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 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 sIL2Rα 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.
Highlights
The novel coronavirus 2019-nCov, named SARS-CoV-2, has rapidly spread around the globe since its discovery in Wuhan, China, in December 2019
Between April and May 2020, 11 COVID-19 patients with acute respiratory distress syndrome (ARDS) were included in this study
We provide detailed analyses of the immune state of critically ill COVID-19 patients during their intensive care unit (ICU) stay and compare them to healthy controls
Summary
The novel coronavirus 2019-nCov, named SARS-CoV-2, has rapidly spread around the globe since its discovery in Wuhan, China, in December 2019. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19), where respiratory symptoms may include cough, breathing difficulties, and in severe cases, result in acute respiratory distress syndrome (ARDS) [1, 2]. Secondary Infections in Severe COVID-19 of immunological reactions affecting the innate and adaptive immune responses, which are critical to the clinical course and outcome of patients. Consecutive activation of innate pattern recognition pathways may cause hyperinflammation during the antiviral immune response, leading to lung tissue damage and causing disruption of mucous membranes, contributing to an environment that allows for fungal infections [15,16,17,18]. Details regarding the susceptibility of these patients to Candida infection and characteristics of an impaired immune response have not been described yet
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