Severe mold fungal infections in critically ill patients with COVID-19

Abstract

The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.

Keywords: CAM; CAPA; COVID-19; antifungals; aspergillosis; critical illness; molds; mucormycosis.

Figure 1.

COVID-19-associated pulmonary aspergillosis pathogenesis. Invasive pulmonary aspergillosis is an opportunistic infection occurring in vulnerable patients after inhalation of conidia or spores of Aspergillus spp. SARS-CoV-2 pneumonia and ARDS create favorable conditions for Aspergillus growth and tissue invasion, causing epithelial lung damage, create an inflammatory environment, and dysregulating the immune response and clearance of the fungus, while corticosteroids and IL-6 inhibitors, used for severe COVID-19 treatment, also play a role in CAPA development.

Figure 2.

COVID-19-associated aspergillosis diagnosis. CAPA diagnosis is challenging, as non-immunocompromised critically ill patients lack the classical host risk factors. Bronchoscopy with BAL is the most reliable diagnostic tool to obtain lower respiratory tract samples for direct microscopy, cultures, PCR, GM, LFD and discriminate colonization from invasive pulmonary aspergillosis (IPA). Imaging findings of IPA may overlap with those of COVID-19 pneumonia and typical signs, such as the halo and air crescent sign, are not commonly seen in CAPA.

Figure 3.

COVID-19-associated mucormycosis presentation and pathogenesis. The most common form is the rhino-orbital-cerebral, followed by the pulmonary form. SARS-CoV-2 infection enhances Mucor growth and contributes to tissue invasion in multiple ways: causing immune dysregulation and endothelial dysfunction, and creating a hypoxic, acidotic environment.