Introduction: Systemic lupus erythematosus (SLE) is associated with infection-related morbidity. The risk of adverse outcomes secondary to infections was exacerbated during the recent COVID-19 pandemic, prompting mass vaccination with the novel mRNA-based and viral-vectored vaccines. Limited data exist on the long-term impact of vaccination in patients with SLE. Methods: A post-vaccine group (PVG, n = 284) from a multicentric cohort of vaccinated patients with SLE from six tertiary referral centres in Northen Italy was compared with a control group (CG, n = 223) of similar demographics observed in the 2015–2019 period to investigate survival, hospitalisation, pregnancy, disease flare, disease progression, infection, and chronic complication accrual rates. Results: We did not observe excess SLE flares, SLE progression, hospitalisation, or pregnancy complications in the PVG. Cardiovascular complications due to comorbidities or to SLE were lower in the PVG than in the CG. Infections were more frequent in the PVG, related to COVID-19 in half of the cases, and were associated with SLE flares. Conclusions: Taken together, these data indicate that anti-COVID-19 vaccines are safe in the long-term when administered to patients with SLE. Stable, non-null rates of chronic comorbidity accrual and hospitalisation point out the existence of persistently unmet needs in patients with SLE.
