Fungal Infections in Critically Ill COVID-19 Patients: Inevitabile Malum

Abstract

Patients with severe COVID-19 belong to a population at high risk of invasive fungal infections (IFIs), with a reported incidence of IFIs in critically ill COVID-19 patients ranging between 5% and 26.7%. Common factors in these patients, such as multiple organ failure, immunomodulating/immunocompromising treatments, the longer time on mechanical ventilation, renal replacement therapy or extracorporeal membrane oxygenation, make them vulnerable candidates for fungal infections. In addition to that, SARS-CoV2 itself is associated with significant dysfunction in the patient's immune system involving both innate and acquired immunity, with reduction in both CD4⁺ T and CD8⁺ T lymphocyte counts and cytokine storm. The emerging question is whether SARS-CoV-2 inherently predisposes critically ill patients to fungal infections or the immunosuppressive therapy constitutes the igniting factor for invasive mycoses. To approach the dilemma, one must consider the unique pathogenicity of SARS-CoV-2 with the deranged immune response it provokes, review the well-known effects of immunosuppressants and finally refer to current literature to probe possible causal relationships, synergistic effects or independent risk factors. In this review, we aimed to identify the prevalence, risk factors and mortality associated with IFIs in mechanically ventilated patients with COVID-19.

Keywords: CAC; CAM; CAPA; COVID-19; critically ill; fungal infections.

Figure 1

SARS-CoV2 spike protein binds to angiotensin converting enzyme 2 (ACE2) receptor of epithelial cells and type 2 pneumocytes, thus allowing viral entry. The release of danger-associated molecular patterns (DAMPs) by dying or damaged cells ignites an immune response and a cascade of inflammation, which in turn leads to tissue damage. This extensive lung damage may lead to higher vulnerability to invasive fungal infections.