COVID-19 Impairs Immune Response to Candida albicans

Abstract

Infection with SARS-CoV-2 can lead to Coronavirus disease-2019 (COVID-19) and result in severe acute respiratory distress syndrome (ARDS). Recent reports indicate an increased rate of fungal coinfections during COVID-19. With incomplete understanding of the pathogenesis and without any causative therapy available, secondary infections may be detrimental to the prognosis. We monitored 11 COVID-19 patients with ARDS for their immune phenotype, plasma cytokines, and clinical parameters on the day of ICU admission and on day 4 and day 7 of their ICU stay. Whole blood stimulation assays with lipopolysaccharide (LPS), heat-killed <i>Listeria monocytogenes</i> (HKLM), <i>Aspergillus fumigatus</i>, and <i>Candida albicans</i> were used to mimic secondary infections, and changes in immune phenotype and cytokine release were assessed. COVID-19 patients displayed an immune phenotype characterized by increased HLA-DR⁺CD38⁺ and PD-1⁺ CD4⁺ and CD8⁺ T cells, and elevated CD8⁺CD244⁺ lymphocytes, compared to healthy controls. Monocyte activation markers and cytokines IL-6, IL-8, TNF, IL-10, and sIL2R<i>α</i> were elevated, corresponding to monocyte activation syndrome, while IL-1β levels were low. LPS, HKLM and <i>Aspergillus fumigatus</i> antigen stimulation provoked an immune response that did not differ between COVID-19 patients and healthy controls, while COVID-19 patients showed an attenuated monocyte CD80 upregulation and abrogated release of IL-6, TNF, IL-1α, and IL-1β toward <i>Candida albicans</i>. This study adds further detail to the characterization of the immune response in critically ill COVID-19 patients and hints at an increased susceptibility for <i>Candida albicans</i> infection.