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

Abstract

Viral infections can promote cytokine storm and multiorgan failure in individuals with an underlying immunosuppression or specific genetic background. Hyperinflammatory states, including critical forms of COVID-19, are characterized by a remodeling of the lipid profile including a 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 adaptive 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– 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 interleukin-8) and were discharged from the hospital 3–4 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 pneumonia. This pilot uncontrolled exploratory compassionate study provides initial safety and proof-of-concept data from patients with a COVID-19 cytokine storm receiving ApoA-I. Further randomized controlled trial evaluation is now required to ascertain whether ApoA-I has any beneficial effects on patients with a COVID-19 cytokine storm.

Association of low HDL-c levels with severe symptoms and poor clinical prognosis in patients with severe fever and thrombocytopenia syndrome

“…Studies have indicated that Omega-3 polyunsaturated fatty acids (PUFA) can improve lipid metabolism by reducing triglyceride levels and increasing HDL levels, while also reducing inflammatory responses ( Ni et al, 2020 ). This approach has shown positive effects in the treatment of COVID-19 ( Sorokin et al, 2020 ; Faguer et al, 2022 ). Furthermore, the use of statins to increase HDL levels is also a current research focus in the context of COVID-19 ( Vahedian-Azimi et al, 2021 ).…”

The relationship between lactate dehydrogenase and Apolipoprotein A1 levels in patients with severe pneumonia

“…The rise in LDH expression in the serum of patients with pneumonia may be due to a more intense inflammatory response in the lungs, accompanied by hypoxia, causing myocardial damage [15] . ApoA1 is an inflammatory factor with anti-inflammatory, antioxidant, and cholesterol-reversing effects, and is one of the components of HDL, which exerts its anti-inflammatory effects by inhibiting the expression of inflammatory cytokines [16] [17] . ApoA1 is closely correlated with the progression of pneumonia disease, and decreased expression may cause an increase in the expression of pro-inflammatory factors, which in turn decreases the ability of lung tissue to resist pathogens and further exacerbates the inflammatory response [18] .…”

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

“…The effect of CER-001 as a salvage therapy was recently evaluated in four COVID-19 patients, three out of which showed a decline in cytokine storm and hence, recovery [ 290 ]. CER-001 administration also showed a significant reduction in HDL-SAA content, improving the native HDL–cargo characteristics [ 291 ].…”