Published in:
01-10-2021 | SARS-CoV-2 | Commentary
Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β
Authors:
Donald C. Vinh, Laurent Abel, Paul Bastard, Matthew P. Cheng, Antonio Condino-Neto, Peter K. Gregersen, Filomeen Haerynck, Maria-Pia Cicalese, David Hagin, Pere Soler-Palacín, Anna M. Planas, Aurora Pujol, Luigi D. Notarangelo, Qian Zhang, Helen C. Su, Jean-Laurent Casanova, Isabelle Meyts, On behalf of the COVID Human Genetic Effort
Published in:
Journal of Clinical Immunology
|
Issue 7/2021
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Excerpt
Since December 2019, over 150 million individuals have been infected with SARS-CoV-2 globally. While most cases (>95%) are asymptomatic or mild, a small proportion develop moderate, severe, or critical COVID-19 pneumonia requiring hospitalization, at times in the intensive care unit [
1]. At least 2 million patients have already died [
2]. The main epidemiological risk factor associated with critical pneumonia or death is age > 65 years; however, life-threatening COVID-19 has also affected younger people, albeit sporadically. Studies have suggested that type I interferon (IFN) immunity contributes to the control of SARS-CoV-2 infection [
3‐
8]. Notably, inborn errors of TLR3- and IRF7-dependent type I IFN production or amplification underlie severe disease in ~3% of a cohort of relatively young adult patients analyzed by the COVID Human Genetic Effort (
COVIDhge.com) [
3]. In at least an additional 10% of cases, high levels of pre-existing auto-antibodies (auto-Abs) neutralizing most type I IFNs, but rarely IFN-β, abrogate type I IFN–dependent control of SARS-CoV-2 replication in vitro, thereby underlying critical disease in vivo [
3,
4,
9,
10]. This observation was replicated in other cohorts [
11‐
15]. The mean age of patients with inborn errors was 48 years, while that of patients with auto-Abs was 65 years. These findings support a two-step model of COVID-19 pathogenesis: defective type I IFN immunity in the first hours and days of infection leads to uncontrolled viral replication with spread to the lungs and other tissues, with subsequent excessive leukocyte recruitment, underlying uncontrolled inflammation [
5]. This model of early deficient type I IFN function provides a framework for novel preventive and therapeutic approaches of COVID-19. Here, we explore two therapeutic routes that aim to restore protective type I IFN immunity: [
1] the early administration of IFN-β in ambulatory subjects, including exposed individuals prior to infection, pre-symptomatic infected individuals and symptomatic individuals, and [
2] the removal of auto-Abs to type I IFN in hospitalized patients. We also discuss the implications of these findings for other preventive and therapeutic interventions, including B cell depletion, JAK inhibitors, intravenous immunoglobulins, the use of convalescent plasma and virus-specific mAbs, and vaccination. This discussion is timely, as more than one year into the pandemic, we are still in the dark about the best prevention and treatment for severe COVID-19 pneumonia, while the emergence of more contagious viral variants, causing more severe disease, raises concerns regarding the efficacy of the nascent vaccination programs [
16,
17]. …
