• Tobias Sinnberg, Christa Lichtensteiger, Omar Hasan Ali, Oltin T Pop, Ann-Kristin Jochum, Lorenz Risch, Silvio D Brugger, Ana Velic, David Bomze, Philipp Kohler, Pietro Vernazza, Werner C Albrich, Christian R Kahlert, Marie-Therese Abdou, Nina Wyss, Kathrin Hofmeister, Heike Niessner, Carl Zinner, Mara Gilardi, Alexandar Tzankov, Martin Röcken, Alex Dulovic, Srikanth Mairpady Shambat, Natalia Ruetalo, Philipp K Buehler, Thomas C Scheier, Wolfram Jochum, Lukas Kern, Samuel Henz, Tino Schneider, Gabriela M Kuster, Maurin Lampart, Martin Siegemund, Roland Bingisser, Michael Schindler, Nicole Schneiderhan-Marra, Hubert Kalbacher, Kathy D McCoy, Werner Spengler, Martin H Brutsche, Boris Maček, Raphael Twerenbold, Josef M Penninger, Matthias S Matter, and Lukas Flatz.
• Department of Dermatology.
• Am. J. Respir. Crit. Care Med. 2023 Jan 1; 207 (1): 384938-49.

AbstractRationale: 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.

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