CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

LC was associated with fungal translocation, gut dysfunction, and enhanced inflammation. The anti-inflammatory vitamins K2/D3 were previously shown to reduce inflammation and help attenuate the course of acute COVID infection. This trial aims to investigate the effects of Vitamins K2/D3 on LC symptoms, gut markers and inflammatory markers in people with established long COVID. Methods: This single-site randomized-controlled enrolled adults experiencing ≥2 moderate long COVID symptoms at least 3 months after COVID-19 infection. The RECOVER Long COVID index (JAMA 2023), number of LC symptoms, and resolution of symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI Vitamin D3 or standard of care (SOC) for 24 weeks. Co-primary endpoints were changes in symptomatology and in select inflammatory markers at 24 weeks. Results: We enrolled 151 participants (n=98 received vit K2/D3 and 53 standard of care). The median age was 46 years, 71% female and 29% non white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group had a sharp increase in 25(OH) D indicating good treatment adherence, without change in the control arm. Vitamins K2/D3 arm showed a 3.2 (P=0.04) reduction in LC Index (P=0.04) and nearly two less (∆ = -1.7; P=0.02) total number of LC symptoms compared to the SOC arm. Additionally, larger reductions in oxidized LDL, sTNF-RI, CD163, and the fungal translocation marker (1, 3)-β-d-glucan (BDG) were observed in the vitamins K2/ D3 arm compared to the SOC arm (P<0.01). In adjusted models, vitamins K2/ D3 randomization was associated with decreases in LC Index, but decreases in inflammatory markers and BDG were not. Decreases in BDG were associated with K2/D3 randomization and with decreases in inflammatory markers. Conclusions: Vitamins K2/D3 improved Long COVID Index, number of LC symptoms, fungal translocation and several inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long COVID. Larger and longer studies are needed to assess the impact of this safe anti-inflammatory strategy.

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Lipid Nanoparticles Targeting Neutrophil and NETs to Mitigate Lung Injury in SARS-CoV-2 Mice Juwon Park 1 , Haeun Shin 1 , Stefanos Giannakopoulos 1 , Joo Dong Park 2 , Chun Gwon Park 2 , Saguna Verma 1 , Wooram Park 2 1 University of Hawaii at Manoa, Honolulu, HI, USA, 2 Seoul National University, Seoul, South Korea Background: The need to understand key players driving pulmonary inflammation and fibrosis in COVID-19 patients leading to effective preventive strategies is imminent. Excessive neutrophil activation, including extracellular trap (NET) formation, is associated with severe COVID-19 and long-term pulmonary sequelae. However, the clinical applications of neutrophil-targeting therapies are challenging due to short bioavailability and lack of cell-type specificity. Methods: The lipid nanoparticle (LNP) platform designed to deliver two NET inhibitors, DNase I and Sivelestat (Siv), referred to as DPNLNPs, specifically to lung neutrophils. The LNP design was optimized by incorporating the cationic lipid into a conventional LNP formulation to enhance lung-specific delivery. To enable neutrophil targeting, Ly6G antibodies were cleaved into F(ab’)2 fragments and conjugated to the LNPs. We evaluated the therapeutic efficacy DPNLNP in the K18-hACE2 mouse model. Results: In vitro and in vivo experiments demonstrate that DPNLNPs preferentially accumulate in the lung neutrophils and degrade NETs as efficiently as the free DNase I and Siv. Additionally, administration of DPNLNPs in K18-hACE2 mice significantly inhibited SARS-CoV-2-induced NETs at a much lower dose than the free drugs and correlated with reduced lung and systemic inflammation, lung epithelium injury, and collagen deposition. Importantly, DPNLNP treatment only during the symptomatic phase of infection improved SARS-CoV-2 outcome revealing the complex role of NETs in COVID-19 pathogenesis. Conclusions: Together, this study serves as a proof-of-concept for adapting the LNP platform to deliver more than one immunomodulatory drug in a cell specific manner to manage NET-associated complications in COVID-19 and other respiratory diseases.

Poster Abstracts

337

Vitamins K 2 and D 3 Improve Long COVID Index, Fungal Translocation, and Inflammatory Biomarkers Ornina Atieh 1 , Jhony Baissary 1 , Jared C. Durieux 2 , Danielle Labbato 2 , Marc Abboud 3 , Ziad Koberssy 1 , Joviane Daher 1 , Kate Ailstock 4 , Morgan Cummings 4 , Nicholas Funderburg 4 , Grace A. McComsey 1 1 Case Western Reserve University, Cleveland, OH, USA, 2 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 3 Saint Joseph University, Beirut, Lebanon, 4 The Ohio State University, Columbus, OH, USA Background: Long COVID (LC) is characterized by recurrent, prolonged, and new symptoms of COVID-19 at least 3 months after a SARS-COV-2 infection.

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High-Fat and -Sugar Diet but Not SIV Coinfection Enhances SARS-CoV-2 Shedding in Infected Macaques Kelsie Brooks 1 , Arvind Sivanandham 2 , Quentin Le Hingrat 2 , Anna Jasinska 2 , Delmy Ruiz 1 , Lilly Carson 2 , Lilas Tarnus 2 , Mohammed Daira 2 , Makheni Jean Pierre 1 , Cristian Apetrei 2 , Jason Brenchley 1 , Ivona Pandrea 2 1 National Institutes of Health, Bethesda, MD, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: Numerous risk factors for severe SARS-CoV-2 infection have been identified, including diabetes, obesity, and cardiovascular disease. These conditions often co-occur and may be influenced by diet. We sought to

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CROI 2025