The immunology of long COVID

The study “The immunology of long COVID” provides comprehensive insights into the complex immunological aspects of long COVID.

Here’s a summary:

  1. Overview of Long COVID: Long COVID refers to persistent symptoms following a COVID-19 infection, affecting an estimated 10% of those who contracted the virus. The symptoms vary from mild to debilitating and affect multiple organs and systems. They include fatigue, breathlessness, neurocognitive effects, and dysautonomia. Long COVID may be stratified into distinct entities with different pathogenic pathways​​.
  2. Possible Mechanisms: The study discusses various potential mechanisms of long COVID, including persistent SARS-CoV-2 reservoirs, abnormal immune responses to acute COVID-19, reactivation of viruses like Epstein–Barr virus (EBV), systemic immune perturbations, autoimmunity affecting the autonomic nervous system, coagulopathy, and microbiome dysbiosis​​.
  3. Abnormal Antiviral Immune Response: Studies have suggested a link between the risk of long COVID and abnormal immune responses during acute infection. This includes both overly aggressive and inadequately controlled immune responses, which might not efficiently clear the virus, leading to persistent symptoms​​.
  4. Role of Latent Virus Reactivation: EBV reactivation has been linked to long COVID, with studies showing increased EBV seroreactivity among long COVID patients. This reactivation could potentially contribute to long COVID immunopathogenesis through immune subset perturbation and autoantibody release​​.
  5. Systemic Immunity Perturbations: Long COVID might involve long-term disruption or changes in adaptive immunity, as indicated by global increases in PD1 expression by T cells and depletion of naive subsets. This could result from bystander activation or cytokine activation​​.
  6. Omics Approaches to Predict Long COVID: Omics studies have been used to predict who might develop persistent symptoms post-infection. These studies have identified biosignatures and differential immune phenotypes associated with long COVID, such as low serum cortisol levels and elevated proteins related to circadian regulation in those with neurological symptoms​​.
  7. Multi-dimensional Immune Phenotyping: A study focusing on non-hospitalized long COVID patients identified reduced serum cortisol and increases in IL-8 and CCL4 as significant biomarkers. Flow cytometry of peripheral blood mononuclear cells (PBMCs) showed activated B cell subsets and increased PD1 and TIM3 expression on T cells, along with a decreased subset of central memory CD4+ T cells​​.

In summary, the study underscores the complexity of long COVID, highlighting a variety of potential immunological mechanisms that contribute to its pathogenesis. These insights are crucial for understanding long COVID and developing targeted therapeutic strategies.

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