Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia

Abstract

Purpose To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. Methods Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. Results Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. Conclusions PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-00994-9.

Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1

“…Therefore, it appears intuitive that interference with these cytokines results in a worsened outcome of SARS-CoV-2 infection. Strikingly, all individuals with high titers of pre-existing and neutralizing autoantibodies against type-I-IFNs, yet mild COVID-19 in our study were young females (13,14,22 and 25 y/a), whereas a pronounced excess of males older than 65 y/a was noted among most patients with autoantibodies against type-I-IFNs and severe COVID-19 (11). We are not able to verify to what extent autoantibodies against IFN-α and IFN-ω block the respective IFNs in our patients in vivo.…”

“…Autoantibodies against type-I-IFNs were reported in patients with severe COVID-19 (11), among whom a strong bias towards males (95%) and patients elder than 65 y/a (>50%) was also noted (11). Autoantibodies against type-I-IFNs in severe COVID-19 were confirmed in additional cohorts (14)(15)(16)(17). However, to date only cohorts collected for severe COVID-19 had been analysed (11,(15)(16)(17)(18).…”

Endomembrane targeting of human OAS1 p46 augments antiviral activity

“…Perturbations in any of these genes could affect OAS1 expression and its effector activity. Genetic studies, SARS-CoV-2 antagonism of IFN transcription, and autoantibodies against IFN/ strongly associate with severe COVID-19, indicating that the type I IFN pathway might be compromised in patients with severe COVID-19 (Bastard et al, 2021;de Prost et al, 2021;Pairo-Castineira et al, 2021;Xia et al, 2020). While it would be interesting to study the individual and combined effects of the above genes on OAS1 and COVID-19 disease, our study suggests there are strong selective pressures, presumably viral, impacting the prevalence of OAS1 causal splice site-SNP in in human populations.…”

Interferon-β Therapy in a Patient with Incontinentia Pigmenti and Autoantibodies against Type I IFNs Infected with SARS-CoV-2

“…Plasmapheresis was recently reported to decrease the titers of blood auto-Abs in hospitalized patients with critical pneumonia [4]. However, this invasive procedure cannot be proposed in the outpatient setting, before the development of severe pneumonia.…”