Dynamic SARS-CoV-2-Specific Immunity in Critically Ill Patients With Hypertension

Abstract

Background: The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear.

Methods: In total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38⁺HLA-DR⁺ and CD38⁺PD-1⁺ CD8⁺ T cells, IFNγ⁺CD4⁺ and IFNγ⁺CD8⁺ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored.

Findings: CD4⁺ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38⁺HLA-DR⁺ and CD38⁺PD-1⁺ on CD8⁺ T cells, low expression of SARS-CoV-2-specific IFNγ⁺CD4⁺ and IFNγ⁺CD8⁺ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFNγ⁺CD8⁺and IFNγ⁺CD4⁺ T cells, IgG, IgM, and IgA.

Interpretation: T lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8⁺ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.

Keywords: CD4; CD8; COVID-19; SARS-CoV-2; T cell; hypertension.