Viral infection plays an important role in driving activity of autoimmune diseases. Preceding SARS-CoV-2 infection has been observed to trigger disease flares in systemic lupus erythematosus (SLE). Besides cytomegalovirus, SARS-CoV-2 can induce pulmonary capillaritis to develop diffuse alveolar hemorrhage (DAH), a respiratory emergency of SLE. Owing to lack of comprehensive studies for SARS-CoV-2-triggered DAH in SLE, we conducted a monocentric analysis with mechanistic investigation. Hospitalized SLE patients were retrospectively analyzed for the DAH manifestation in the COVID-19 era since December, 2019, focusing on those with preceding SARS-CoV-2 infection. Peripheral blood (PB) and lung tissues samples and immune/alveolus cell lines were used for mechanistic research. Twenty-five DAH episodes were identified in 21 SLE patients (3% occurrence), all in disease flares with high activity scores. During the domestic omicron variant outbreak, 7 patients (33%) had preceding SARS-CoV-2 infection, 3 to 7 weeks earlier to the onset of DAH, while they had elevated IL-6, nitro-oxidative stress- and cell death-associated molecules levels in PB and lung tissues with enhanced apoptosis formation. IL-6-stimulated alveolus/immune cells exhibited a dose-dependent increase in nitro-oxidative stress- and cell death-associated molecules levels, up-regulated p38MAPK/NF-κB-p65 phosphorylation, raised ROS expression and enhanced apoptosis formation. These findings implicated cell death induced by IL-6-activated nitro-oxidative stress to generate circulating immune complexes with pulmonary deposition as the mechanism for DAH preceded by SARS-CoV-2 infection in SLE. The DAH manifestation preceded by SARS-CoV-2 infection is observed in SLE with disease flares, requiring careful monitor and management of COVID-19 in such patients.
Weng et al. (Sun,) studied this question.