Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function

Background It has been proven that inactivated COVID-19 vaccines are safe and effective in general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). Methods 42 HIV-1 infected individuals who were stable on cART and 28 healthy individuals were enrolled in this study. Two doses of an inactivated COVID-19 vaccine (BIBP-CorV) were given 4 weeks apart. The safety and reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. Findings All the HIV-1 infected participants had a CD4+ T cell count of above 200 cells/μL both at baseline and 4 weeks after vaccination. No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. Further analyses showed that PLWH with low baseline CD4+/CD8+ T cell ratios (<0.6) generated lower antibody responses after vaccination than PLWH with medium (0.6~1.0) or high (≥1.0) baseline CD4+/CD8+ T cell ratios (P<0.01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination, but it did not lead to any adverse clinical manifestation. Moreover, we found that the general burden of HIV-1 among the PLWH cohort decreased significantly (P=0.0192) after vaccination. And the alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation. Interpretation Our data demonstrate that the inactivated COVID-19 vaccine is safe and immunogenic in PLWH who are stable on cART with unsuppressed CD4 counts. Funding This work was funded by the National Natural Science Foundation of China (Grant No. 81971559, 82041010).

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COVID-19 in multiple-myeloma patients: cellular and humoral immunity against SARS-CoV-2 in a short- and long-term view

Journal of Molecular Medicine ◽

10.1007/s00109-021-02114-x ◽

2021 ◽

Author(s):

Ivana von Metzler ◽

Julia Campe ◽

Sabine Huenecke ◽

Marc S. Raab ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Immune Response ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Tumor Therapy ◽

Cd4 T Cell ◽

List Type ◽

Cell Counts ◽

Antibody Titers

Abstract Multiple myeloma patients are often treated with immunomodulatory drugs, proteasome inhibitors, or monoclonal antibodies until disease progression. Continuous therapy in combination with the underlying disease frequently results in severe humoral and cellular immunodeficiency, which often manifests in recurrent infections. Here, we report on the clinical management and immunological data of three multiple-myeloma patients diagnosed with COVID-19. Despite severe hypogammaglobulinemia, deteriorated T cell counts, and neutropenia, the patients were able to combat COVID-19 by balanced response of innate immunity, strong CD8+ and CD4+ T cell activation and differentiation, development of specific T-cell memory subsets, and development of anti-SARS-CoV-2 type IgM and IgG antibodies with virus-neutralizing capacities. Even 12 months after re-introduction of lenalidomide maintenance therapy, antibody levels and virus-neutralizing antibody titers remained detectable, indicating persisting immunity against SARS-CoV-2. We conclude that in MM patients who tested positive for SARS-CoV-2 and were receiving active MM treatment, immune response assessment could be a useful tool to help guide decision-making regarding the continuation of anti-tumor therapy and supportive therapy. Key messages Immunosuppression due to multiple myeloma might not be the crucial factor that is affecting the course of COVID-19. In this case, despite pre-existing severe deficits in CD4+ T-cell counts and IgA und IgM deficiency, we noticed a robust humoral and cellular immune response against SARS-CoV-2. Evaluation of immune response and antibody titers in MM patients that were tested positive for SARS-CoV-2 and are on active MM treatment should be performed on a larger scale; the findings might affect further treatment recommendations for COVID-19, MM treatment re-introduction, and isolation measures.

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