DISCUSSION
Our report illustrates the importance of considering IPA in patients with underlying severe COVID-19, who show no clear clinical impairment related to IPA throughout their hospitalization. In this case, the patient was likely immunologically compromised due to his underlying conditions (Type II diabetes mellitus and chronic kidney disease). This case underscores the need to investigate this neglected disease and allow for early tracing with antifungal treatment; however, it is necessary to consider the risks posed by the bronchoscopy that must be performed for the diagnosis. Antinori et al. 8  assessed the postmortem lung examination of a patient with IPA and COVID-19, in which IPA was characterized by bronchial wall ulceration associated with multiple spots of necrotizing pneumonia, and the residual lung parenchyma displayed a pattern of acute lung injury with diffuse alveolar damage. In addition to the presence of bronchopneumonia, we distinctly show fungi (hyphae and conidia) within blood vessels, the hallmark of the invasive disease triggered by this fungus. The presence of GM in bronchoalveolar lavage is a useful marker, but this procedure is not performed in many COVID-19 patients for biosafety reasons. However, the identification of this antigen in peripheral blood, a test that is usually negative, is seemingly a reliable marker of invasive disease, especially in our case, in which the invasion of vessels was observed.
In addition, it is important to consider that the use of medications, such as oseltamivir, which is preemptively prescribed for influenza infection, may potentially block host neuraminidase, thus increasing patient susceptibility to IPA 5  ,  6 . The use of corticosteroids, which is still a matter of debate in COVID-19 treatment, may also facilitate invasive disease. Therefore, we recommend caution in the use of corticosteroids and oseltamivir to treat SARS-CoV-2 infection. Meanwhile, chloroquine has been proposed as a drug with antifungal and immune response properties 11 . As the patient clinical status was already critical upon his arrival and he died three days after hospitalization, the possibility of a hospital-acquired fungal infection is unlikely. It is possible that aspergillosis could predispose patients with COVID-19 to clinical worsening, and it is therefore necessary to further assess this two-way interaction between both infections.
A. penicillioides is a xerophilic species occurring in dry habitats and in house dust; it is responsible for human and animal allergies. Dry oxygen supplementation intended to prevent aerosolization could explain the infection caused by this pathogen 12 . To the best of our knowledge, this is the fourth clinical report on A. penicillioides clinical infection. The other three are classified as keratitis, disseminated disease in a child with cystic fibrosis, and central nervous system arteritis 13  ,  14  ,  15 . No information is available on the antifungal sensitivity of this species or the frequency of invasive disease.
In conclusion, we report a case of IPA in a patient with severe pneumonia associated with COVID-19. Using a gold standard method (histopathology) in our case series, the frequency of IPA was lower, as compared to that of cases published elsewhere; possible overestimation might be due to contamination. In our case, no CT imaging of the lung, sequential GM, or culture for fungus was performed, thus reinforcing the role of autopsies as a form of postmortem surveillance of such a severe disease. As the outbreak of COVID-19 continues to spread around the world, further reports are needed to assess the occurrence and frequency of IPA in severe SARS-CoV-2 infections, and their clinical interaction. These studies are needed to assess the incidence of IPA and define at-risk populations, thus offering a strategy for diagnosis, prophylaxis, and timely clinical management.