Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19.

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 bronchoalveolar lavage 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 bronchoalveolar lavage 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 against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.

The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.