Researchers pinpoint major factor contributing to COVID-19 fatalities
COVID-19 can take a turn for the worse in some individuals, thanks to disruptions in the body's immune system as reported by scientists at Rockefeller University, USA. According to a study published in the journal Science, these complications are often due to a flawed response from the immune system, as explained by Almaty.tv referencing Lenta.ru.
The researchers found that approximately 3.5% of patients with severe COVID-19 have genetic mutations affecting their antiviral defense system. Moreover, about 10% of these patients with severe symptoms produce "auto-antibodies" that target their own immune system. Interestingly, the majority of affected patients are men, accounting for 94% of the cases.
These auto-antibodies seem to damage the production of antiviral interferons, a crucial component in the body's fight against viral infections. Without adequate interferons, the body struggles to combat the virus. In many instances, these interferons are rendered ineffective by these very auto-antibodies, mimicking autoimmune diseases such as rheumatoid arthritis or type 1 diabetes.
Scientists have identified that such auto-antibodies are not present in patients with mild COVID-19. For more in-depth insights, we can turn to the world of auto-antibodies and immune dysregulation in COVID-19 severity.
Auto-antibodies and Immune Dysregulation in COVID-19 SeverityAuto-antibodies, particularly anti-cytokine autoantibodies (such as against type I interferons), play a significant role in COVID-19 severity. These autoantibodies neutralize critical immune signaling molecules, impairing early viral clearance. This deficiency leaves individuals, especially men, susceptible to uncontrolled viral replication and hyperinflammation.
Sex-Specific Immune ResponsesMen exhibit reduced circulating follicular regulatory T cells (cTfr), which typically suppress excessive antibody production. The absence of these regulatory T cells in men coincides with a male-associated cellular network (T-peripheral helper cells, plasma blasts, and atypical B cells) that induces heightened neutralizing antibody responses. However, this heightened production can also lead to autoantibody generation, worsening outcomes due to autoimmunity and tissue damage.
Mechanistic Insights1. Early Phase: Anti-type I IFN autoantibodies hamper innate antiviral defenses, allowing unchecked SARS-CoV-2 replication.2. Late Phase: Persistent viral antigens sustain immune activation, leading to extrafollicular B-cell responses that bypass regulatory checkpoints, amplifying autoantibody production.3. Sex Disparity: The male-biased decline in cTfr disrupts immune homeostasis, exacerbating antibody-driven inflammation and organ injury.
Clinical ImplicationsThe relationship between autoantibody-mediated immune suppression (such as IFN deficiency) and dysregulated antibody networks explains higher COVID-19 severity in men, linking humoral hyperactivity to both protective and pathogenic outcomes.
- Auto-antibodies, specifically anti-cytokine autoantibodies, are significant contributors to the severity of COVID-19, particularly those against type I interferons, as they neutralize critical immune signaling molecules, hindering early viral clearance.
- Men with COVID-19 often exhibit reduced circulating follicular regulatory T cells (cTfr), typically responsible for suppressing excessive antibody production.
- The absence of these regulatory T cells in men coincides with a male-associated cellular network that induces heightened neutralizing antibody responses, which can lead to autoantibody generation, worsening outcomes due to autoimmunity and tissue damage.
- In the early phase of COVID-19, anti-type I IFN autoantibodies impair innate antiviral defenses, allowing unchecked SARS-CoV-2 replication.
- During the late phase of COVID-19, persistent viral antigens activate the immune system, leading to extrafollicular B-cell responses bypassing regulatory checkpoints, amplifying autoantibody production, and potentially exacerbating chronic medical conditions such as autoimmune diseases and other chronic diseases, which may negatively impact health-and-wellness.
