Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses
The review titled “Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses” provides a comprehensive analysis of the immune response to coronaviruses, particularly focusing on how the immune system’s reaction can contribute to the severity of diseases like COVID-19.
Here is a detailed summary:
- Scope: The study discusses the spectrum of diseases caused by human coronaviruses, ranging from mild colds to severe conditions like acute respiratory distress syndrome and death. It focuses on three highly pathogenic coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2.
- Key Points: The review underscores that severe diseases associated with these viruses are often a result of both the body’s dysregulated immune response and the active interference by the viruses themselves. This includes impaired induction of interferons, excessive inflammatory responses, and delayed adaptive immunity.
- Role of Interferons: Interferons, which are antiviral cytokines, play a crucial role in containing and clearing viral infections. However, their effectiveness can vary, with some studies showing that dysregulated interferon responses can lead to worse disease outcomes.
- Challenges: The timing and nature of interferon responses are critical and can differ among individuals, contributing to varying clinical outcomes. Inconsistent results in clinical trials have highlighted the complexity of using interferons as therapeutic options.
Viral Protein Antagonism
- Interferon Sensitivity and Antagonism: Different coronaviruses exhibit variable sensitivity to interferon. For example, MERS-CoV and SARS-CoV-2 are more sensitive to interferon than SARS-CoV and are better at inhibiting interferon induction and signaling.
- Innate Inflammatory Reaction: The initial response to coronavirus infection involves a rapid recruitment of immune cells and the release of pro-inflammatory mediators like IL-1β, IL-6, IL-8, and TNF. This response is crucial for pathogen clearance but can lead to immunopathological changes if uncontrolled.
- Role in Disease: The complement system, vital for pathogen elimination, can also contribute to severe disease when its activation is unchecked. It’s considered a key factor in conditions like endotheliitis and thrombosis in COVID-19.
- Importance in Virus Clearance: Adaptive immunity, including coronavirus-specific T cells and B cells, is essential for clearing the virus. In murine models, immunization with dendritic cells pulsed with SARS-CoV peptides has shown to protect against lethal challenges. However, severe COVID-19 is associated with dysregulation in this immune response.
T Cell-Mediated Pathogenesis
- Protective and Pathogenic Roles: While T cells play a protective role in coronavirus infections, they can also contribute to pathogenesis. For example, in murine coronavirus infections, depletion of T cells reduced lung pathology. In COVID-19 patients, a subset of T cells secreting high levels of inflammatory cytokines correlated with disease severity.
- Antibody Response Variability: Coronavirus infections induce both neutralizing and non-neutralizing antibodies. The response kinetics differ between patients with severe and mild diseases. High levels of virus-specific antibodies are seen in patients with severe disease, but these levels wane over time, especially in patients with mild disease. Despite this, SARS-CoV-2-specific memory B cells and long-lived plasma cells have been detected in convalescent patients, suggesting ongoing immune memory.
This review highlights the complex interplay between the immune system and coronaviruses, emphasizing the balance between effective viral clearance and the prevention of immune-mediated pathology. It underscores the need for a deeper understanding of these interactions to develop effective treatments and manage the immune response in patients with coronavirus infections.