T‐cell dysfunction as a potential contributing factor in post‐COVID‐19 mucormycosis

Abstract 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.