Immunosuppression as a Hallmark of Critical COVID-19: Prospective Study

Abstract

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients

“…A lower number of T cells at COVID-19 onset was reported to be a marker of progression to severe disease [ 54 ]. Lower levels of T helper cells, T suppressor cells, T regulatory cells, and CD16 + CD56 + NK cells were reported in critical COVID-19 patients compared with non-critical COVID-19 patients, with impairments in the function of T and NK cells and very low levels of secreted cytokines [ 55 ]. However, Thieme reported that a robust anti-spike, membrane, and nucleocapsid SARS-CoV-2 protein T cell response was not associated with recovery in critical COVID-19 patients [ 56 ].…”

Cytokine Storms in the Course of COVID-19 and Haemophagocytic Lymphohistiocytosis in Pregnant and Postpartum Women

“…In addition to this, the total T lymphocytes, CD4+, CD8+ T lymphocytes and B lymphocyte counts were found to be significantly decreased in severe and critically ill patients on their admission. These results show that SARS-CoV-2 has a negative effect on T-cell mediated immunity [34].…”

COVID-19 and Psychotic Symptoms: the View from Psychiatric Immunology

“…Immunological changes are one of the hallmarks of COVID-19 [ 18 ]. A study on COVID-19 patients had revealed that the function of T cells and natural killer (NK) cells is critically altered in severely ill patients [ 18 ].…”

“…Immunological changes are one of the hallmarks of COVID-19 [ 18 ]. A study on COVID-19 patients had revealed that the function of T cells and natural killer (NK) cells is critically altered in severely ill patients [ 18 ]. It is found that the ratio between interleukin-2 (IL-2) and interferon-gamma (IFN- γ ) is one of the sensitive indicators of outcome and disease progression [ 18 ].…”

“…A study on COVID-19 patients had revealed that the function of T cells and natural killer (NK) cells is critically altered in severely ill patients [ 18 ]. It is found that the ratio between interleukin-2 (IL-2) and interferon-gamma (IFN- γ ) is one of the sensitive indicators of outcome and disease progression [ 18 ]. However, current evidence showed a high concentration of interleukin-6 (IL-6) related to severe illness [ 11 •].…”