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

TitlePlasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia.
Publication TypeJournal Article
Year of Publication2021
Authorsde Prost, N, Bastard, P, Arrestier, R, Fourati, S, Mahévas, M, Burrel, S, Dorgham, K, Gorochov, G, Tandjaoui-Lambiotte, Y, Azzaoui, I, Fernandes, I, Combes, A, Casanova, J-L, Mekontso-Dessap, A, Luyt, C-E
JournalJ Clin Immunol
Date Published2021 04
KeywordsAdult, Aged, Autoantibodies, COVID-19, Female, Humans, Interferon Type I, Male, Plasma Exchange, Prospective Studies, SARS-CoV-2

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.

Alternate JournalJ Clin Immunol
PubMed ID33616813
PubMed Central IDPMC7899072
Grant ListR01 AI088364 / AI / NIAID NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States