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T-cell dysfunction as a potential contributing factor in post-COVID-19 mucormycosis
Himanshu Dandu1, Manish Kumar2, Hardeep Singh Malhotra3
1Department of Internal Medicine, King George's Medical University, Lucknow, India.
Background:
The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases such as diabetes, cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis.
Objective:
To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients.
Material And Method:
The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry.
Results:
All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4+ T cells for HLADR and CD38 (p = .025, p = .054) and marked T-cell exhaustion in form of expression of LAG-3 on both CD4+ T and CD8+ T cells in comparison with post-COVID patients (p = .011, p = .036). Additionally, co-expression of PD-1 & LAG-3 and LAG-3 & TIM-3 on CD8+ T cells was statistically significant in non-COVID mucor patients (p = .016, p = .027).
Conclusion:
Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.
Insights
T-cell exhaustion is more severe in non-COVID mucormycosis than in post-COVID cases, leading to poorer outcomes. This study highlights differences in T-cell immune dysfunction between these patient groups.
Area of Science:
- Immunology
- Infectious Diseases
- Oncology
Background:
- The second wave of COVID-19 in India saw a rise in mucormycosis cases, often linked to immunosuppressive drugs and underlying conditions.
- While mucormycosis cases increased post-COVID-19, their mortality rates were lower than in non-COVID mucormycosis cases.
Purpose of the Study:
- To investigate detailed T-cell characteristics in post-COVID and non-COVID mucormycosis patients.
- To identify underlying differences in T-cell immune dysfunction between these groups.
Main Methods:
- Histopathologically confirmed mucormycosis cases (13 post-COVID, 13 non-COVID) and 15 healthy individuals were studied.
- Flow cytometry was used to evaluate T-cell activation markers (CD44, HLADR, CD69, CD38) and exhaustion markers (CTLA, PD-1, LAG-3, TIM-3).
Main Results:
- All mucormycosis patients exhibited significant T-cell depletion compared to healthy individuals.
- Both post-COVID and non-COVID groups showed increased T-cell activation and exhaustion.
- Non-COVID mucormycosis patients displayed significantly higher CD4+ T-cell activation (HLADR, CD38) and marked T-cell exhaustion (LAG-3 expression on CD4+ and CD8+ T cells) compared to post-COVID patients.
Conclusions:
- Non-COVID mucormycosis cases exhibit more pronounced T-cell exhaustion than post-COVID cases.
- T-cell immune dysfunction appears more severe in non-COVID mucormycosis, characterized by continuous activation followed by extreme exhaustion.
- These findings suggest a link between the severity of T-cell immune dysfunction and patient outcomes in mucormycosis.
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