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Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh
Taufiqur Rahman Bhuiyan1, Hasan Al Banna1, M Hasanul Kaisar1
1Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh.
Insights
COVID-19 infection impacts T cell responses. Symptomatic patients showed reduced mucosal-associated invariant T cells and increased natural killer cells, while severe cases exhibited robust CD4+ T cell activation, suggesting a key role in SARS-CoV-2 immunity.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) presents with varied severity.
- Antigen-specific T cells are crucial for protective immunity against SARS-CoV-2.
- Understanding T cell dynamics during COVID-19 is vital for vaccine and therapeutic development.
Purpose of the Study:
- To evaluate activation-induced marker (AIM) expression and immune cell subset changes during COVID-19.
- To investigate T cell responses in relation to clinical severity of COVID-19.
- To assess the role of T cells in SARS-CoV-2 infection and recovery.
Main Methods:
- Longitudinal cohort study in Bangladesh with 115 participants (asymptomatic to severe COVID-19).
- Analysis of mucosal-associated invariant T (MAIT) cells, natural killer (NK) cells, and CD4+/CD8+ T cell activation markers (AIM).
- Use of SARS-CoV-2 peptides, particularly spike peptides, for T cell stimulation.
Main Results:
- Symptomatic COVID-19 patients had decreased MAIT cell frequency initially.
- Elevated NK cell counts were observed in symptomatic patients early in the disease.
- Moderate and severe COVID-19 patients showed increased CD4+ T cell AIMs (OX40+CD137+, OX40+CD40L+) against SARS-CoV-2 peptides.
- No significant difference in CD8+ T cell AIMs (CD137+CD69+) was noted, suggesting CD8+ T cell exhaustion.
Conclusions:
- COVID-19 alters circulating immune cell populations, including MAIT and NK cells.
- A strong CD4+ T cell response against SARS-CoV-2 antigens is mounted in moderate to severe COVID-19.
- CD8+ T cell exhaustion may occur during SARS-CoV-2 infection.
- CD4+ T cell responses are critical for adaptive immunity and recovery from severe COVID-19.
Abstract:
Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.
