Preprint Club
A cross-institutional Journal Club Initiative

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.

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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.

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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?

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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.