To the Editor:
We have read with a great interest the study by Fernandez et al (1) published in a recent issue of Critical Care Medicine. In this case-series, the authors reported the outcome of four patients admitted in ICU with coronavirus disease 2019 (COVID-19) complicated with multiorgan failure and treated with a combination of plasma exchange (PE) and IV immunoglobulins added to antibiotherapy, antiviral, and steroïds.
After PE initiation, all the four patients presented a decrease in inflammatory biomarkers and none died in ICU. The authors hypothesized that the removal of inflammatory mediators from circulation was mainly responsible for the improvement.
We think that PE could effectively be a benefit for severe COVID-19 but not for the same reasons proposed by the authors. Recent studies had suggested that type 1 interferons (I-IFNs), one of the main antiviral immune systems, were impaired during life-threatening COVID-19 (2). If constitutional inborn errors were identified in 3.5% of patients admitted in ICU, the presence of IgG autoantibodies (Abs) against IFN-α2 and IFN-ω in 13.7% of a worldwide severe COVID-19 adult cohort was especially observed (3,4). These IgG auto-Abs, mostly observed in male gender, strongly neutralized type I-IFNs and blocked antiviral activity (4). In addition, only an important depletion of IgG auto-Abs allowed the restoration of a normal immune response (4).
We believe that, more than the clearance of proinflammatory mediators, PE with frozen fresh plasma has the advantage to combine both auto-Abs depletion and supplementation of type I-IFNs and could be interesting, in particular in male adults, which seems more at risk of autoimmunity.
1. Fernandez J, Gratacos-Ginès J, Olivas P, et al.; Covid Clinic Critical Care (CCCC) Group. Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection. Crit Care Med. 2020; 48:e1350–e1355
2. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369:718–724
3. Zhang Q, Bastard P, Liu Z, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020; 370:eabd4570
4. Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020; 370:eabd4585