Type 2 Diabetes Mellitus Aggravates Complement Dysregulation and Affects Cortisol Response in Patients with Post-COVID-19

Wenrui Ji,1,* Xiaomin Xie,1,* Guirong Bai,1 Yalei Fan,2 Yanting He,1 Li Zhang,1 Haiyan Zhou,1 Ling Li,1 Dan Qiang,1 Huan Li1 1Department of Endocrinology, the First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China; 2The Second Clinical Medical School of Ningxia Medical University, Yinchuan, 750001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomin Xie, Department of Endocrinology, the First People’s Hospital of Yinchuan, Liqun West Street No. 2, Xingqing District, Yinchuan, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Tel +8613895189599, Email [email protected]: COVID-19 viral infection results in dysregulation of the complement system and a decrease in cortisol and adrenocorticotropin hormone (ACTH) levels. This study aimed to explore the complement system, as well as cortisol and ACTH responses in patients with post-COVID-19 conditions (PCC) and type 2 diabetes mellitus (T2DM).Patients and Methods: This study recruited 31 patients with PCC and T2DM (PCC-T2DM), 19 patients with PCC (PCC), 10 patients with T2DM (T2DM), and 10 healthy participants (control). Cortisol and ACTH in the PCC and PCC-T2DM groups were assessed using the insulin tolerance test. In the fasting state, serum samples were collected for proteomic analyses. Spearman correlation analysis was performed between proteins and cortisol, as well as between proteins and ACTH.Results: Cortisol and ACTH levels were consistently decreased in the PCC and PCC-T2DM groups. Proteomic analyses revealed that most of the differentially abundant proteins (DAPs) in the PCC vs control and PCC-T2DM vs T2DM were involved in the coagulation and complement cascade, and the essential complement C3 was significantly upregulated in the PCC and PCC-T2DM groups when compared to their controls. Additionally, complement-related DAPs in the PCC vs control and PCC-T2DM vs T2DM were significantly correlated with cortisol and ACTH levels. In comparing PCC-T2DM samples with PCC samples, we found that upregulated DAPs were linked to the complement system and other immune system, and most DAPs were negatively correlated with cortisol and ACTH.Conclusion: Our study revealed that T2DM exacerbated dysregulation of the complement system in patients with PCC, and significant correlations were present between complement protein levels and those of cortisol and ACTH. These results provide novel insights into the dysregulation of complement and endocrine hormones in patients with PCC and T2DM.Keywords: post-COVID-19 condition, type 2 diabetes mellitus, complement, cortisol, adrenocorticotropin hormone