Defective antifungal immunity in patients with COVID-19

Abstract

The COVID-19 pandemic has placed a huge strain on global healthcare and been a significant cause of increased morbidity and mortality, particularly in at-risk populations. This disease attacks the respiratory systems and causes significant immune dysregulation in affected patients creating a perfect opportunity for the development of invasive fungal disease (IFD). COVID-19 infection can instill a significant, poorly regulated pro-inflammatory response. Clinically induced immunosuppression or pro-inflammatory damage to mucosa facilitate the development of IFD and Aspergillus, Mucorales, and Candida infections have been regularly reported throughout the COVID-19 pandemic. Corticosteroids and immune modulators are used in the treatment of COVID-19. Corticosteroid use is also a risk factor for IFD, but not the only reason for IFD in COVID -19 patients. Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for IFD. The COVID-19 pandemic has significantly increased the at-risk population for IFD. Even if the incidence of IFD is relatively low, the size of this new at-risk population will result in a substantial increase in the overall, annual number of IFD cases. It is important to understand how and why certain patients with COVID-19 developed increased susceptibility to IFD, as this will improve our understanding of risk of IFD in the face of future pandemics but also in a clinical era of increased clinical immuno-suppression/modulation.

Invasive Pulmonary Aspergillosis After Sars-CoV-2 Infection as Limitation of Contemporary Transplantology: A Case Report

“…Immune system dysregulation is manifested through the functional debilitation of natural killer cells and T cells. This has been detected in COVID-19 patients through decreased levels of its markers, NK-G2A and PD-1 [12] . Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune imbalance is an important risk factor for invasive fungal diseases.…”

Oral Candidiasis in Adult and Pediatric Patients with COVID-19

“…Thus opportunistic Candida infection due to immune hypo reaction may be more common in adults. In addition, other authors have reported that several pathogenic mechanisms occurring during COVID-19, such as immunosuppression and pro-inflammatory cytokines cascade, associated with the reduced fungicidal activity of neutrophils may cause direct damage to the oral mucosa and contribute to streamlining the Candida infections [ 36 ].…”

“…Most cases of Candida infection in COVID-19 patients occur in subjects admitted at the intensive care units (ICUs), meanly after a week from the recovery [ 50 , 51 ], being responsible for a two-fold mortality risk compared to patients with candidemia without COVID-19 [ 36 , 50 , 52 ].…”

Lower Concentrations of Amphotericin B Combined with Ent-Hardwickiic Acid Are Effective against Candida Strains

“…Patients hospitalized with COVID-19 receive immunosuppressive medication that potentially increases the susceptibility of these patients to co-infections, including polymicrobial Candida infections [ 21 , 22 ]. However, according to the literature, this is not the only reason for the increase in invasive fungal infections [ 23 ]. Defective antifungal immunity in patients of COVID-19 due to a dysregulation of the immune system has been observed through the expression of exhaustion markers of natural killer cells and T cells [ 23 ].…”

“…However, according to the literature, this is not the only reason for the increase in invasive fungal infections [ 23 ]. Defective antifungal immunity in patients of COVID-19 due to a dysregulation of the immune system has been observed through the expression of exhaustion markers of natural killer cells and T cells [ 23 ]. In addition, patients with COVID-19 also have reduced fungicidal activity of neutrophils [ 23 ].…”