Susceptibility from the immunological perspective of COVID-19-associated pulmonary aspergillosis: A literature review

Abstract

The incidence rate of COVID-19-associated pulmonary aspergillosis (CAPA) is rising. However, the pathogenesis of CAPA remains unclear. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection disrupts pathways related to type I interferon and Toll-like receptors, key components in innate immunity, thereby elevating the incidence of CAPA. Additionally, SARS-CoV-2 infection results in T and B cell functional deficiencies or exhaustion within adaptive immunity, weakening the defense against invasive Aspergillus. Furthermore, SARS-CoV-2 infection enhances the replication of cytomegalovirus and alters the gut microbiota, factors that may aid in diagnosing CAPA. Immunosuppressive therapy in COVID-19 patients is also believed to heighten the risk of invasive aspergillosis. Therefore, this review, examines the immune response to SARS-CoV-2 infection combined with invasive aspergillosis, and explores the pathogenesis and susceptibility factors of CAPA. We propose that variations in an individual's immune response significantly determine susceptibility to CAPA. The aim of this paper is to deepen clinical understanding of CAPA's pathogenesis, thereby aiding in mitigating susceptibility risk and advancing novel treatment approaches.

Keywords: CAPA; COVID-19 drug treatment; COVID-19-associated pulmonary aspergillosis; SARS-CoV-2; immuneresponse.

Figure 1.

(A) After SARS-CoV-2 infection, respiratory epithelial cells are destroyed. (B) Invasive Aspergillus infection is facilitated by damaged respiratory epithelial cells. (C) SARS-CoV-2 inhibits type I and III interferons required for fungal immunity. (D) SARS-CoV-2 decreases antifungal immunity by inhibiting the activity of alveolar macrophages and neutrophils. (E) Patients with severe COVID-19 may have increased immune system activation, which can cause cytokine storms and weaken their immunological defenses against invasive Aspergillus infection. COVID-19 = Corona Virus Disease 2019, SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2.

Figure 2.

(A) During SARS-CoV-2 infection, lung epithelial cells are continuously destroyed, and Aspergillus invasion with spores releases molecules that may promote membrane permeability and tissue damage, which again destroys lung epithelial cells. (B) The SARS-CoV-2 virus inhibits Th1 via CD4+ T cells. (C) Th1 secretes cytokine IFN-γ. (D) Th2 secretion of IL-10 is increased in COVID-19 patients, and increased IL-10 increases the risk of invasive Aspergillus infections. (E) SARS-CoV-2 infection increased the expression of PD-1, and invasive Aspergillus infection increased the expression of PD-L1. The interaction between PD-1 and PD-L1 promoted Treg cell response and inhibited Th1 response. SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2.