiltrates (Fig 1), intra-abdominal abscesses, and magnetic resonance imaging revealing (MRI) osteomyelitis of the thoracic (Fig 2) and lumbar spine (Fig 3). His work of breathing continued to worsen, requiring prompt intubation, and he was initiated on a broad-spectrum antimicrobial regimen, including fluconazole, voriconazole, cefepime and vancomycin. Immunoglobulins, HIV and oxidative burst testing was unremarkable. Cultures from image-guided aspiration of the psoas abscess, incision, and drainages of skin abscess and bronchoalveolar lavage fluid were all positive for coccidioidomycosis, transitioned to amphotericin B. Course complicated with the development of multidrug-resistance pseudomonas aerogenes VAP treated with inhaled tobramycin and meropenem. He developed progressive acute respiratory distress syndrome with refractory hypoxemia. After 3 weeks of antimicrobial and anti-fungal treatment, a decision was made to transfer the patient to a lung transplant center, however, due to ongoing fungemia, he was deemed to be not a candidate for extracorporeal membrane exchange and lung transplantation. About a month into his hospitalization, the family decided to withdraw care. DISCUSSION: Reactivation of latent coccidiomycosis has been largely studied in the immunosuppressed population that includes HIV, hematological malignancies, and diabetes mellitus, however little is known about this fungal infection in the immunosuppressed state in the setting of COVID-19. Thus far only two case reports have been reported of co-infection if COVID-19 and pulmonary coccidioidomycosis [3]. The days of the COVID-19 pandemic might contribute to further delays in diagnosing this fungal infection due to similarities of pulmonary manifestation. CONCLUSIONS: This case demonstrates a COVID-19 infection leading to an immunosuppressed status resulting in disseminated infection from reactivation of latent coccidiomycosis. As a result, physicians must maintain a high level of suspicion for superimposed fungal infections in those with even relative immunosuppression from a recent COVID infection. Reference #1: Odio CD, Marciano BE, Galgiani JN, Holland SM. Risk Factors for Disseminated Coccidioidomycosis, United States. Emerg Infect Dis. 2017;23(2):308-311. doi:10.3201/eid2302.160505 Reference #2: Hector RF, Laniado-Laborin R. Coccidioidomycosis–a fungal disease of the Americas. PLoS Med. 2005;2(1):e2. doi:10.1371/journal.pmed.0020002 Reference #3: Shah AS, Heidari A, Civelli VF, et al. The Coincidence of 2 Epidemics, Coccidioidomycosis and SARS-CoV-2: A Case Report. Journal of Investigative Medicine High Impact Case Reports. January 2020. doi:10.1177/2324709620930540 DISCLOSURES: No relevant relationships by Stephen Doyle No relevant relationships by Connor McCalmon No relevant relationships by John Parent No relevant relationships by Jay Patel No relevant relationships by Angela Peraino No relevant relationships by Keval Ray

6.
BMC Complement Med Ther ; 22(1): 242, 2022 Sep 17.
Article in English | MEDLINE | ID: covidwho-2043124

ABSTRACT

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.


Subject(s)
Agaricales , Anti-Allergic Agents , Anti-Asthmatic Agents , Asthma , Phaeophyta , Shiitake Mushrooms , Aluminum Oxide/adverse effects , Animals , Anti-Allergic Agents/adverse effects , Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Asthma/drug therapy , Cytokines/metabolism , Immunoglobulin E , Inflammation/drug therapy , Interleukin-10 , Leukotriene C4/adverse effects , Mice , Mice, Inbred BALB C , Mycelium , Ovalbumin/adverse effects , Phaeophyta/metabolism , Prostaglandin D2/adverse effects , Shiitake Mushrooms/metabolism , Vascular Cell Adhesion Molecule-1/adverse effects
7.
13th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics, BCB 2022 ; 2022.
Article in English | Scopus | ID: covidwho-2029544

ABSTRACT

Bio-marker identification for COVID-19 remains a vital research area to improve current and future pandemic responses. Innovative artificial intelligence and machine learning-based systems may leverage the large quantity and complexity of single cell sequencing data to quickly identify disease with high sensitivity. In this study, we developed a novel approach to classify patient COVID-19 infection severity using single-cell sequencing data derived from patient BronchoAlveolar Lavage Fluid (BALF) samples. We also identified key genetic biomarkers associated with COVID-19 infection severity. Feature importance scores from high performing COVID-19 classifiers were used to identify a set of novel genetic biomarkers that are predictive of COVID-19 infection severity. Treatment development and pandemic reaction may be greatly improved using our novel big-data approach. Our implementation is available on https://github.com/aekanshgoel/COVID-19-scRNAseq. © 2022 Owner/Author.

