Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era

Zhang, Tingting; Tian, Wei; Wei, Shuang; Lu, Xinyi; An, Jing; He, Songtao; Zhao, Jie; Gao, Zhilin; Li, Li; Lian, Ke; Zhang, Qiang; Zhang, Huilai; Wang, Liang; Hj, Kang; Niu, Ting; Zhao, Ailin; Pan, Jing; Cai, Qing-Qing; Xu, Zhenshu; Chen, Wen-Ming; Jing, Hongmei; Li, Peng; Zhao, Wei; Cao, Yang; Mi, Jian-Qing; Chen, Tao; Chen, Yuan; Zou, Ping; Lukacs‐Kornek, Veronika; Kurts, Christian; Li, Jian; Liu, Xiansheng; Mei, Qi; Zhang, Yicheng; Wang, Jia

doi:10.1186/s40164-023-00426-x

Cited by 8 publications

(9 citation statements)

References 154 publications

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“…Recent study indicates a disease severity-dependent TCR clonal expansion pattern in COVID-19 patients, demonstrating that the disease-specific TCRs is required for symptomatic relief [ 5 ]. However, the landscape of T-cell receptor (TCR) repertoires in COVID-19 and the TCRs responsible for recognizing SARS-CoV-2 remain uncertain [ 6 , 7 ].…”

Section: To the Editormentioning

confidence: 99%

Identification of SARS-CoV-2-specific T cell and its receptor

Zhang,

Liang,

Zhang

et al. 2024

J Hematol Oncol

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The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies.

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Section: To the Editormentioning

confidence: 99%

Identification of SARS-CoV-2-specific T cell and its receptor

Zhang,

Liang,

Zhang

et al. 2024

J Hematol Oncol

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“…Despite the lower seroconversion rates observed in HM patients, substantial evidence supports the clinical benefit of COVID-19 vaccination, with emerging data indicating a dose–response relationship [ 89 , 100 ]. A higher number of vaccine doses received before COVID-19 infection is associated with significantly lower mortality rates, highlighting the benefit of booster doses in providing optimal protection to this vulnerable group [ 89 ].…”

Section: Covid-19 Management In Individuals With Hmsmentioning

confidence: 99%

“…CAR-T recipients showed improved serological response rates with each additional vaccine dose, reaching 75% after four doses compared to 20.4% after one dose [ 9 ]. Furthermore, anti-spike antibody titers were more than 30 times higher after four doses compared to two doses [ 100 ]. Based on emerging data and the evolving context of COVID-19, revised vaccination recommendations for patients with HM and HSCT (Table 1 ) now include a three-dose primary schedule followed by an additional vaccine dose.…”

Section: Covid-19 Management In Individuals With Hmsmentioning

confidence: 99%

Managing and treating COVID-19 in patients with hematological malignancies: a narrative review and expert insights

Ng,

Alata,

Nguyen

et al. 2024

Clin Exp Med

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Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.

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“… 37 Over the years, several SARS-CoV-2 variants have emerged, with varying risks of morbidity, including Alpha, Beta, Gamma, Delta and Omicron, with multiple subvariants and sub-branches. 39 The outcomes vary by variant, and are worse in those patients with lymphopenia, higher ferritin and who develop COVID-19 close to infusion. 38,40,41 Therapies such as remdesivir, nirmatrelvir/ritonavir and immunizations have contributed to improved outcomes in recent years.…”

Section: The Emergence Of Infections As a Significant Concernmentioning

confidence: 99%

Managing Infection Complications in the Setting of Chimeric Antigen Receptor T cell (CAR-T) Therapy

Ahmed,

Oluwole,

Mahmoudjafari

et al. 2024

Clinical Hematology International

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Chimeric antigen receptor T-cell (CAR T-cell) therapy has changed the paradigm of management of non-Hodgkin’s lymphoma (NHL) and Multiple Myeloma. Infection complications have emerged as a concern that can arise in the setting of therapy and lead to morbidity and mortality. In this review, we classified infection complications into three categories, pre-infusion phase from the time pre- lymphodepletion (LD) up to day zero, early phase from day of infusion to day 30 post-infusion, and late phase after day 30 onwards. Infections arising in the pre-infusion phase are closely related to previous chemotherapy and bridging therapy. Infections arising in the early phase are more likely related to LD chemo and the expected brief period of grade 3-4 neutropenia. Infections arising in the late phase are particularly worrisome because they are associated with adverse risk features including prolonged neutropenia, dysregulation of humoral and adaptive immunity with lymphopenia, hypogammaglobinemia, and B cell aplasia. Bacterial, respiratory and other viral infections, protozoal and fungal infections can occur during this time . We recommend enhanced supportive care including prompt recognition and treatment of neutropenia with growth factor support, surveillance testing for specific viruses in the appropriate instance, management of hypogammaglobulinemia with repletion as appropriate and extended antimicrobial prophylaxis in those at higher risk (e.g. high dose steroid use and prolonged cytopenia). Finally, we recommend re-immunizing patients post CAR-T based on CDC and transplant guidelines.

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Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era

Cited by 8 publications

References 154 publications

Identification of SARS-CoV-2-specific T cell and its receptor

Identification of SARS-CoV-2-specific T cell and its receptor

Managing and treating COVID-19 in patients with hematological malignancies: a narrative review and expert insights

Managing Infection Complications in the Setting of Chimeric Antigen Receptor T cell (CAR-T) Therapy

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