CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

groups for testosterone, DHEAS, TSH, ft3, or ft4. Median TSH was higher in the pathological FAS group (2.07 mU/L vs 1.58 mU/L; p=0.004). Conclusions: This study reveals a disrupted circadian cortisol rhythm in individuals post-COVID-19, marked by lower daytime and higher evening/ nighttime cortisol levels, potentially correlating with disease severity. Elevated ACTH levels in LC may suggest adrenal impairment. In Vitro Modeling of the Effects of Impaired HDL on Atherogenesis in Long COVID Syndrome Michael Wong 1 , Madhav Sharma 1 , Theodoros Kelesidis 2 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of Texas Southwestern Medical Center, Dallas, TX, USA Background: The mechanisms that drive SARS-CoV-2-related cardiovascular complications of Long COVID (PASC) such as atherosclerotic cardiovascular disease (CVD) remain unclear. Prior studies have shown alterations of HDL function in infections and SARS-CoV-2 infection, persistent oxidative stress, lipid abnormalities and macrophage dysfunction post COVID-19 that may contribute to HDL dysfunction and CVD. However, the effect of dysfunctional HDL on atherogenesis in PASC remains unknown. To address these gaps in knowledge, we used an established model of atherogenesis to assess ex vivo the role of impaired HDL on early atherogenesis in PASC. Methods: Our in vitro model of atherogenesis can dissect the impact of HDL from patients with PASC on key mechanisms of early atherogenesis such as transendothelial migration of monocytes (TEM) and monocyte-derived foam cell formation (MDFCF). ApoB depleted serum was isolated from healthy participants (n=15 males, 18-40 years old) and patients with PASC (n=15, 40-55 years old, 7 females, 8 males) with no risk factors for CVD or inflammatory comorbidities other than SARS-CoV-2 infection >12 weeks prior to study participation. Study participants were recruited within UCLA CTSI. PBMCs from healthy donors (n=15) or PASC patients were added to activated endothelial cells monolayers (HUVECs) on collagen gels and flow cytometry assessed % TEM of monocytes and MDFCF (BODIPY signal compared to staining control in the presence of ApoB depleted serum as previously (PMID: 28926407). Results: When media-containing PACS+ ApoB depleted serum was added to HUVECs and autologous PASC PBMC, a significantly increased proportion of monocytes underwent TEM(median migrated cells 19.04 vs. 7.5%, respectively) and CD33+ macrophages inside the collagen gel had increased lipid content per cell (median ∆MFI BODIPY 351.9 vs. 149.7, respectively)(P<0.001) compared to control ApoB depleted serum and healthy PBMCs, respectively (Figure). Conclusions: ApoB depleted serum from patients with PASC with no CVD and CVD risk factors directly induces key mechanisms of early atherogenesis (TEM and MDFCF) in a mechanistic ex vivo assay of atherogenesis in the presence of autologous PBMCs from the same PASC patients, suggesting that impaired HDL interacts with impaired monocytes to potentially contribute to atherogenesis in the setting of PASC. Further large studies in patients with PASC are needed to validate the role of dysfunctional HDL in Long COVID and recurrent SARS-CoV-2 infections. The figure, table, or graphic for this abstract has been removed.

and so we sought indirect evidence of persistent viral antigen by assessing for frequency of memory T cells specific for SARS-CoV-2 after SARS-CoV-2 infection in people with and without LC. Methods: We obtained 122 T cell receptor (TCR) β chain repertoires from sorted memory CD4+ and CD8+ T cells from longitudinal samples drawn at 1- and 4-6 months post-first SARS-CoV-2 infection from people who went on to develop LC (n=17) and those who experienced a full and rapid recovery (n=14, FR). ImmuneCODE-MIRA-Release002.1, a database of 160,000 public SARS-CoV-2 specific TCRβ sequences with linked antigen specificity, was used to determine the frequencies of public SARS-CoV-2-specific TCRs within memory CD4+ and CD8+ TCRβ repertoires. The frequencies of resting naïve and memory CD4+ & CD8+ T cells, activated CD4+ & CD8+ T cells, and monocyte subsets were also determined using flow cytometry. The sample was stratified into 'young' and 'old' groups based on age greater than or less than the median age (50) at time of infection. Results: The frequency of public SARS-CoV-2-responsive TCRs in memory CD4+ (p=0.54) and memory CD8+ (p=0.83) TCRβ repertoires did not differ between individuals with LC and FR at either 1- or 4-6-months post-infection, nor did they significantly change over time from 1 to 4-6 months post-infection. Immune cell frequencies did not differ, except that LC had lower frequencies of CD4s among all T cells at 4-6-months post-infection compared to FR (58.5% vs 66.6%, p=0.038). When stratified by age, older LC had significantly lower frequency of public SARS-CoV-2-responsive TCRs in memory CD4+ TCRβ repertoires than older FR (p=0.016), including public non-spike-(p=0.017) and spike-(p=0.04) specific TCRs compared to FR. Conversely, younger LC trended towards having a higher frequency of public SARS-CoV-2 TCRs among their memory CD4+ TCRβ repertoires than younger individuals with FR (p=0.088); this trend persisted when exclusively considering overlap with public non-spike, ORF7b, and ORF8-associated TCRs (p=0.055, 0.057, 0.063). Conclusions: Older individuals with LC had fewer public SARS-CoV-2-specific TCRs in their memory CD4+ T cell repertoires than their peers with full recovery. While these results warrant confirmation by other means, this work suggests that LC may not be associated with persistent antigen in older individuals.

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Poster Abstracts

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Persistent Immune Dysregulation and Metabolic Alterations Following SARS-CoV-2 Infection Silvia Lucena Lage 1 , Katherine Bricker-Holt 2 , Joseph Rocco 1 , Adam Rupert 3 , Eduardo Pinheiro Amaral 2 , Gabriel Rosenfeld 2 , Thomas Dalhuisen 4 , Avery Eun 4 , Emily Fehrman 4 , Jeffrey Martin 4 , Steven G. Deeks 4 , Michael Peluso 4 , Irini Sereti 1 , Timothy J. Henrich 4 1 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 2 National Institutes of Health, Bethesda, MD, USA, 3 Frederick National Laboratory for Cancer Research, Frederick, MD, USA, 4 University of California San Francisco, San Francisco, CA, USA Background: SARS-CoV-2 infection can lead to medical comorbidities (eg, autoimmunity, vascular complications) as well as Long COVID (LC), a multisystem disease encompassing a wide range of symptoms. The biological drivers of these conditions are incompletely understood. Methods: We performed an in-depth immunometabolic screen with multidimensional flow cytometry and plasma measurements of inflammatory biomarkers and metabolites. We compared SARS-CoV-2-naïve controls (NC, N=30) and individuals who had COVID-19 4 months prior to sampling (COVID, N=96). The post-COVID participants included those who had WHO-defined LC (LC, N=58) or had fully recovered (RC, N=38).

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Age-Dichotomous Associations of Long COVID With Frequency of Public SARS-CoV-2 Memory TCRs Selin Akbas 1 , Shuai Li 2 , Hao Zhang 2 , Tamilore Adeagbo 1 , Ni Zhao 2 , Alan Landay 3 , Michael Peluso 4 , Elizabeth Thompson 1 , Andrea Cox 1 , Yukari Manabe 1 , Hongkai Ji 2 , Annukka Antar 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Texas Medical Branch, Galveston, TX, USA, 4 University of California San Francisco, San Francisco, CA, USA Background: Despite its prevalence, the pathobiological mechanisms of long COVID (LC) remain unknown. Persistent SARS-CoV-2 viral antigen may cause LC,

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