Exploring SARS-CoV-2 vaccine responsiveness in immunosuppressed patients

The coronavirus-induced-disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified as a local pneumonia outbreak in Wuhan, China in late 2019. The local outbreak of pneumonia rapidly progressed into a global pandemic leading to mass morbidity, mortality, and significant socio-economic turmoil.

Mass vaccination programs have been considered the best way to prevent viral transmission, severe disease, and death due to COVID-19. Currently, four vaccines have been approved by the European Medicines Agency. However, the clinical trials resulting in vaccine approval involved only healthy individuals. No immunosuppressed patients were included in the trial although they have been considered clinically vulnerable to COVID-19. Therefore, ambiguity regarding vaccine efficacy in immunosuppressed patients remains.

Study: Cellular and humoral responses to SARS-CoV-2 vaccination in immunosuppressed patients. Image Credit: 3DJustincase/ShutterstockStudy: Cellular and humoral responses to SARS-CoV-2 vaccination in immunosuppressed patients. Image Credit: 3DJustincase/Shutterstock

Spike protein-specific neutralizing antibodies are found to be generated both after vaccination and natural infection. However, several studies have indicated the lowering of these antibody levels over time. In contrast, studies have indicated the long-term impact of SARS-CoV-2 T-cell responses. The SARS-CoV-2 specific T cells were detected six to eight months after post-infection while no antigen-specific B-memory cells or antibodies were detected six months post-infection.

A new study published in the pre-print server medRxiv* assessed both cellular and humoral responses in immunocompromised individuals especially those with kidney-transplant or hematological malignancies.

The study

The study involved healthy unvaccinated COVID-19-infection naïve participants, vaccinated and unvaccinated healthcare workers, and vaccinated immunocompromised individuals. Blood samples were collected from the participants for serological assays. T-cell ELISpot analysis was carried out to isolate peripheral blood mononuclear cells (PBMCs) from the blood that would finally detect SARS-CoV-2 T-cells.

Thereafter, SARS-CoV-2 cellular immunophenotyping was done using the harvest PBMCs followed by flow cytometry, serological testing, and Th1 cytokine profiling.

Study findings

The results indicated that among the unvaccinated cohort, comorbidities such as sleep apnoea, hypothyroidism, and stroke were reported. Nine unvaccinated participants had mild COVID-19 symptoms while two required hospitalization. Among the vaccinated immunocompetent cohort comorbidities such as depression and mild asthma were detected.

Among the immunocompromised cohort, 7 patients had end-stage renal disease and received renal transplantation, four had hematological malignancies, two had autoimmune disorders, and twelve had other comorbidities which were high-risk for COVID-19. The immunocompromised patients were under immunosuppressive treatments except for three who were not under any treatment. Most of the patients had suffered from mild or severe COVID-19 infection while few required hospitalization.

The results found that the cellular spike peptide response was very low in the unvaccinated cohort. The immunocompromised participants showed a higher cellular response although there was one participant who showed no cellular response. However, the nucleocapsid and membrane peptide responses were lower as compared to the spike peptide response among all the groups.

Furthermore, higher anti-spike serological responses were observed in both immunocompetent and immunocompromised cohorts as compared to the unvaccinated cohort. The humoral response between the vaccinated immunosuppressed patients and the vaccinated immunocompetent cohort was found to be comparable.

Following stimulation with spike peptide, both CD4+ and CD8+ upregulated HLA-DR+ T cells while higher CD38+ was observed only in CD4+ T-cells. A higher T-cell activation profile was observed in CD8+ as compared to CD4+ after nucleocapsid peptide stimulation. However, the immunocompromised patients showed lower proportions of specific T cell meta clusters upon stimulation with either spike, nucleocapsid, or membrane peptides.

The CD4+ naïve (Tn) and effector (Te) cells were found to be higher in the immunocompetent cohort as compared to the immunocompromised cohort while the CD4+ T-effector-memory (Tem) was found to be higher in the immunocompromised cohort. However, a similar T-central memory population was observed between both groups. A similar result was obtained with the CD8+ subsets. Moreover, an increase in CD8+ Te as compared to CD4+ Te was observed in both the groups along with Tem being identified as the predominant memory T-cell subset across both the groups.

The study also reported that the magnitude of cytokine secretion was observed across all the cohorts with IL-6, TNFα, and IL-1β levels being significantly higher as compared to  IL-10 that suggests a strong bias towards Th1 cytokine secretion following stimulation.

Overall, the current study indicates an immunological response to SARS-CoV-2 vaccines in immunosuppressed patients that were comparable to healthy patients. The study also highlights the impact of SARS-CoV-2 specific T-cells. However, further research is required to decipher the humoral and cellular responses as well as evaluate if the longevity of these responses is comparable to healthy individuals.

Limitations

The study had certain limitations. First, the study population was small and restricted to patients with renal transplants and hematological malignancies. Second, demographic risk factors for COVID-19 were not investigated. Finally, only a small proportion of vaccinated healthy and immunosuppressed cohorts were able to re-bleed for T-cell subset analysis.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Suchandrima Bhowmik

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.

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