Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical University, No. 1 Xue-Yuan Rd., University Town, Fuzhou, 350122, Fujian, China.
Xiamen Key Laboratory of Marine Functional Food, College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, Fujian, China.
J Transl Med. 2024 Jan 23;22(1):94. doi: 10.1186/s12967-024-04887-4.
Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity.
We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms.
With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4 T, CD8 T and the ratio of CD4/CD8 T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells.
Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.
过敏疾病（ADs）如哮喘被认为是 COVID-19 感染的风险因素。然而，最近的观察性研究表明，这种假设的相关性相互矛盾。因此，我们系统地研究了各种 ADs 与 COVID-19 感染/严重程度之间的遗传因果关系。
我们对五种类型的 ADs 和最新一轮 COVID-19 GWAS 荟萃分析数据集（危重症、住院和感染病例）进行了两样本双向 Mendelian 随机化（MR）研究。我们还进一步验证了显著的因果关联，并阐明了潜在的潜在分子机制。
使用最合适的 MR 方法，哮喘对 COVID-19 危重症和住院病例始终表现出因果保护作用（OR < 0.93，p < 2.01 × 10），这一结果在另一个经过验证的 GWAS 数据集（OR < 0.92，p < 4.22 × 10）中得到了进一步证实。此外，我们的 MR 分析还观察到虾过敏等食物过敏与 COVID-19 感染/严重程度风险之间存在显著的因果关联。然而，我们没有发现 COVID-19 表型对 ADs 风险的任何显著因果影响。关于潜在的分子机制，不仅包括 CD4 T、CD8 T 和 CD4/CD8 T 细胞比例在内的多种免疫相关细胞对 COVID-19 表型和各种 ADs 表现出显著的因果作用，血液学特征包括单核细胞也与它们显著相关。相反，哮喘和虾过敏等各种 ADs 可能通过影响多种血液学特征和免疫相关细胞与 COVID-19 感染/严重程度呈因果关系。
我们的系统和双向 MR 分析表明，各种 ADs，特别是哮喘对 COVID-19 感染/严重程度存在单向因果作用，但反之则不然。因果作用的潜在分子机制需要更多关注血液细胞/特征的临床监测，并可能有助于为感染 COVID-19 的过敏患者开发有效的治疗策略。