8.
Journal of Hepatology ; 77:S691-S692, 2022.
Article in English | EMBASE | ID: covidwho-1996646

ABSTRACT

Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.

9.
Journal of General Internal Medicine ; 37:S501-S502, 2022.
Article in English | EMBASE | ID: covidwho-1995715

ABSTRACT

CASE: A 75-year-old male with history of sarcoidosis, heart failure, atrial fibrillation, hypertension, and mitral valve replacement presented to the emergency department with dyspnea and dry cough for one week. He endorsed fatigue and chills, but denied subjective fever, weight loss, edema, or congestion. Vitals were notable for a temperature of 100.3 F, respiratory rate of 25, and SpO2 of 82% on room air, which increased to 95% on 10 L of oxygen. Physical exam revealed clear lung sounds bilaterally without accessory muscle use. Labs showed a leukocytosis of 15.6, hemoglobin of 11.6, and pro-BNP of 631.2. ABG revealed compensated respiratory alkalosis. BMP, troponin, EKG, and COVID-19 PCR tests were all unremarkable. Of note, the patient had been on prednisone 10 mg daily for the past four years for sarcoidosis which was increased to 20 mg daily one month prior. After admission, further work-up revealed elevations in pro-calcitonin of 0.61, LDH of 396, and 1,3-beta-D-glucan of >500. Chest CT revealed bilateral scattered ground-glass opacities and underlying evidence of chronic interstitial disease. The patient was continued on a higher dose of prednisone 40 mg twice daily and started on atovaquone 750 mg twice daily for empiric Pneumocystis jiroveci pneumonia (PJP) therapy. Unfortunately, he continued to deteriorate and required intubation. His bronchoalveolar lavage fluid returned positive for Pneumocystis jiroveci by DFA. The patient was started on high- dose TMP-SMX. However, he developed DIC, bilateral upper extremity DVTs, and hyperkalemia thought to be secondary to TMP-SMX. The family decided to withdraw care and the patient passed. IMPACT/DISCUSSION: The role of Pneumocystis jiroveci pneumonia (PJP) prophylaxis in non-HIV patients on chronic steroids remains poorly elucidated and lacks evidence in literature. While some experts support prophylaxis for those on daily prednisone equivalents of greater than 20 mg for over 4 weeks, others suggest that daily prednisone equivalents of greater than 30 mg for over 12 weeks should warrant prophylaxis. We describe a patient with sarcoidosis who was on 20 mg of daily prednisone for over 4 weeks without PJP prophylaxis and subsequently died while battling PJP. Nearly 53% of PJP infections occur in nonHIV patients. Studies in patients with leukemia or organ transplant have shown that PJP prophylaxis with TMP-SMX decreases PJP occurrence by 85% and PJP-related mortality by 83%. The scarcity of literature on the use of PJP prophylaxis, particularly in those with chronic lung diseases such as sarcoidosis that require prolonged steroids, impedes timely consideration of PJP prophylaxis and poses a significant risk to these patients. CONCLUSION: We describe a patient with sarcoidosis on chronic steroids who subsequently developed a fatal case of PJP. Our case highlights the need to consider PJP as a differential diagnosis in non-HIV patients on steroids, and more importantly, to consider PJP prophylaxis in these individuals.

