A collaboration between the Penninger labs at UBC and IMBA in Austria with Swiss researchers has found that patients with severe COVID-19 mount IgA antibodies against pulmonary surfactant proteins, blocking their function and potentially contributing to the collapse of alveolae and poor oxygenation.
The researchers did not see these autoantibodies in the in lungs of patients with other respiratory infections, such as severe influenza. The auto-IgAs seem to be a COVID-19 specific phenomenon, which is also detectable in the blood of severe COVID-19 patients. The implications of this presence is currently unknown.
“COVID-19 is a disease that is associated with various autoimmune phenomena,” said co-first author Dr. Omar Ali Hasan, a postdoctoral fellow in the Penninger lab, in an email exchange. “We wanted to explore whether there are autoantibodies directed against proteins that are found in the lungs of severe COVID-19 patients, as the lungs stand at the center of the disease.
“We discovered that patients with severe COVID-19 develop IgA-type autoantibodies that bind to lung surfactant proteins,” added Ali Hasan. “Lung surfactant is a mix of lipids and proteins found in the air sacs of our lungs. It is essential for reducing the lung’s surface tension. If surfactant is impaired, breathing and oxygen exchange become difficult. Importantly, we saw that these auto-IgAs seem to interfere with the surfactant protein function.”
Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness, according to the numerous peer-reviewed publications. This makes predicting the percentage of severe cases, and/or likelihood of severity challenging.
The Q&A below is based on “Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19“
What is the role of autoimmunity in severe COVID-19 and your discovery?
Several studies have reported autoimmune phenomena in patients with COVID-19, such as Guillan-Barré-Syndrome and Type 1 diabetes. How and why some patients develop them while others do not, remains unclear. In 2020, we discovered that many patients with severe COVID-19 harbored antiphospholipid auto-IgA in their blood, which can lead to blood clots. Clinically, many patients with severe COVID-19 develop thromboses in several organs and these auto-IgAs may be an additional factor for their development.
Explain what is happening in patients with surfactant protein. First, define what that is, and then explain.
Severe COVID-19 patients have IgAs directed against surfactant proteins B and C. Using surface tension experiments, we were able to show that serum from these patients interferes with the protein function. Previous reports show molecular similarities between certain parts of the SARS-CoV-2 spike protein and these lung surfactant proteins. It is possible that some IgAs that are directed against the virus erroneously attack these proteins. However, the exact mechanism as to how they disrupt the protein function remains unclear.
How did UBC’s research contribute?
Dr. Josef Penninger, the director of the Life Sciences Institute (LSI), provided expertise and critical input for expanding our rationale and for our design of the experimental pipeline. Also, some experiments were reproduced in our lab at the LSI.
How did reach your conclusions?
Arriving at our conclusions was a step-by-step process that involved experts from pneumonology, pathology, immunology, dermatology, internal medicine, and basic biology which were all part of a large international collaborative effort.
Are doctors changing how they are treating patients because of these findings? Where, and how?
The Swiss Society for Infectious Diseases (SSI) now cites us as one of their reference papers for administering inhaled corticosteroids early on during disease (see French version: https://ssi.guidelines.ch/guideline/3934/fr). Also, two clinical studies investigating the use of bronchoscopically applied surfactant in patients with severe COVID-19 found that treatment was associated with reduced 28-day mortality and earlier dismissal from hospital. We are definitely excited to see how a focus on surfactant could contribute to a better outcome.
As well, the American Journal of Respiratory and Critical Care Medicine published an editorial about our paper in August 2022, which is an interesting read: https://www.atsjournals.org/doi/10.1164/rccm.202208-1549ED