Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19

Am J Respir Crit Care Med. 2023 Jan 1;207(1):38-49. doi: 10.1164/rccm.202201-0011OC.


Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.

Keywords: COVID-19; autoimmunity; immunoglobulin A; pulmonary surfactant; pulmonary-associated surfactant protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies
  • Bronchoalveolar Lavage Fluid / chemistry
  • COVID-19*
  • Humans
  • Immunoglobulin A
  • Pulmonary Surfactants* / metabolism
  • Surface-Active Agents


  • Pulmonary Surfactants
  • Surface-Active Agents
  • Autoantibodies
  • Immunoglobulin A