key: cord-0765181-512ab587
authors: Sasoni, Natalia; Müller, Milton Rodriguez; Posse, Graciela; González, Jorge; Leonardelli, Florencia; Garcia-Effron, Guillermo
title: SARS-CoV-2 and Aspergillus section Fumigati coinfection in an immunocompetent patient treated with corticosteroids
date: 2020-11-28
journal: Rev Iberoam Micol
DOI: 10.1016/j.riam.2020.11.001
sha: 9bcdf3946e393487293e07775b4125b88d532775
doc_id: 765181
cord_uid: 512ab587

Background: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. Case report: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. Conclusions: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.

J o u r n a l P r e -p r o o f described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis.

Case report: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment.

Conclusions: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.

Page 3 of 10 J o u r n a l P r e -p r o o f Antecedentes: Los pacientes con neumonía viral grave reciben altas dosis de fármacos inmunomoduladores para prevenir el empeoramiento clínico. Los pacientes con influenza grave que reciben esteroides tienen neumonías secundarias causadas por Aspergillus con una frecuencia relativamente alta. Los pacientes con COVID-19 ingresados en la Unidad de Cuidados Intensivos (UCI) reciben dicha medicación como parte de su tratamiento y comparten con otro tipo de pacientes muchas de las características clínicas de otras neumonías virales graves. Estos pacientes deberían considerarse como un grupo de riesgo de aspergilosis invasiva.

Caso clínico: Se presenta un caso de coinfección por SARS-CoV-2 y Aspergillus de la sección Fumigati en un paciente intubado de edad avanzada con antecedentes de embolia pulmonar y tratado con corticosteroides. El diagnóstico siguió las definiciones ad hoc descritas para pacientes ingresados en la UCI con gripe grave. El paciente cumplía varios criterios clínicos (fiebre durante 3 días refractaria al tratamiento antibiótico apropiado, disnea, fricción pleural, empeoramiento del estado respiratorio a pesar del tratamiento antibiótico y la necesidad de soporte respiratorio), el criterio radiológico (infiltrado pulmonar) y un criterio micológico (test de galactomanano positivo en suero, (ratio ≥0.5).

Además, se detectó ADN de Aspergillus de la sección Fumigati en muestras de suero y sangre del paciente. Estas pruebas fueron positivas 4 semanas después de que el paciente ingresara en la UCI. El paciente recibió tratamiento con voriconazol y después de dos meses en la UCI mejoró su estado pulmonar; fue dado de alta después de 6 semanas de tratamiento antifúngico.

Conclusiones: Los pacientes gravemente enfermos con COVID-19 deberían considerarse un nuevo grupo de riesgo para la aspergilosis. La detección de galactomanano y ADN de (4) were performed on the same samples. Those molecular tests were positive in the first three samples (Figure 1 ).

After the first positive galactomannan/PCR assay, 50 mg/day deoxicholate amphotericin-B were administered for three days (it was, along with fluconazole, the only available antifungal agent at the institution). Then, the antifungal treatment was shifted to voriconazole (IV 6 mg/kg/12 h the first day, followed by IV 4 mg/kg/12 h that was shifted to oral voriconazole 200 mg/12 h) and TMS was discontinued. In the meanwhile, the patient was reintubated (orotracheal) and two days later a percutaneous tracheostomy was performed. No mycological cultures were performed before starting the antifungal treatment (the culture was performed with a sample obtained on May 3 rd , when the results of galactomanan and PCR were already negative). On April 30 th the result of SARS-CoV-2 RT-PCR was negative, and the same result was obtained for the second time on May 4 th . On May 10 th , the patient began to breathe without assistance for several hours. Since then, his respiratory status improved markedly, he had no fever and leukocytes count was lower than 11,000 cells/ml. Oral voriconazole treatment for 6 weeks was prescribed. On May 26 th and on June 2 th he was discharged from ICU and from the hospital, respectively. This case accomplishes the ad hoc definitions described for patients admitted to the ICU with severe influenza, including several clinical criteria, and radiological and mycological criteria. In addition, Aspergillus section Fumigati DNA was detected in serum and blood samples, a result that fulfills the EORCT/MSGER definitions for the diagnosis of probable invasive aspergillosis (1). These evidences were obtained one month after the patient´s ICU J o u r n a l P r e -p r o o f admission. After receiving the proper antifungal treatment, patient´s respiratory function improved. As a conclusion we can state that aspergillosis should be considered a probable comorbidity in seriously ill patients with COVID-19 receiving corticosteroids. Furthermore, screening the presence of galactomannan in serum could be carried out routinely in these patients (taking into account, anyway, the known limitations of this technique in nonimmunosuppressed patients), especially considering that COVID-19/Aspergillus coinfection has been recently reported (5, 8) . 

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The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.