Anti-SARS-CoV-2 Nucleoprotein IgA is Associated with Worse Disease Severity in Critically Ill COVID-19 Pneumonia Patients

Authors

• David Brett-Major, University of Nebraska Medical CenterFollow
• Dylan S. George, University of Nebraska Medical CenterFollow
• Eric D. Morrell, University of Washington Medical Center
• Carmen Mikacenic, Virginia Mason Franciscan Health
• Julie Carstens, University of Nebraska Medical CenterFollow
• Laura E. Evans, University of Washington Medical Center
• Mark M. Wurfel, University of Washington Medical Center
• Pavan K. Bhatraju, University of Washington Medical Center
• M. Jana Broadhurst, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Frontiers in Immunology

Publication Date

2026

Volume

17

Abstract

While humoral responses to vaccination and infection have largely focused on IgG, there is an evolving literature on ways in which IgA may drive neutrophil activity in lung injury secondary to viral infections, including COVID-19. We evaluated 238 immune-naïve, critically ill patients in the first year of the COVID-19 pandemic. Employing a laboratory-developed, multiplexed antibody testing, clinical history, medical record, and machine learning, we pursued relationships between systemic IgA and disease severity. Individuals with elevated anti-N IgA had 4-fold odds of more severe disease. This work emphasizes the importance of continued work to understand how different elements of the immune system participate together in contributing to patient outcomes.

MeSH Headings

Humans, COVID-19, Critical Illness, Immunoglobulin A, Severity of Illness Index, SARS-CoV-2, Antibodies, Viral, Female, Male, Middle Aged, Aged, Neutrophils, Coronavirus Nucleocapsid Proteins, Phosphoproteins

DOI Link

10.3389/fimmu.2026.1870217

ISSN

1664-3224

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Brett-Major, David; George, Dylan S.; Morrell, Eric D.; Mikacenic, Carmen; Carstens, Julie; Evans, Laura E.; Wurfel, Mark M.; Bhatraju, Pavan K.; and Broadhurst, M. Jana, "Anti-SARS-CoV-2 Nucleoprotein IgA is Associated with Worse Disease Severity in Critically Ill COVID-19 Pneumonia Patients" (2026). Journal Articles: Epidemiology. 235.
https://digitalcommons.unmc.edu/coph_epidem_articles/235