Interferon-\u03b12 Auto-antibodies in Convalescent Plasma Therapy for COVID-19

Matthijs P Raadsen,Henrik Endeman,Corine H Geurtsvankessel,Eric C M Van Gorp,Bart J A Rijnders,Marion P G Koopmans,Marco Goeijenbier,Mart M Lamers,Casper Rokx,Arvind Gharbharan,Johannes P C Van Den Akker,Bart L Haagmans,Anna Z Mykytyn,Carlijn C E Jordans,Petra B Van Den Doel

doi:10.1007/s10875-021-01168-3

Matthijs P Raadsen, Henrik Endeman + Show 13 more

Open Access

https://doi.org/10.1007/s10875-021-01168-3

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Abstract

PurposeTo study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment.MethodsSera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus–based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion.ResultsIFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract.ConclusionsIFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Highlights

SARS coronavirus 2 (SARS-CoV-2) causes both upper and lower respiratory tract infections in humans with a broad spectrum of disease severity, ranging from asymptomatic viral replication and shedding to life-threatening COVID-19
Summary This study compares the presence of interferon-α2 auto-antibodies in COVID-19 patients in the acute and convalescent phase, across multiple levels of disease severity, and ICU patients with other infectious respiratory diseases
Sera from blood plasma donors were taken at a mean of 51 (SD ± 14 days) days after COVID-19 disease onset

Summary

Introduction

SARS coronavirus 2 (SARS-CoV-2) causes both upper and lower respiratory tract infections in humans with a broad spectrum of disease severity, ranging from asymptomatic viral replication and shedding to life-threatening COVID-19. The latter is characterized by severe bilateral pneumonia resulting in acute hypoxia, systemic inflammation, and hypercoagulability [1, 2]. Auto-antibodies against type I IFNs (IFN-Abs) were found in approximately 10% of patients with life-threatening COVID-19, resulting in an auto-immune phenocopy of inborn errors of type I IFN signaling [6] These IFN-Abs were not found in mild cases and were rare in healthy individuals (~0.3%). Auto-Abs against IFN-α2 were found in 4/116 of convalescent blood plasma donors previously hospitalized with COVID-19, with 2 (1.5 %) neutralizing IFN α2 in a cell-based assay [7]

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