Compartmental t-cell profile and IFN response in SARS-CoV-2-infected subjects

ABSTRACT

Background: A severe SARS-CoV-2 related immunopathology may be the driver cause underlying the deleterious clinical manifestations observed in COVID-19 patients. To identify possible tissue-specific immune responses patterns, a compartmental immunophenotyping analysis of CD4+ and CD8+ T lymphocytes and IFN response has been performed in SARS-CoV-2 infected subjects with acute respiratory distress syndrome. Methods: Bronchoalveolar lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) samples were collected from 13 SARS-CoV-2 infected subjects (9 males and 4 females) consecutively admitted to intensive care unit (ICU) of Policlinico Umberto I, Sapienza University Hospital in Rome (Italy). The frequencies of CD4+, CD8+ T lymphocytes and those expressing immune activation markers (CD38, HLADR), naïve, central memory (CMEM), and effector memory (TEM) T cell subsets were evaluated in both anatomical sites by multiparametric flow cytometry. Gene expression levels of Interferon regulatory factor 7 (IRF7) and the Interferon Stimulated Gene 15 (ISG15) were evaluated in BAL and PBMC by Real-time PCR. Results: Critically SARS-CoV-2 infected patients exhibited a lung compartmentalization of CD8+ T cells (p=0.003), with a lower CD4/CD8 ratio in BAL compared to blood district (p<0.01). However, higher frequencies of CD8+ T cells were recorded in PBMC of female SARS-CoV-2 infected patients (p=0.04) and the same trend was observed in the lung compartment. By contrast, a trend of increasing CD4+ T cells frequencies was observed in BAL samples of male patients, as opposed to blood compartment. Additionally, an increased expression of immune activation markers CD38 and HLADR has been detected in BAL CD8+ T cells (p<0.01) as well as in blood CD4+ T cells (p=0.03). An increased frequency of CD4+ and CD8+ TEM cells has been documented in BAL of SARS-CoV-2 infected patients (p<0.05), as opposed to higher frequencies of CD4+ and CD8+ TCM cells recorded in the blood compartment (p<0.01). Notably, higher levels of ISG15 and IRF7 found in BAL were inversely associated to activated CD8+ T cell frequencies in the lung compartment compared to blood district (ISG15 r=-0.570, p<0.05) (IRF7 r=-0.683, p=0.01). Conclusion: Our findings provide new insight into a distinct T cells profile and IFN genes expression in the lung and in the blood compartment of SARS-CoV-2 infected patients, that might be highly relevant for the clinical course of COVID-19.