Researchers discover possible mechanism for poor oxygenation in severe COVID-19
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Researchers observed immunoglobulin A autoantibodies that target lung surfactant proteins B and C in patients with severe COVID-19, according to study results published in American Journal of Respiratory Medicine and Critical Care.
Further, the presence of these autoantibodies in lung surfactant may be a factor in alveolar collapse and poor oxygenation in patients with COVID-19, according to researchers.
“We identified [surfactant protein (SP)-B and SP-C immunoglobulin (Ig) A] in patients with severe COVID-19 and demonstrated that auto-IgAs impair the capability of pulmonary surfactant to lower surface tension,” Tobias Sinnberg, PhD, of the department of dermatology at University Hospital Tübingen, and colleagues wrote. “Our data further strengthen the notion that IgA antibodies against self-antigens in the lung corrupt crucial components of alveolar gas exchange, thereby providing novel mechanistic insights into the progression of COVID-19.”
In a multicenter cross-sectional study, Sinnberg and colleagues analyzed 147 blood samples, nine lung tissue samples and 36 bronchoalveolar lavage (BAL) fluid samples from patients treated at three Swiss hospitals and one German tertiary hospital to determine if IgA autoantibodies target lung-specific proteins and play a part in COVID-19 severity.
Researchers used enzyme-linked immunosorbent assays on blood samples, immunofluorescence staining on tissue samples and immunoprecipitations and mass spectrometry on BAL fluid samples to identify IgA autoantibodies and evaluate their impact on lung surfactant. They also took surface tension measurements with medical surfactant.
In the BAL fluid samples, researchers found that significantly more patients with COVID-19 from a cohort of 18 patients had IgA autoantibodies bound to pulmonary SP-B compared with a cohort of 18 patients without COVID-19 (50% vs. 17%; P = .03).
Researchers found no IgA when assessing tissue samples from patients who died of influenza (n = 2) or without any viral infection (n = 3), but observed that COVID-19 patients (n = 4) had SP-B IgA in the alveoli and SP-C IgA in lung tissue.
When incubating poractant alfa with plasma from 15 patients with severe COVID-19, researchers found that pulmonary surfactant significantly raised surface tension compared with using plasma from five patients with mild COVID-19 and five healthy controls.
With these observations, Sinnberg and colleagues suggested that auto-IgA potentially worsens COVID-19-related lung injury because it impacts lung surfactant function.
“Our data reveal a potential mechanistic driver of disease, as we show that auto-IgA interferes with the ability of pulmonary surfactant to lower surface tension,” Sinnberg and colleagues wrote. “This could lead to impaired stabilization of the pulmonary air sacs, thus contributing to alveolar collapse and insufficient oxygen exchange.”
Findings from this study by Sinnberg and colleagues spark new ideas for future studies that revolve around developing a better understanding of IgA, according to an accompanying editorial by Bradley W. Richmond, MD, PhD, assistant professor in medicine in the division of allergy, pulmonary and critical care medicine at Vanderbilt University Medical Center, and Charles S. Dela Cruz, MD, PhD, associate professor of medicine and of microbial pathogenesis at Yale School of Medicine.
“Follow-up studies investigating the IgA autoantibody response to multiple SARS-CoV-2 variants might improve our understanding of the peptide motifs driving autoantibody formation and explain differing degrees of lung pathogenicity among variants,” Richmond and Dela Cruz wrote. “At the bedside, future studies might examine whether response to corticosteroids differs on the basis of IgA autoantibody titers, allowing more targeted patient selection.
“Finally, development of chronic symptoms after COVID-19 (eg, ‘long COVID-19’) is an emerging public health issue,” they added. “IgA autoantibodies have been described in patients with autoimmune disease, providing a rationale for examination of IgA autoantibodies in patients with long COVID-19.”