COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses

Abstract

Highlights d high SARS-CoV-2 IgG but overall reduced T cell immunity in active COVID-19 patients d PD-1, Tim-3, and active caspases in T cells result in impaired T cell function d stable SARS-CoV-2 T cell repertoire yet declining humoral responses during recovery d potentially protective role of pre-existing anti-huCoV CD4 + and CD8 + T cell immunity

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients

“…A similar outcome and benefit of pre-existing T cell immunity have been shown in the case of flu pandemic virus H1N1 (41,42). However, active stimulation of cross-reactive T cells could also lead to exhaustion of rapidly expanded T cells, similar to the higher PD-1 expression and reduced cytokine secretion of the SARS-CoV-2 immunodominant T cells observed by us and others (5,43,44). Additionally, hyperactivation of pre-existing T cells could contribute to short-and long-term disease severity via inflammation and autoimmunity, as increased production of IFN-γ by CD4 + and CD8 + T cells has been observed in severe COVID-19 patients (45).…”

Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies

“…In addition to a humoral mediated immune response, T cell-mediated immune response plays a role in SARS-CoV-2 infection and the specific cellular immunity may be more stable and longer lasting than humoral immunity [ 38 , 39 ]. This is particularly of interest regarding the immunity of recovered patients with low or no detectable neutralizing antibodies [ 40 ].…”

Development of T-cell immunity in a liver and hematopoietic stem cell transplant recipient following coronavirus disease 2019 infection

“…Importantly, our analysis extended beyond the S1 and S2 antigens, commonly examined in the context of the currently approved anti-COVID-19 vaccines, but also includes the far less studied M and NP proteins from SARS-CoV2 and all four common hCoVs suggesting possible heterologic cross-protection against future infections including emerging mutant variants of SARS-CoV2 and other members of CoV family [6] . Recent evidence suggests that there might be a tendency for a milder course of the disease in COVID-19 patients who had recently experienced hCoV-related infections with some cross-reactive antibodies increasing post-COVID [ 10 , [21] , [22] , [23] ]. Unfortunately, in the patient described here magnitude and breath of the pre-existing T cell memory specific for hCoV antigens is unknown.…”

“…Although cellular adaptive immunity against COVID-19 mediated by T cells is less understood, emerging data suggest that T cell responses may be long-lived and crucial in mediating protection against re-infection, possibly well beyond the period of seropositivity [6] , [7] , [8] , [9] , [10] . The extent and magnitude of humoral and cellular immunity in vulnerable transplant recipients who survived COVID-19 remains poorly characterized [11] .…”