Proteomics Reveals That Vitamin D Deficiency Leadsto Immunoglobulin Abnormalities and Immune Dysregulation in Patientswith Post-COVID-19 Condition

Vitamin D (VD) levels are closely related to the occurrence of post-COVID-19 conditions (PCCs), but the specific mechanism is still unclear. Here, a total of 50 PCC patient serum samples were divided into the VD sufficient group (VD ≥ 30 ng/mL), the VD insufficient group (20 ng/mL ≤ VD < 30 ng/mL), and the VD deficiency group (VD < 20 ng/mL) and then subjected to proteomic analysis. We identified 15 differential abundance proteins (DAPs) between the VD sufficient and VD insufficient groups, including 5 immunoglobulin proteins (JCHAJN, IGHV4–28, GHV4–34, IGHM, and IGLV2–11), which were significantly negatively correlated with VD levels in PCC patients. These DAPs were primarily enriched in immune-related pathways such as the TNF signaling pathway and the B cell receptor signaling pathway. Compared with the VD insufficient group, VD deficiency resulted in 4 proteins being upregulated and 8 proteins being downregulated. The declined abundance of IGLV1–47 negatively correlated with serum VD levels. Albumin (ALB) was in the center of the protein–protein interaction (PPI) network map of all DAPs and was negatively correlated with serum VD levels. In conclusion, VD insufficiency/deficiency leads to abnormalities in immunoglobulin heavy, light, and J chains, resulting in PCC syndrome. VD supplementation may be a potential therapeutic strategy to alleviate the symptoms of PCC.