10.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927904

ABSTRACT

Background: There is a paucity of therapies for acute lung injury (ALI) induced by respiratory viruses. A previously demonstrated key mechanism of ALI, particularly in the setting of severe acute respiratory syndrome coronavirus infections, has been ascribed to decreased cell surface angiotensin converting enzyme 2 (ACE2) leading to increased circulating levels of angiotensin II (Ang2). In turn, supraphysiological Ang2 levels trigger a cascade of events that culminates with endothelial injury in the systemic circulation via acid sphingomyelinase (ASMase) activation. ASMase has been implicated in several models of ALI, but its specific involvement in Ang2-induced ALI is unknown. ASMase hydrolyzes sphingomyelin to pro-apoptotic, edemagenic ceramide, which can be metabolized to endothelial-protective sphingosine-1-phosphate (S1P). Therefore, the ratio of ceramide/S1P can determine endothelial cell fate and lung vascular permeability. We hypothesized that ceramide levels are increased relative to S1P in mice with Ang2-induced ALI. Methods: Following a published protocol of Ang2-induced ALI (Wu et al, 2017), we delivered Ang2 via osmotic pumps (1 ug/kg/min, 7 days;Ang2-mice), using saline (sham) or untreated C57BL/6 mice as controls. We evaluated pulmonary function (FlexiVent);albumin, IgM (ELISA), and inflammatory cell abundance in bronchoalveolar lavage fluid (BALF);and lung parenchyma inflammation and fibrosis (Ashcroft score) on H/E-stained lungs. Sphingolipid levels in lungs and plasma were measured by tandem liquid chromatography/mass spectrometry. Results: Inspiratory capacity, lung compliance, and body weight all decreased in Ang2-mice (by 13-14%, p<0.05 each) compared to sham. Lung pressure-volume loops exhibited a right-shift in Ang2- vs. sham or untreated mice. There was no significant change in BALF albumin, IgM, or inflammatory cells, or in lung histology inflammation or fibrosis scores in Ang2-mice. Compared to sham, S1P levels were significantly increased in plasma and unlavaged lung in Ang2-mice, decreasing ceramide/S1P ratios (from 3.1 to 2.0, and 26 to 20, respectively, p<0.05 each). Conclusions: Sustained subacute systemic elevations of Ang2 increased lung stiffness, but did not cause severe ALI in mice. Lung and circulatory elevations of S1P but not ceramide may have protected against lung edema and inflammatory injury. Although the cause of increased lung stiffness in this model remains to be elucidated, it is notable that chronic (months) supraphysiological elevations of either Ang2 or S1P have been associated with lung fibrosis. In conclusion, a second-hit injury may be necessary to augment the susceptibility of murine lung to Ang2-induced endothelial damage and inflammation relevant to coronavirus.

11.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927890

ABSTRACT

Rationale. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the third leading cause of death in the United States. While many risk factors for severe COVID-19 are emerging, the effects by which other inhalational exposures affect susceptibility are not well defined. Patients with COVID-19 demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV). When infected with IAV, human small airway epithelial cells (SAEC) exhibit increased abundance of angiotensin-converting enzyme 2 (ACE2), the primary receptor for SARS-CoV-2. However, it remains unknown if this effect increases the risk for COVID-19. Similarly, there are conflicting reports of the effect of e-cigarette (E-cig) vaping on COVID-19 manifestations. We hypothesized that exposures to IAV or E-cig increase the severity of SARS-CoV-2 infection. Methods. Golden Syrian hamsters (male and female) were exposed to E-cig vapor via nebulization for 5d. IAV was administered intranasally once on day 6 (A/California/07/2009 H1N1, 106 PFU/hamster). On day 3 post-IAV infection, SARSCoV- 2 was administered intranasally (WA01;104 PFU/hamster). On day 7 post-SARS-CoV-2 infection animals were sacrificed, bronchoalveolar lavage fluid (BALF) cell differentials were obtained, and inflated lung sections were stained and scored for immunohistology. Lung RNA was quantified for ACE2, TMPRSS2, STAT1, CXCL10, IFN-gamma, gene expression using RT-qPCR. Results: SARS-CoV-2 infection caused progressive weight loss that was less pronounced in animals pre-infected with IAV. SARS-CoV-2 titers from nasal swabs peaked at day 2 in both groups. IAV pre-infection reduced PMN and eosinophils in the BALF, and the overall inflammatory cell infiltration in the lung parenchyma of SARS-CoV-2-infected animals. IAV pre-infection reduced lung levels of STAT1, CXCL10 (2.5-fold;p<0.01), CCL5, and IFN-gamma in SARS-CoV-2-infected animals compared to animals that were only infected with SARS-CoV-2. Pre-exposure to E-cig worsened the SARS-CoV-2-induced weight loss in female animals only. E-cig pre-exposure increased lymphocytes and decreased PMN and eosinophils in the BALF compared to animals that were only infected with SARS-CoV-2. E-cig pre-exposure increased lung levels of STAT1, CXCL10 (2.5-fold;p<0.05), CCL5, and IFN-gamma in SARS-CoV-2-infected animals compared to animals that were only infected with SARS-CoV-2. Conclusion: Pre-infection with IAV resulted in decreased inflammatory response to SARS-CoV-2 infection. In contrast, pre-exposure to E-cig vaping increased the severity of the inflammatory response to SARS-CoV-2 with notable differences between sexes. Whereas anti-viral priming effects of prior viral infection are well described, the mechanisms that explain the worsening effects of E-cig on SARS-CoV-2 outcomes remain unknown.

