Allergic asthma and type-2 immunity reduce COVID-19 severity

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, resulting in millions of cases and deaths. As COVID-19 continues to circulate, the interplay between COVID-19 and other chronic diseases, particularly asthma, remains an important public health concern. Asthma, a heterogeneous disease affecting over 300 million people globally, is characterized by airway inflammation and hyper-reactivity. Asthma exacerbations are often triggered by respiratory infections, leading to an increased risk of pulmonary complications. Given that the COVID-19 pandemic has spurred significant debate on its relationship with asthma, understanding how different asthma phenotypes, particularly allergic versus non-allergic asthma, affect COVID-19 risk is critical. Using Mendelian randomization (MR), this study investigates the genetic determinants of asthma subtypes in relation to COVID-19 susceptibility and severity. Our findings reveal a complex relationship, with non-allergic asthma associated with increased COVID-19 risk, while allergic asthma, particularly when co-occurring with allergic rhinitis, correlates with reduced COVID-19 risk. Although COVID-19 and allergic asthma are independent clinical manifestations, the above results indicate the trade-off between allergic asthma and COVID-19 risk, implying a shared origin of allergic disease and allergic immune defense. As such, I proposed an alternative perspective for allergic diseases: the ability to mount an allergic immune defense can be protective in the face of infectious diseases such as COVID-19; however, when excessive and misguided to allergens, the allergic immune defense can result in allergic disease. Thus, the dramatic rise of allergic diseases during the past few decades might be caused by the survival advantage of allergic immune defenses, which increases the adaptation of the host to lethal infections and thus is favored in the evolutionary process of natural selection.