Discussion
The possibility of SARS-CoV-2 co-infections with bacterial, fungal and also viral pathogens should not be neglected. Fungal co-infections among hospitalized patients with COVID-19 is a challenging issue. Few recent studies revealed cases of COVID-19 infection involving more than one species of aspergillus or concomitant two different fungal infections. Costache et al. reported a case of COVID-19 associated pulmonary aspergillosis with both Aspergillus fumigatus andAspergillus flavus with favorable outcome [2]. Johnson et al. reported a case of combined probable pulmonary aspergillosis and possible mucormycosis in a diabetic male with COVID-19 in the ICU who treated with liposomal amphotericin B [3].
Critical illness is an important risk factor for CMV reactivation due to immunosuppression. Although co-infections with CMV are frequent in the critically ill patients, but the impact on COVID-19 patients is unclear. Moniz et al. presented five case reports of CMV reactivation in COVID-19 patients admitted to the ICU with respiratory failure [4]. It has been well described that critical or severe illness can induce immune suppression. The most common laboratory finding in patients with COVID-19 is lymphopenia, which correlate to diseases severity. Recent findings revealed that disease severity is dominated by the decline in cell-mediated immunity especially the decrease in T cell counts [5]. On the other hand, number of iatrogenic factors including the usage of corticosteroids in the treatment of severe COVID-19 may predispose the patients to other infection [6]. In addition to ICU admission and mechanical ventilation, other entities including transfusions, sepsis, corticosteroids and acute respiratory distress syndrome have also been found to be associated with the risk of CMV reactivation [7].
In a minority of patients, bacterial and fungal co-infections can complicate the course of COVID-19 infection. In a retrospective study, the second most common respiratory pathogen detected from patients with COVID-19 was Klebsiella pneumoniae [8, 9]. Montrucchio et al. reported patients with COVID-19 related acute respiratory distress syndrome who developed invasive infections due to carbapenemase-producing Klebsiella pneumoniae [10]. In our patient, the culture of empyema and visceral pleural peel, confirmed the superimposed of Klebsiella pneumoniae infection on COVID-19.
Tissue invasion by a filamentous fungus through histopathological examination of biopsy, provides a diagnosis of proven invasive fungal infections and positive culture of Aspergillus from the specimen is required to make a proven diagnosis of invasive aspergillosis [11]. In our case, right upper lobe wedge resection and right lower lobe wedge resection revealed wide and irregular fungal hyphae indicative of mucormycosis. Also vessel wall infiltrated by several thin and also broad fungal hyphae. Calcium oxalate crystals accompanied by fungal hyphae was indicative of aspergillosis. Definitive diagnosis of CMV pneumonia is determined based on lung tissue samples by histopathologic testing and immunohistochemical analysis [12]. According to the data, our case is consistent with the proven CMV pneumonia.
According to the histopathology and IHC, our patient had pulmonary aspergillosis, mucormycosis, and CMV disease with Klebsiella pneumoniae infection. The combined risk factors including diabetes mellitus, recent corticosteroid treatment and also COVID-19 per se, contributed to concomitant infections in our patient which is a unique report.