CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: Our findings showed a distinct humoral immunological profile in LCD. Increased levels of antiphospholipid autoantibodies may interact with the central and peripheral nervous systems, leading to neuropathies and possibly dysautonomia. Additionally, our LCD cohort had reduced plasma levels of total IgG despite higher total B-cell levels, coupled with decreased BLyS and APRIL expression, indicating a potential B-cell dysfunction and lower protection against SARS-CoV-2 reinfections. These results provide novel insights into the immunopathological mechanisms of LC-related dysautonomia and potential therapeutic targets. Long COVID Associates With Slow Viral Clearance and Viral Rebound During Acute SARS-CoV-2 Infection Carly Herbert 1 , Nisha Ramdeep 2 , Annukka Antar 2 , John Broach 1 , Colton Wright 1 , Pamela Stamegna 1 , Katherine Luzuriaga 1 , Nathaniel Hafer 1 , David McManus 1 , Yukari Manabe 2 , Apurv Soni 1 1 University of Massachusetts, Worcester, MA, USA, 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: SARS-CoV-2-host dynamics during acute infection appear to be important in the development of long COVID. However, prior studies were limited by cohort size and infrequent sampling during acute infection, and no study has addressed the association of viral rebound and long COVID. Here we present data from a large cohort study that tested people without COVID-19 on a daily or every-other-day basis to catch the onset and clearance of SARS CoV-2 RNA from the upper respiratory tract with unprecedented resolution, facilitating a more definitive investigation of early virus-host dynamics and their association with long COVID. Methods: Between Oct. 2021 and Feb. 2022, 7,361 people self-collected nasal specimens for SARS-CoV-2 RT-PCR testing every 24 or 48 hours for 10 or 14 days in the Test Us At Home studies. In August 2023 (18-22 months after enrollment), 244 participants with first SARS-CoV-2 infection and >1 positive test were asked whether they had ever had long COVID, defined as new COVID-associated symptoms present for 3+ months post-infection. The relative risk of developing long COVID was calculated using a log binomial model with modeled viral clearance slopes as the exposure adjusted for age, number of symptoms, and SARS-CoV-2 variant. Viral rebound was defined as testing positive, then negative, then positive again. In the viral rebound analysis, only participants with ≥3 tests were included (n=215). Logistic models were used to examine associations among symptoms, demographics, viral rebound, and long COVID. Results: Slopes of viral clearance were able to be modeled for 172 participants, of whom 59 (34%) ever had long COVID. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance than those who never developed long COVID (10.0 days [95% CI: 9.25-10.8] vs 8.7 [95% CI: 8.28-9.01]). Slopes were significantly associated with four post-acute symptoms: fatigue (aRR: 2.9), brain fog (aRR: 4.94), shortness of breath (aRR: 5.05), and gastrointestinal symptoms (aRR: 54.6) (Figure). Of the 215 participants assessed for viral rebound, 77 (36%) ever had long COVID and 75 (35%) experienced viral rebound. The development of long COVID was associated with 13-fold higher odds of having experienced rebound during acute infection (OR: 13.1; 95% CI: 6.79-26.2). Conclusions: We demonstrate here that slow viral clearance and viral rebound during acute infection are associated with long COVID. Preserved Adrenal Function in People With Long COVID Annukka Antar 1 , Armaan Jamal 1 , Zoe O. Demko 1 , Elizabeth Pasetes 1 , Tamilore Adeagbo 1 , Selin Akbas 1 , Cherie Marvel 1 , Andrea Cox 1 , Michael Peluso 2 , Alan Landay 3 , Neal Fedarko 1 , Amir Hamrahian 1 , Tracy Vannorsdall 1 , Alba M. Azola 1 , Yukari Manabe 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 University of Texas Medical Branch, Galveston, TX, USA Background: Low serum cortisol has been associated with long COVID (LC) in some but not all studies. However, these studies examined untimed cortisol levels, which may not adequately assess adrenal function. Here we assessed untimed, timed, and stimulated cortisol levels and tested their association with LC. Methods: Untimed total cortisol levels were quantified in 711 serum samples obtained 1-12 months post-SARS-CoV-2 infection in 381 participants enrolled in two cohort studies between 2020-2022. LC at the time of blood draw was The figure, table, or graphic for this abstract has been removed.