12.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927853

ABSTRACT

Introduction:Immunocompromised individuals, such as those with HIV and low CD4 counts, are at increased risk for opportunistic infections. Although uncommon, these patients can be infected with multiple organisms, making diagnosis and management challenging for clinicians. Mortality remains high, as the data on initiating and adjusting antimicrobials when there is concern for co-infection is lacking. We present a case of Pneumocystis jiroveci (PCP) and cytomegalovirus (CMV) coinfection resulting in severe hypoxic respiratory failure and death. Case Report:A 38-year-old male with no past medical history presented with fever, dyspnea, and nonproductive cough. Vital signs were notable for a fever of 102.3°F, respiratory rate of 24, and oxygen saturation of 77% on room air. Physical examination revealed an ill-appearing male with bilateral rhonchi who became dyspneic with minimal conversation. Laboratory studies were significant for an elevated c-reactive protein, erythrocyte sedimentation rate, ferritin and lactate dehydrogenase. CT chest demonstrated bilateral ground glass opacities with multifocal consolidations. The patient was admitted for hypoxic respiratory failure secondary to suspected COVID pneumonia, despite negative testing. By hospital day 4, the patient had shown little improvement. Further work-up revealed that he was HIV positive with a CD4 count of 5, so he was empirically started on oral trimethoprim-sulfamethoxazole (TMPSMX) for presumed PCP pneumonia. On hospital day 9, the patient underwent endotracheal intubation for worsening hypoxia and subsequent bronchoscopy for further evaluation. PCP PCR confirmed the diagnosis, and the patient was transitioned to intravenous TMP-SMX. Still with minimal improvement, micafungin was added as potential salvage therapy. After 12 days of TMPSMX, treatment was changed to clindamycin/primaquine. CMV PCR from the bronchoalveolar lavage fluid came back positive at this time, so ganciclovir was added to the regimen. Despite multiple antimicrobials, the patient continued to decline. He was deemed not to be a candidate for ECMO given his profoundly immunocompromised status and ultimately died. Discussion:This case highlights the difficulties clinicians have in managing severely immunocompromised patients who worsen despite appropriate care. Little data exists providing guidelines on when to change to second and/or third-line agents in treating PCP pneumonia. Additionally, further studies need to be completed to delineate in whom empiric antimicrobials should be initiated early when co-infection is a possibility. ECMO may serve a purpose in this patient population given that lung rest is necessary to allow healing, but only a few cases of its use exist at this time.

