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 Listeria monocytogenes (HKLM), Aspergillus fumigatus , and Candida albicans 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 α were elevated, corresponding to monocyte activation syndrome, while IL-1β levels were low. LPS, HKLM and Aspergillus fumigatus 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 Candida albicans . 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 Candida albicans infection.
【저자키워드】 SARS-CoV-2, acute respiratory distress syndrome, second hit, lipopolysaccharide, yeast, fungal, Listeria monocytogenes, 【초록키워드】 COVID-19, coronavirus disease, ARDS, coronavirus, immune response, therapy, Cytokines, Pathogenesis, Lymphocytes, acute respiratory distress syndrome, Prognosis, T cells, IL-6, susceptibility, Infection, cytokine, CD4, CD8, ICU, Antigen, coronavirus disease-2019, monocyte, PD-1, Secondary infection, Critically ill, ICU admission, IL-8, plasma, IL-10, HLA-DR, CD38, secondary infections, lipopolysaccharide, COVID-19 patients, Blood, Aspergillus fumigatus, acute respiratory distress, LPS, TNF, Clinical parameters, marker, IL-1β, Candida albicans, Listeria monocytogenes, detrimental, COVID-19 patient, critically ill COVID-19 patients, respiratory distress, characterization, Immune phenotype, Activation, severe acute respiratory distress syndrome, Monocyte activation, syndrome, upregulation, healthy controls, cytokine release, IL-1α, cytokines IL-6, CD80, clinical parameter, CD244, recent, not differ, elevated, characterized, were used, changes in, abrogated, Candida albican, Listeria monocytogene, were assessed, 【제목키워드】 COVID-19, response, Candida,