IgM autoantibodies recognizing ACE2 are associated with severe COVID-19

Area of Science:

• Immunology
• Pathology
• Virology

Background:

• Severe COVID-19 pathogenesis involves unclear mechanisms.
• Understanding SARS-CoV-2 immune responses is critical.

Approach:

• Investigated autoantibodies in severe COVID-19 patients.
• Analyzed antibody class-switching, complement activation, and lung pathology.
• Correlated autoantibodies with disease severity and clinical presentation.

Key Points:

• Robust IgM autoantibodies against angiotensin converting enzyme-2 (ACE2) found in 27% of severe COVID-19 patients.
• These antibodies are rare in non-ventilated hospitalized patients (3.8%).
• IgM autoantibodies activate complement and show endothelial cell staining in lung vasculature.

Conclusions:

• Autoantibodies targeting vascular ACE2 may drive angiocentric pathology in severe COVID-19.
• Findings suggest potential predictive biomarkers and therapeutic targets for severe SARS-CoV-2.
• The T-independent nature of this antibody response warrants further investigation.