13.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927787

ABSTRACT

Introduction: Pulmonary Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor;with approximately 248 cases of reported in the literature, making diagnosis and management challenging. Case: A 57-year-old female with past history of hypertension, hyperthyroidism and scoliosis was admitted with worsening chronic right flank pain. Initial lab workup was unremarkable. revealed COVID-19 PCR test was negative. CT chest revealed bilateral pleural effusions and CT abdomen showed 2.8 x2.0cm vague hypo-attenuating lesion in the right hepatic lobe. A repeat CT scan following thoracentesis demonstrated multiple bilateral pulmonary nodules, with the largest located in the right lower lobe (RLL) measuring 2.1cm (Image). Flowcytometry on bronchoalveolar lavage fluid was significant for a CD4/CD8 ratio of 5;however, the transbronchial biopsy was unremarkable. Differential diagnosis included sarcoidosis and hence patient was discharged on prednisone with Bactrim prophylaxis. She underwent VATS lung biopsy. RLL and pleural biopsies revealed EHE. Following the prednisone taper, patient was placed on pazopanib 800mg. The dose of medication subsequently reduced to 300-600mg due to adverse events. Repeat CT scans at 3 months demonstrated minimal change in size of the nodules. Patient continues to be followed on regular basis with a stable clinical status. Discussion: EHE is a low-intermediate grade malignancy which affects mostly liver, lungs and bones;although it can be found in any bodily tissue. Up to 50- 76% of patients are asymptomatic at diagnosis, with the most common symptomatic being local pain. Radiologically, Pulmonary EHE consists of bilateral perivascular nodularity. Our case describes the clinical course of a rare and poorly understood disease. Clinicians must be aware of the characteristics of unusual diseases and pursue robust diagnostic approach. In our case, biopsy led to the definitive diagnosis of EHE. Because of its rarity, there is no standard therapy for metastatic disease. Pazopanib has demonstrated prolonged long-term disease control in observational studies. Some other reports have shown response to cytotoxic chemotherapy such as doxorubicin-containing regimens, however, long-term survival is compromised. Lenalidomide, sorafenib and sunitinib have also been used, but the experience is limited. Our patient is currently on her 4th month of treatment with pazopanib, with 3-month follow-up showing no progression of disease. (Figure Presented).

14.
Topics in Antiviral Medicine ; 30(1 SUPPL):8, 2022.
Article in English | EMBASE | ID: covidwho-1880343

ABSTRACT

Background: Systemic and local inflammation following SARS-CoV-2 infection has been widely described and predictive of disease severity and death. However, the exact immune mediators driving inflammation contributing to SARS-CoV-2 host defense vs. those driving immune-mediated pathology in humans have not been fully elucidated. Deficiencies in type-I interferon (IFN-I) responses, including inborn errors to genes in the IFN-I pathway, neutralizing auto-antibodies against all subtypes of IFN-I, or the lack of production of IFN-I, are associated with severe COVID-19 in otherwise healthy individuals. Conversely, sustained IFN-I responses have been shown to contribute to severe COVID-19 by exacerbating inflammation, and prolonged IFN-I signaling has been shown to interfere with lung repair following viral infection and to increase susceptibility to bacterial infections. Thus, it is critical to understand the roles of IFN-I signaling in COVID-19 to design therapeutic strategies. Methods: Here, we modulated IFN-I signaling in rhesus macaques (Macaca mulatta;RMs) from day-1 through day 2 post SARS-CoV-2 infection (dpi) using an IFN-I antagonist (IFNant). Eighteen RMs (9 control and 9 IFNant treated) were infected with SARS-CoV-2 on day 0, with 6 RMs sacrificed at 2, 4, and 7dpi. Nasal and throat swabs were collected for viral load;blood and bronchoalveolar lavage fluid (BAL) for flow cytometry and RNAseq. Results: IFNant treatment prior to infection resulted in a highly significant and consistent reduction in SARS-CoV-2 viral load in the lower airways (>3-log difference;2dpi BAL) and upper airways (nasal and throat swabs). Treatment with IFNant initiated also potently reduced: (i) soluble markers of inflammation in BAL, (ii) expansion of inflammatory monocytes (CD14+CD16+), and (iii) pathogenesis in the lung. Furthermore, Siglec-1 expression, which has been shown to enhance SARS-CoV-2 infection, was rapidly downregulated in the lung and in monocytes of IFNant-treated RMs. Remarkably, RNAseq analysis showed a robust reduction in pathways associated with inflammation and decreased levels of interferon-stimulated genes post-infection in treated RMs. Thus, IFNant treatment prior to infection resulted in limited viral replication, inflammation, and pathogenesis in SARS-CoV-2-infected RMs. Conclusion: These data indicate a vital, early role of IFN-I in regulating COVID-19 progression and emphasize the importance of understanding IFN-I pathways in COVID-19 for the development of targeted therapeutic strategies.

