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COVID-19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)-T-cell therapy
Eleftheria Kampouri1,2, Joshua A Hill1,3,4, Veronica Dioverti5
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Insights
Immunocompromised patients, including those undergoing hematopoietic cell transplantation (HCT) and CAR-T therapy, face severe COVID-19 risks. New preventive strategies beyond vaccination are crucial due to inadequate immune responses.
Area of Science:
- Immunology
- Infectious Diseases
- Hematology
Background:
- Coronavirus disease 2019 (COVID-19) continues to pose significant risks to immunocompromised individuals, particularly those who have undergone hematopoietic cell transplantation (HCT) or chimeric antigen receptor-T-cell (CAR-T) therapies.
- These patient populations exhibit inadequate immune responses to vaccination, necessitating the exploration of alternative and supplementary preventive measures against severe COVID-19 and mortality.
Purpose of the Study:
- To review current and emerging therapeutic and preventive strategies for COVID-19 in immunocompromised patients.
- To highlight the unmet needs in managing COVID-19 in high-risk populations, including optimal vaccination protocols and novel treatment modalities.
Main Methods:
- Review of existing literature on COVID-19 management in immunocompromised hosts.
- Analysis of data regarding vaccine efficacy, antiviral therapies, convalescent plasma, and novel cell-based therapies.
Main Results:
- Vaccination provides insufficient protection in many immunocompromised patients, with optimal timing and correlates of immunity remaining unclear.
- Antiviral therapies, used early or in combination, show promise in reducing severity and preventing resistance.
- COVID-19 convalescent plasma is a potential option for mild-to-moderate cases, while protracted COVID-19 and intra-host variant emergence are significant concerns.
- Novel SARS-CoV2-specific T-cell and natural killer (NK) cell therapies demonstrate potential activity against multiple variants.
Conclusions:
- Immunocompromised patients require tailored COVID-19 prevention and treatment strategies beyond standard vaccination.
- Antiviral combinations, convalescent plasma, and advanced cell-based therapies represent promising avenues for managing COVID-19 in these vulnerable individuals.
- Further research is needed to establish optimal protocols and understand the long-term efficacy of novel therapeutic products.
Abstract:
More than 3 years have passed since Coronavirus disease 2019 (COVID-19) was declared a global pandemic, yet COVID-19 still severely impacts immunocompromised individuals including those treated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor-T-cell therapies who remain at high risk for severe COVID-19 and mortality. Despite vaccination efforts, these patients have inadequate responses due to immunosuppression, which underscores the need for additional preventive approaches. The optimal timing, schedule of vaccination, and immunological correlates for protective immunity remain unknown. Antiviral therapies used early during disease can reduce mortality and severity due to COVID-19. The combination or sequential use of antivirals could be beneficial to control replication and prevent the development of treatment-related mutations in protracted COVID-19. Despite conflicting data, COVID-19 convalescent plasma remains an option in immunocompromised patients with mild-to-moderate disease to prevent progression. Protracted COVID-19 has been increasingly recognized among these patients and has been implicated in intra-host emergence of SARS-CoV-2 variants. Finally, novel SARS-CoV2-specific T-cells and natural killer cell-boosting (or -containing) products may be active against multiple variants and are promising therapies in immunocompromised patients.
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