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

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.