15.
J Infect Dis ; 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1873928

ABSTRACT

The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (DXM+ or DXM-) and 8 non-COVID-19 critically ill controls. CARDS (+DXM) was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Most ISGs were upregulated in CARDS, particularly in CARDS (-DXM). In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other local immune responses.

16.
J Clin Med ; 11(8)2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1809954

ABSTRACT

The study objective was to evaluate chest radiographic features that distinguish Mycoplasma pneumoniae pneumonia (MPP) from other bacterial pneumonias diagnosed based on the bacterial floral analysis with 16S rRNA gene sequencing, using bronchoalveolar lavage fluid samples directly obtained from pneumonia lesions. Patients were grouped according to the dominant bacterial phenotype; among 120 enrolled patients with CAP, chest CT findings were evaluated in 55 patients diagnosed with a mono-bacterial infection (one bacterial phylotype occupies more than 80% of all phylotypes in a sample) by three authorized respiratory physicians. Among this relatively small sample size of 55 patients with CAP, 10 had MPP, and 45 had other bacterial pneumonia and were categorized into four groups according to their predominant bacterial phylotypes. We created a new scoring system to discriminate MPP from other pneumonias, using a combination of significant CT findings that were observed in the M. pneumoniae group, and age (<60 years) (MPP-CTA scoring system). When the cutoff value was set to 1, this scoring system had a sensitivity of 80%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 95%. Among the CT findings, centrilobular nodules were characteristic findings in patients with MPP, and a combination of chest CT findings and age might distinguish MPP from other bacterial pneumonias.

17.
International Journal of Pharmaceutical and Clinical Research ; 14(2):314-319, 2022.
Article in English | EMBASE | ID: covidwho-1777144

ABSTRACT

Aim: The aim of the present study to determine the emerging cases of mucormycosis in post Covid-19 disease patients. Materials and Methods: This observational study was carried out in the Department of Microbiology, Patna Medical College, Patna, Bihar, India for 1 year. Basic microbiological methods such as gram stain and KOH smear were used for the detection of MC in the received clinical specimen and morphology was seen in the microscope. Results: During study period our microbiology lab received n=30 suspected clinical specimens from N= 20 post covid-19 patients for MC diagnosis over one month period. Out of n=30 specimens, n=5 was positive for MC by gram and KOH smear method, and we saw filamentous fungi by conventional microscopic method. Conclusions: The present study concluded that the cases of life-threatening MC increase day by day in central India as post complication of covid-19 disease.

18.
J Virol ; 96(6): e0187321, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1759293

ABSTRACT

Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, the immunopathogenic events occurring with coinfections of SARS-CoV-2 and IAV remain unclear. Here, we report the pathogenic and immunological consequences of SARS-CoV-2 and IAV H1N1 coinfection in the K18-hACE2 transgenic mouse model. Compared with a single infection with SARS-CoV-2 or IAV, coinfections not only prolonged the primary virus infection period but also increased immune cell infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid leading to severe pneumonia and lung damage. Moreover, coinfections caused severe lymphopenia in peripheral blood, resulting in reduced total IgG, neutralizing antibody titers, and CD4+ T cell responses against each virus. This study sheds light on the immunopathogenesis of SARS-CoV-2 and IAV coinfection, which may guide the development of effective therapeutic strategies for the treatment of patients coinfected with these viruses. IMPORTANCE The cocirculation of influenza virus merging with the COVID-19 pandemic raises a potentially severe threat to public health. Recently, increasing numbers of SARS-CoV-2 and influenza virus coinfection have been reported from many countries. It is a worrisome issue that SARS-CoV-2 coinfection with other pathogens may worsen the clinical outcome and severity of COVID-19 and increase fatality. Here, we evaluated SARS-CoV-2 and IAV coinfection using the K18-hACE2 mouse model. Coinfected mice exhibited increased mortality with prolonged IAV shedding. Furthermore, coinfected mice showed a higher level of cytokines and chemokines than a single infection condition. Interestingly, our data show that coinfected mice showed significantly fewer virus-specific and neutralizing antibodies than the mice with a single infection. Overall, this study suggests that coinfection aggravates viral pathology by impaired neutralizing antibody response.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Orthomyxoviridae Infections , SARS-CoV-2 , Animals , Antibodies, Neutralizing , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Coinfection/immunology , Disease Models, Animal , Humans , Influenza A Virus, H1N1 Subtype/immunology , Mice , Orthomyxoviridae Infections/immunology , SARS-CoV-2/immunology , Severity of Illness Index
19.
Cocuk Enfeksiyon Dergisi ; 15(4):236-239, 2021.
Article in Turkish | EMBASE | ID: covidwho-1650975

