SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants

Abstract

Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T cells being linked to efficient viral clearance. Vaccination against SARS-CoV-2 induces both CD4+ and CD8+ T cell responses and permits protection from severe COVID-19, including infection with the currently circulating variants of concern. Nevertheless, in immunocompromised individuals, first data imply significantly impaired SARS-CoV-2-specific immune responses after both natural infection and vaccination. Hence, these high-risk groups require particular consideration, not only in routine clinical practice, but also in the development of future vaccination strategies. In order to assist physicians in the guidance of immunocompromised patients, concerning the management of infection or the benefit of (booster) vaccinations, this review aims to provide a concise overview of the current knowledge about SARS-CoV-2-specific cellular immune responses in the vulnerable cohorts of cancer patients, people living with HIV (PLWH), and solid organ transplant recipients (SOT). Recent findings regarding the virus-specific cellular immunity in these differently immunocompromised populations might influence clinical decision-making in the future.

Keywords: CD4+ T cells; CD8+ T cells; COVID-19; HIV; SARS-CoV-2; cancer; immunosuppression; mRNA vaccination; solid organ transplantation.

Figure 1

Infection-induced SARS-CoV-2-specific adaptive immune responses in cancer patients. (A) Hallmarks of the adaptive immune response following SARS-CoV-2 infection in cancer patients. (B) Phenotype of SARS-CoV-2-specific CD4+ and CD8+ T cells in patients suffering from hematologic cancer subtypes. (C) Brief summary of current knowledge about the influence of cancer subtypes or specific treatments on the development of SARS-CoV-2-specific adaptive immune responses upon infection. Created with BioRender.com, 2 February 2023.

Figure 2

Vaccine-induced SARS-CoV-2-specific adaptive immune responses in cancer patients. (A) Hallmarks of the adaptive immune response following SARS-CoV-2 vaccination in cancer patients. (B) Collection of first data addressing the effect of booster vaccine doses in patients suffering from different cancer subtypes. (C) Comparison of the distribution of cellular immune responses in hematologic cancer patients with or without seroconversion after SARS-CoV-2 vaccination. (D) Brief summary of current knowledge about the influence of specific treatments on the development of SARS-CoV-2-specific adaptive immune responses following vaccination. (E) Potential tools supporting the assessment or enhancement of vaccine-induced SARS-CoV-2-specific adaptive immune responses in cancer patients. Created with BioRender.com, 2 February 2023.

Figure 3

Infection-induced SARS-CoV-2-specific adaptive immune responses in PLWH. (A) Relationship between immune recovery under antiretroviral therapy (ART) and the risk of severe COVID-19 in PLWH. (B) Depiction of the influence of immune reconstitution under ART on the generation of virus-specific humoral and cellular immune responses upon SARS-CoV-2 infection in PLWH. Created with BioRender.com, 2 February 2023.

Figure 4

Vaccine-induced SARS-CoV-2-specific adaptive immune responses in PLWH. (A) Differences in the generation of SARS-CoV-2-specific polyfunctional (IFN-γ+IL-2+TNF+) CD4+ T cells following vaccination in PLWH and healthy controls (HC). (B) Depiction of the influence of immune reconstitution under ART on virus-specific humoral and cellular immune responses induced by SARS-CoV-2 vaccination in PLWH. (C) Collection of early data addressing the effect of booster vaccine doses in PLWH. (D) Illustration of first results pointing towards an inverse relationship between the influence of immune recovery under antiretroviral therapy (ART) and the number of vaccine doses in PLWH. Created with BioRender.com, 2 February 2023.

Figure 5

Infection-induced SARS-CoV-2-specific adaptive immune responses in SOT. (A) Characteristics of the SARS-CoV-2-specific cellular immune response in infected and convalescent SOT. (B) Brief summary of current knowledge about adaptive immune responses elicited by SARS-CoV-2 infection in kidney transplant recipients (KTR). (C) Illustration of challenges in the clinical management of SOT infected with SARS-CoV-2. (D) Brief summary of current knowledge about adaptive immune responses elicited by SARS-CoV-2 infection in liver transplant recipients (LTR). Created with BioRender.com, 2 February 2023.

Figure 6

Vaccine-induced SARS-CoV-2-specific adaptive immune responses in SOT. (A) Characteristics of the vaccine-induced cellular immunity in SOT. (B) Comparison of the amounts of polyfunctional virus-specific CD4+ T cells in vaccinated SOT and controls. (C) Brief summary of current knowledge about adaptive immune responses elicited by SARS-CoV-2 vaccination in kidney transplant recipients (KTR). (D) Brief summary of current knowledge about adaptive immune responses elicited by SARS-CoV-2 vaccination in liver transplant recipients (LTR). (E) Collection of early data addressing the effect of booster vaccine doses in SOT. Created with BioRender.com, 2 February 2023.