Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b-Literature Review and Personal Preliminary Experience.

Aurélien Mary,Myriam Eckes,Thierry Porée,Lucie Hénaut,Pierre Yves Macq,Louise Badoux,Michel Brazier,Hervé Dupont,Arnaud Cappe

doi:10.3389/fphar.2020.592543

Abstract

The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7–16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.

Highlights

The emergence of SARS-CoV-2 and the resulting COVID-19 pandemic has caused the most serious health crisis of this century
SARS-CoV-2 is responsible for respiratory disease which frequently leads to severe forms of pneumonia and acute respiratory distress syndromes (ARDS) (Zhu et al, 2020)
Beyond the viral infection per se, accumulating evidence suggests that a subgroup of patients with severe COVID-19 develop a severe inflammatory syndrome characterized by a dramatic rise of circulating pro-inflammatory cytokines IFN-γ, TNF-α, IL-6, IL-1 (Yang A.-P. et al, 2020; Yang L. et al, 2020) that attack cells in the pulmonary alveoli (Bradley et al, 2020; Carsana et al, 2020)

Summary

INTRODUCTION

The emergence of SARS-CoV-2 and the resulting COVID-19 pandemic has caused the most serious health crisis of this century. The dramatic pulmonary SARS-CoV-2 invasion observed in deceased COVID-19 patients (Bradley et al, 2020; Hanley et al, 2020), reinforces the hypothesis that the disease severity is associated with an immune system failure to clear the virus In line with this hypothesis it has been shown that the response to type I IFNs is impaired in subgroups of patients at high risk of mortality from COVID-19. Given the therapeutic rationale for IFN-β-1b aerosol, and the first results in favor of an acceptable particle size for local deposition in the lungs, an intervention consisting in the inhalation of IFN-β-1b for the treatment of four patients with a severe form of COVID19 was suggested by the clinical pharmacist to the intensive care unit team.

DISCUSSION

Findings

ETHICS STATEMENT