key: cord-0891776-4gvyykb3
authors: Maldonado, Ivana; Elisiri, María Elisa; Fernández-Canigia, Liliana; Sánchez, Ana Victoria; López, Liana; Toranzo, Adriana I; López-Joffre, Cecilia; González-Fraga, Sol; Canteros, Cristina Elena
title: COVID-19 asociado a histoplasmosis diseminada en un paciente trasplantado renal
date: 2021-12-18
journal: Rev Argent Microbiol
DOI: 10.1016/j.ram.2021.10.006
sha: ef16c40d391994042fcd12e6eb5a1b6e5035e80c
doc_id: 891776
cord_uid: 4gvyykb3

We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS- CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient’s progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis. Se presenta un caso de histoplasmosis diseminada e infección por COVID-19 en un paciente trasplantado renal en Argentina. El paciente presentó un cuadro clínico respiratorio y la tomografía computarizada (TC) de tórax mostró múltiples opacidades centrolobulillares bilaterales con patrón de árbol en brote. El paciente fue tratado inicialmente con antibióticos para agentes causantes de neumonía bacteriana adquirida en la comunidad y luego como tuberculosis. Un mes después se le diagnosticó una histoplasmosis diseminada y el hongo fue aislado de esputo, piel y mucosa oral. El hongo fue tipificado molecularmente como Histoplasma capsulatum clado LAmB. El paciente fue hospitalizado y se inició tratamiento con anfotericina B liposomal vía intravenosa. Durante el transcurso de la terapia antifúngica los síntomas respiratorios del paciente empeoraron, una nueva TC de tórax mostró una lesión unilateral con apariencia de vidrio esmerilado y se detectó SARS-CoV-2 en el hisopado nasofaríngeo. El paciente fue tratado con plasmoterapia y se modificó el régimen de inmunosupresión (se interrumpió everolimus, se redujo micofenolato de mofetilo y se incrementó la meprednisona). La evolución del paciente fue favorable y fue dada de alta con tratamiento oral con itraconazol.

Se presenta un caso de histoplasmosis diseminada e infección por COVID-19 en un paciente trasplantado renal en Argentina. El paciente presentó un cuadro clínico respiratorio y la tomografía computarizada (TC) de tórax mostró múltiples opacidades centrolobulillares bilaterales con patrón de árbol en brote. El paciente fue tratado inicialmente con antibióticos para agentes causantes de neumonía bacteriana adquirida en la comunidad y luego como tuberculosis. Un mes después se le diagnosticó una histoplasmosis diseminada y el hongo fue aislado de esputo, piel y mucosa oral. El hongo fue tipificado molecularmente como Histoplasma capsulatum clado LAmB. El paciente fue hospitalizado y se inició tratamiento con anfotericina B liposomal vía intravenosa. Durante el transcurso de la terapia antifúngica los síntomas respiratorios del paciente empeoraron, una nueva TC de tórax mostró una lesión unilateral con apariencia de vidrio esmerilado y se detectó SARS-CoV-2 en el hisopado nasofaríngeo. El paciente fue tratado con plasmoterapia y se modificó el régimen de inmunosupresión (se interrumpió everolimus, se redujo micofenolato de Page 4 of 16 J o u r n a l P r e -p r o o f 4 mofetilo y se incrementó la meprednisona). La evolución del paciente fue favorable y fue dada de alta con tratamiento oral con itraconazol. In addition, FFPE tissue specimens were analyzed using both PCRs, a nested conventional PCR that amplified a fragment of the HP100 gene and a real time quantitative PCR that amplified the ITS1 fragment 4 During his hospital stay, on June 16, due to a worsening of the symptoms, and chest CT findings (Fig. 2c) , a new nasopharyngeal swab sample for SARS-CoV-2 detection was performed in the context of the COVID-19 pandemic, and viral RNA was detected.

The patient's immunosuppressive regimen was changed, everolimus was discontinued, mycophenolate mofetil was reduced and meprednisone was increased. On July 4, the patient was discharged with favorable evolution, and SARS-CoV-2 RNA was detected in a nasopharyngeal swab sample until July 24. Histoplasmosis has often resulted in allograft loss and overall mortality 6 . Moreover, COVID-19 co-infection may be severe, requiring intensive care admission of kidney transplant recipients due to long-term immunosuppression 12 . In the case reported here, the patient had a favorable outcome probably because histoplasmosis was rapidly diagnosed and treated. In addition, he was treated early, after the diagnosis of SARS-CoV-2, with convalescent plasma therapy in line with the management of COVID-19 in kidney transplant recipients published by some authors 11 .

The molecular analysis of four genes using MLST identified the isolate as belonging to the LAmB clade, which did not surprise us since this clade is the predominant one in South America and the major clade circulating in Argentina 7 .

Twenty days after the last discharge, SARS-CoV-2 RNA was detected in a nasopharyngeal swab sample. This coincides with some authors who noted that in immunosuppressed renal transplant recipients SARS-CoV-2 viral shedding could be prolonged 15 . In the context of the COVID-19 pandemic it is important to pay attention to endemic mycoses such as histoplasmosis, since they exhibit respiratory symptoms that can be mistaken with viral or bacterial community-acquired pneumonia, and in pulmonary and disseminated histoplasmosis they can resemble other infections such as tuberculosis.

To the best of our knowledge, this is the first report in the medical literature of COVID-19 associated with disseminated histoplasmosis in a renal transplant recipient. COVID-19 disease should be considered in patients with histoplasmosis, as well as other endemic mycoses and prolonged immunosuppression, particularly during the pandemic. a. Multiple bilateral centrilobular opacities, with tree-in-bud pattern during first hospitalization.

b. Slight increase of multiple bilateral centrilobular opacities during second hospitalization.

c. Follow-up CT image obtained 10 days later of the third hospitalization shows multifocal peripheral abnormalities (circle) with ground glass pattern involve right lung. 

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Histoplasmosis after solid organ transplant

COVID-19-Associated Histoplasmosis in an AIDS Patient

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Typical and atypical COVID-19 computed tomography findings

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Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV-A Case Report from Argentina and Literature Review

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The feared five fungal infections in kidney transplant recipients: A single-center 20-year experience

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Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China