Recent findings on T-cell immunity induced by SARS-CoV-2 infection and vaccination in immunocompromised individuals

By Dr. Chinta SidharthanFeb 8 2023Reviewed by Danielle Ellis, B.Sc.

In a recent review published in Pathogens, researchers discussed studies that explored T-cell immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination in cancer patients, individuals with human immunodeficiency virus (HIV), and recipients of solid organ transplants.

Background

The adaptive immune responses induced by SARS-CoV-2 infection and COVID-19 vaccinations consist of the humoral B-cell and antibody-mediated immunity and the early activation of the T-cell responses, which help in viral elimination. While antibody titers have been considered an indicator of protection against SARS-CoV-2, higher levels of T-cells specific to SARS-CoV-2 have been associated with a lower risk of disease severity and death. Furthermore, unlike humoral immunity, the T-cell targeted epitopes are largely conserved across the SARS-CoV-2 variants of concern.

However, most studies evaluating SARS-CoV-2-specific T-cell responses have focused on otherwise healthy individuals. Little is known about the T-cell responses elicited by SARS-CoV-2 infections or COVID-19 vaccination in immunocompromised individuals. Therefore, a better understanding of the SARS-CoV-2-specific T-cell responses in immunocompromised patients, such as those with cancer, HIV, or recent organ transplants, is essential for future decisions on vaccinations and COVID-19 management.

T-cell responses in cancer patients

The review found that COVID-19 susceptibility differed across the cancer subtypes, possibly due to the varying impairment levels in the adaptive immunity against SARS-CoV-2. Compared to healthy individuals, cancer patients had weaker CD8+ and CD4+ T-cell responses against SARS-CoV-2. Furthermore, patients with hematological cancers were at an increased risk of developing upper respiratory tract infections, including COVID-19, due to higher levels of immunosuppression.

Studies have shown that hematological cancer patients with higher levels of CD8+ T-cells had a better chance of recovery and survival than those with lower CD8+ levels. Moreover, while the detectable CD4+ T-cell levels were 81% in patients with solid tumors, hematological cancer patients had only 58% CD4+ T-cells. The CD8+ T-cell levels detected in solid tumor and hematological cancer patients were 51% and 42%, respectively. These results indicated that patients with hematological cancers would benefit from monoclonal antibody treatments and prophylactic vaccines against SARS-CoV-2.

Cancer patients have also shown prolonged infection and a reduced rate of SARS-CoV-2 clearance. Compared to patients with solid tumors, hematological cancer patients have exhibited higher viral loads, and positive polymerase chain reaction (PCR) tests for longer.

Furthermore, the T-cell responses elicited by messenger ribonucleic acid (mRNA) or vector-based COVID-19 vaccines in cancer patients were also significantly lower compared to healthy individuals. A single dose of the BNT162b2 vaccine induced lower levels of interferon-gamma (IFN-γ) and interleukin-2 (IL-2) producing T-cells in solid tumor and hematological cancer patients.

T-cell responses in HIV patients

People with HIV, especially those with reduced viral suppression and low counts of CD4+ T-cells, were found to be at a significantly high risk of severe COVID-19 and hospitalization. Compared to HIV patients with controlled viremia, patients with unsuppressed HIV infection had lower levels of SARS-CoV-2-specific IFN-γ and tumor necrosis factor-alpha (TNF-α) producing T-cells. Still, no differences in the CD8+ T-cell levels were detected.

Furthermore, unlike the pattern in healthy individuals, the CD4+/CD8+ ratio did not increase in HIV patients with SARS-CoV-2 infections, suggesting that this parameter could be used as a risk stratification indicator. Additionally, patients receiving antiretroviral therapy (ART) were seen to have reduced COVID-19 severity and risk of mortality compared to those not receiving ART. Interestingly, people with HIV, especially those receiving ART, also elicited robust T-cell responses after getting vaccinated with mRNA or vector-based COVID-19 vaccines.

T-cell responses in solid organ transplant patients

Compared to immunocompetent individuals, patients on immunosuppressive therapy after undergoing solid organ transplants such as those of the heart, kidney, or liver showed slightly decreased cytokine-producing SARS-CoV-2-specific T-cell levels in the early stages of the infection. However, the T-cell levels in both groups were comparable at about 30 days after the onset of COVID-19 symptoms. The T-cell responses were also seen to differ based on the severity of the SARS-CoV-2 infection, similar to the pattern in healthy individuals.

Two doses of the mRNA COVID-19 vaccine were seen to elicit significantly lower T-cell responses compared to healthy individuals and even patients with HIV and primary immunodeficiencies. Booster vaccine doses, temporary immunosuppressive therapy adjustments, as well as heterologous vaccine regimens have been proposed to enhance the vaccine-induced T-cell responses in solid organ transplant patients.

Conclusions

Overall, the review indicated that across various immunocompromised groups, the differences in individual disease conditions and therapies influence the SARS-CoV-2-specific T-cell responses induced by SARS-CoV-2 infections and vaccinations. Cancer subtypes, ART in HIV patients, and immunosuppression therapy levels in solid organ transplant patients play a role in the T-cell responses against SARS-CoV-2.

These results highlight the differing T-cell responses between immunocompromised and healthy individuals, which can help guide physicians in the management and treatment of COVID-19 in immunosuppressed patients.