ABSTRACT

Objective: With the rapid spread of SARS-CoV-2, a new coronavirus, around the world, a pandemic was declared by World Health Organization on March 2020. The first cases were reported in March 2020 from Turkey. In our hospital, the first pediatric case was detected on April 2, 2020. However, there is no data on whether this virus had been present in our region or not before this date. The aim of our study was to de-termine the first entry of SARS-CoV-2 virus to our region for pediatric patients. Material and Methods: SARS-CoV-2 positivity was investigated retro-spectively with the RT-qPCR method in the pediatric respiratory tract specimens taken between the October 1, 2019 and March 31, 2020. In the specimens, SARS-CoV-2 RNA was studied using real-time PCR based “COVID-19 RT-qPCR Detection Kit”. Results: 886 samples were included in the study. Of the respiratory tract specimens, 97.1% were nasopharyngeal swabs, 2.8% were bronchoal-veolar lavage. Most frequently, rhinovirus (28.6%), influenza A subtype H1N1 (pandemic H1N1) (18.5%) and influenza B (16%) were detected. Rhinovirus and enterovirus were the most frequent double agents seen together. No SARS-CoV-2 positivity was detected in the respiratory tract specimens studied. Conclusion: SARS-CoV-2 PCR test was conducted in a limited number of centers at the beginning of the pandemics may have affected the detection of the first case in Turkey. Multicenter studies of archived samples would enable more realistic results in tracking SARS-CoV-2 in our country.

20.
Chest ; 161(1):A371, 2022.
Article in English | EMBASE | ID: covidwho-1636218

ABSTRACT

TYPE: Case Report TOPIC: Occupational and Environmental Lung Diseases INTRODUCTION: We present a case of exogenous lipoid pneumonia caused by paraffin broncoaspiration due to pharyngoesophageal motor dysphagia. CASE PRESENTATION: A 57 year old female consulted for diarrhea. She had a previous history of ischemic stroke related to hypercoagulability syndrome, causing oropharyngeal dysphagia due to pharyngo-esophageal motor incoordination. Owing to possible neurogenic dysfunction she also presented megadolichocolon with chronic diarrhea-constipation syndrome. Due to the epidemiological situation caused by SARS-COV2, a chest X-ray was performed showing increased density of the right middle lobe. The control X-ray exhibited a persistence of this alteration, therefore a thoracic tomographic study was performed (findings included in image), as well as a bronchoalveolar lavage. The bronchoalveolar lavage fluid was initially turbid white which, posterior to resting, revealed a superficial layer of fat, supporting the diagnosis of lipoid pneumonia. The patient was subsequently interrogated. She associated the consumption of oily materials from herbalists and paraffin in order to palliate her constipation symptoms, which in relation to her esophageal motor-pharyngeal incoordination produced bronchoaspiration of the referred oily material. DISCUSSION: Oily substance ingestion was suspended. Subsequently she underwent a corticosteroid treatment and is currently under clinical control. CONCLUSIONS: The ground glass pattern is a finding that causes a wide differential diagnosis in the radiological study, therefore it is of great importance to take an adequate clinical history and to take into account the motor dysfunctions related to swallowing, due to the high consumption of herbalist products that contain oily materials that can cause exogenous lipoid pneumonia. DISCLOSURE: Nothing to declare. KEYWORD: Exogenous_Lipoid_Pneumonia

SELECTION OF CITATIONS
SEARCH DETAIL