Compared with OPERA, similar covariates were associated with a higher risk of SIs in patients with PPMS in the univariate analysis (Supplemental Figure 6), including being located in the United States (2.40 [95% CI: 1.30–4.43]), having overweight or obesity (BMI > 25 kg/m2, 2.12 [95% CI: 1.39–3.22]), IgM < LLN (2.04 [95% CI: 1.46–2.85]), and the presence of ⩾2 comorbidities (2.60 [95% CI: 1.53–4.40]), of which renal and urinary, depression, cardiovascular comorbidities, and previous infections were the most significant in a descending order (Supplemental Figure 6). Here, CD40LG is linked to major depressive disorder.