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Objectives: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). Methods: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study—"The ReumaCoV Brazil"—designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). Results: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post–COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04–5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12–96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10–16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97–15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12–0.88], p = 0.02). Conclusion: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19. [ABSTRACT FROM AUTHOR]