AUTHOR=Faguer Stanislas , Del Bello Arnaud , Danet Chloé , Renaudineau Yves , Izopet Jacques , Kamar Nassim 

TITLE=Apolipoprotein-A-I for severe COVID-19-induced hyperinflammatory states: A prospective case study

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.936659

DOI=10.3389/fphar.2022.936659

ISSN=1663-9812

ABSTRACT=Viral infections can promote cytokine storm and multiorgan failure in individuals with
underlying immunosuppression or specific genetic background. Hyperinflammatory states,
including critical forms of COVID-19, are characterized by a remodeling of lipide profile
including dramatic decrease of the serum levels of apolipoprotein-A-I (ApoA-I), a protein
known for its capacity to reduce systemic and lung inflammation, modulate innate and
adaptative immunity and prevent endothelial dysfunction and blood coagulation. In this study,
four immunocompromised patients with severe COVID-19 cytokine storm that progressed
despite standard-of-care therapy (omicron (n=3) and delta (n=1) variants) received 2 to 4
infusions (10 mg/kg) of CER-001 an ApoA-I-containing HDL mimetic. Injections were well
tolerated with no serious adverse events. Three patients treated while not on mechanical
ventilation had early clinical and biological improvement (oxygen withdrawal and correction
of hematological and inflammatory parameters, including serum levels of interleukine-8) and
were discharged from the hospital 3 to 4 days after CER-001 infusions. In the fourth patient
who received CER-001 after orotracheal intubation for acute respiratory distress syndrome,
infusions were followed by transient respiratory improvement before secondary worsening
related to ventilation-associated pneumoniae. This pilot uncontrolled exploratory
compassionate study provides initial safety and proof-of-concept data from patients with
COVID-19 cytokine storm receiving ApoA-I. Further randomized controlled trial evaluation is
now required to ascertain whether ApoA-I has any beneficial effects in patients with COVID19
cytokine storm.