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Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19
Rohan Ameratunga1, Hilary Longhurst2, Richard Steele3
1Department of Clinical Immunology, Auckland Hospital, Auckland, New Zealand; Department of Virology and Immunology, Auckland Hospital, Auckland, New Zealand; Department of Molecular Medicine and Pathology, School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Insights
Patients with primary immunodeficiency (PID) face severe COVID-19 risks due to impaired immunity and vaccine response. Prioritizing vaccination and prevention of chronic COVID-19 is crucial for this vulnerable population.
Area of Science:
- Immunology and Infectious Diseases
- Virology
- Public Health
Background:
- COVID-19 significantly impacts global health, with immune responses not fully understood.
- Comorbidities like obesity and diabetes, alongside age and ethnicity, increase severe COVID-19 risk.
- Primary immunodeficiency (PID) and secondary immunodeficiency patients are at heightened risk, often with chronic pulmonary issues and poor vaccine responses.
Purpose of the Study:
- To highlight the increased risk of severe COVID-19 and chronic COVID-19 in patients with primary immunodeficiency disorders (PID).
- To emphasize the urgent need for vaccination and prevention strategies in immunodeficient individuals.
- To underscore the importance of assessing T-cell immunity for vaccine response evaluation and developing targeted treatments.
Main Methods:
- Review of existing literature on COVID-19 outcomes in immunocompromised populations.
- Analysis of risk factors including age, ethnicity, comorbidities, and specific immunodeficiencies (e.g., Common Variable Immunodeficiency Disorders).
- Discussion of viral evolution, vaccine resistance, and the role of T-cell immunity diagnostics.
Main Results:
- Patients with PID, particularly Common Variable Immunodeficiency Disorders, exhibit a spectrum of B- and T-cell defects, increasing susceptibility to severe and chronic COVID-19.
- Risk stratification may be possible based on age, ethnicity, T-cell defect severity, and comorbidities.
- Intra-host viral evolution poses a risk for vaccine-resistant variants, creating a public health emergency.
Conclusions:
- Vaccination and prevention of chronic COVID-19 are paramount for immunodeficient patients.
- Reliable diagnostic assays for T-cell immunity are critical for evaluating vaccine efficacy in this group.
- Novel treatments like NZACE2-Pātari may benefit immunodeficient patients, especially those with suboptimal T-cell responses to vaccines.
Abstract:
COVID-19 has had a calamitous effect on the global community. Despite intense study, the immunologic response to the infection is only partially understood. In addition to older age and ethnicity, patients with comorbidities including obesity, diabetes, hypertension, coronary artery disease, malignancy, renal, and pulmonary disease may experience severe outcomes. Some patients with primary immunodeficiency (PID) and secondary immunodeficiency also appear to be at increased risk from COVID-19. In addition to vulnerability to SARS-CoV-2, patients with PIDs often have chronic pulmonary disease and may not respond to vaccines, which exacerbates their long-term risk. Patients with common variable immunodeficiency disorders, the most frequent symptomatic PID in adults and children, have a spectrum of B- and T-cell defects. It may be possible to stratify their risk for severe COVID-19 based on age, ethnicity, the severity of the T-cell defect, and the presence of other comorbidities. Patients with common variable immunodeficiency disorders and other immunodeficiencies are at risk for Chronic COVID-19, a dangerous stalemate between a suboptimal immune response and SARS-CoV-2. Intra-host viral evolution could result in the rapid emergence of vaccine-resistant mutants and variants of high consequence; it is a public health emergency. Vaccination and prevention of Chronic COVID-19 in immunodeficient patients is therefore of the utmost priority. Having a reliable diagnostic assay for T-cell immunity to SARS-CoV-2 is critical for evaluating responses to vaccines in these patients. New treatments for SARS-CoV-2 such as NZACE2-Pātari are likely to be particularly beneficial for immunodeficient patients, especially those who fail to mount a robust T-cell response to COVID-19 vaccines.
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