compared to participants imaged prior to the COVID-19 pandemic using a novel PET imaging tracer of T cell activation ([ 18 F]F-AraG). The relationships between persistent whole-body T cell activation and various Long COVID (LC) clinical phenotypes, however, is not known. Thus, we performed PET imaging on 65 individuals months to years following initial COVID-19 infection and analyzed [ 18 F]F-AraG distribution across the whole body. Methods: Whole-body PET/CT imaging was performed ~50 minutes following [ 18 F]F-AraG IV injection (5mCi) . Standardized uptake values (SUV) across tissue regions of interest in people with LC (n=50) at the time of imaging was compared to those who recovered rapidly after initial infection (n=15). Comparisons between LC phenotypes and SUV were performed adjusting for false discovery within tissue groups. Results: We observed significant higher rectosigmoid wall mean SUVs in people with LC versus fully recovered (0.78 vs 0.51, P=0.019) and in people reporting cardiopulmonary (CP) symptoms (n=37; i.e., cough, shortness of breath, heart rhythm abnormalities, chest pain) vs the 28 participants that did not report CP symptoms (0.84 vs 0.57, respectively; P=0.013). Whereas we identified a non-significant trend to higher gut tracer uptake in people reporting fatigue vs those not reporting fatigue (SUVmean 0.78 vs 0.61) there were no trends or visualized differences across tissues in other LC phenotypes (including fatigue, sleep disturbances, musculoskeletal, gastrointestinal, neurocognitive). [ 18 F]F-AraG uptake was similar for all other tissue regions of interest in those with LC and various LC clinical phenotypes. Conclusions: Non-invasive PET imaging revealed increased uptake of T cell activation in colorectal tissue in those with Long COVID versus those who were fully recovered, and was specific for those reporting cardiopulmonary, but not other LC symptoms. These findings, however, may be confounded by subclinical re-infections, vaccinations or other factors. Nonetheless, these data support a hypothesis of ongoing GI mucosal dysfunction and potential viral persistence driving LC. Our data also suggest that the etiology of various LC clinical phenotypes is likely heterogeneous and may need to be considered as different etiologic entities. Evidence of B-Cell Dysfunction in Individuals With Long COVID Associated Dysautonomia Montserrat Torres 1 , Clara Sánchez Menéndez 1 , Alicia Simón Rueda 1 , Ana García Casas 2 , Jaime Bartolomé 1 , Luis Fernando Lemus Aguilar 1 , Elena Mateos 1 , Jose Aguareles 2 , Guillermo Santamaria Corral 2 , Aránzazu Murciano Anton 3 , Pablo Guisado Vasco MD, MPH, PhD 2 , Mayte Coiras 1 1 Instituto de Salud Carlos III, Madrid, Spain, 2 Hospital Universitario Quironsalud Madrid, Madrid, Spain, 3 Primary Healthcare Center Doctor Pedro Laín Entralgo, Madrid, Spain Background: Long COVID (LC) can trigger dysautonomia or dysfunction of the autonomic nervous system (ANS) similar to some autoimmune diseases. Dysautonomia has been related with autoantibodies produced by activated non-specific B-cell clones that may interfere with the ANS normal function. Our objective was to analyze alterations in the humoral immunity with a specific focus on the BLyS/APRIL signalling pathway, which is essential for B-cell activation and regulation, to elucidate potential molecular mechanisms underlying dysautonomia in LC. Methods: Comparative, observational, cross-sectional study comprising people with LC exhibiting dysautonomia (LCD; n=26) and healthy donors (HD; n=42). Peripheral blood mononuclear cells (PBMCs) were immunophenotyped by flow cytometry. Plasma cytokines were measured by multiplex immunoassay. Total IgG and autoantibodies were quantified by ELISA. Results: LCD had a median age of 46 years (IQR 42-52) while HD had 45 years (IQR 39-52); most participants were female (89 and 86%, respectively). 2) Total B cell levels (CD3-CD19+) were increased 1.6-fold in LCD compared to HD (p=0.0396). However, the levels of total B cells and activated memory B cells (CD10-CD27+CD21low) expressing APRIL (A-PRoliferation-Inducing Ligand) on the cell surface were significantly lower in LCD (p=0.0014 and p=0.0021, respectively). 3) Similarly, LCD showed reduced plasma levels of both APRIL (-1.2-fold; p=0.0342) and BLyS (B-Lymphocyte Stimulator) (-1.3-fold; p=0.0287). 4) According to this reduced B-cell activation, total IgG levels and specific against SARS-CoV-2 were 1.6-fold (p=0.0172; and p=0.0153, respectively) lower in LCD. 5) The analysis of several autoantibodies in plasma revealed positive results only for antiphospholipid IgG and IgM in some participants with LCD. 6) LCD had 2.4 times more breakthrough infections than HD (p=0.0291).

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Poster Abstracts

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CROI 2025 293

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