Autoantibodies against type I IFNs in Lebanese patients hospitalized with COVID-19. – AAILC

Since 2003, three coronaviruses, SARS, MERS, and SARS-CoV-2, have led to devastating pandemics. Although vaccines are available, new variants and even new coronaviruses could emerge at any time. Understanding the molecular and cellular basis of human protective immunity against SARS-CoV-2 is critical. We recently discovered that inborn errors of type I interferons (IFNs) can underlie critical COVID-19 pneumonia, while over 10% of the life-threatening COVID-19 cases are caused by autoantibodies (auto-Abs) against type I IFNs, especially in elderly men. We started a collaboration between Paris and Beyrouth 6 months ago. We hypothesize that at least 10% of life-threatening COVID-19 cases in Lebanon are caused by auto-Abs against type I IFN. We propose to evaluate the prevalence of anti-IFN auto-Abs in Lebanese patients hospitalized for COVID-19, and investigate the epidemiological characteristics, as well as the immunological, and genetic mechanisms at play in patients with auto-Abs against type I IFN. Our immediate goal is to identify high risk patients quickly in Lebanon, which will create a precious window time for early treatment by IFN-ß which is not affected by viral variants, as well as prioritize them for vaccination. Our long-term goal is to better understand the disease mechanisms and provide strategies to prevent severe cases. Our project is supported by strong preliminary data. We have observed enrichment of auto-Ab positive patients with severe COVID-19 age between 20-30 and over 60 years old. More importantly, our project is built on strong collaboration between the Lebanese and French teams and supported by the international consortium COVID Human Genetic Effort (CHGE).