2021-Jan-Wang | My Site

Diverse Functional Autoantibodies in Patients with COVID-19

Wang et al. (MedRxiv) DOI: 10.1101/2020.12.10.20247205

Keywords

COVID-19
Autoantibodies
Humoral Immunity

Main Findings

By developing a novel high-throughput assay to measure a range of 2,770 extracellular and secreted proteins, Wang and colleagues determined the full breadth of autoantibody reactivity in COVID-19 and their association with immunological and clinical outcomes by studying 194 subjects (Yale patients and healthcare workers) with a wide range of disease severity, including 30 seronegative controls.
The authors demonstrated that autoantibody prevalence was predominant in severe COVID-19 patients, particularly antibodies against the Interferon signalling pathway; thus validating and extending previously reported studies (Bastard et al., Cell, 2020).
Autoantibodies against cytokines - IFN-I, GM-CSF, CXCL1, CXCL7 - and cellular targets - B cell, T cells and monocyte surface proteins - had potent functional activities as they were directly correlated with various virological, immunological, and clinical parameters in vivo within COVID-19 patient samples.
Further, murine surrogates of autoantibodies against IFNAR and IL-18 led to increased disease severity in a mouse model of SARS-CoV-2 infection.
Longitudinal analysis of autoantibodies on a subset of patients indicates different kinetic profiles, suggesting their potential contribution in the long term.

Limitations

So far, the authors could not detect COVID-19 specific antibodies that could be used as biomarkers of disease severity; highlighting the need for more extensive cross-sectional and longitudinal studies.

Significance/Novelty

The authors have developed a novel high-throughput assay that aims to measure the "exoproteosome" with good sensitivity. This assay can be applied to other disease contexts.
They showed the surprising extent of autoantibody reactivities in patients with COVID-19, which suggests humoral immunopathology (and it's regulation) as an intrinsic aspect of disease pathogenesis.
Patients with pre-existing autoantibodies may be at heightened risk of severe disease due to autoantibody-mediated deficiencies in immune responses during early SARS-CoV-2 infection.
This work leads to outstanding questions in the field - How long do these autoantibodies last? What damage do they cause? How are they induced? Are they associated with Post-COVID-Syndrome?

Credit

Reviewed by Isabela Pedroza-Pacheco as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford. Follow her on Twitter.