CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

947

Post-Acute SARS-CoV-2 Antigenemia Is Associated With Some But Not All Long COVID Symptoms Michael Peluso 1 , Thomas Dalhuisen 1 , Zoe Swank 2 , Sarah Goldberg 1 , Scott Lu 1 , Samuel Han 2 , Jessica Chen 1 , Emily Fehrman 1 , Khamal Anglin 1 , Rebecca Hoh 1 , Timothy J. Henrich 1 , Dan Kelly 1 , Steven G. Deeks 1 , David Walt 2 , Jeffrey Martin 1 , for the UCSF LIINC Team 1 University of California San Francisco, San Francisco, CA, USA, 2 Brigham and Women's Hospital, Boston, MA, USA Background: SARS-CoV-2 (SCV2) RNA and antigens can be found in several tissues many months after infection, but whether SCV2 persistence causes Long COVID (LC) is unproven. The scant data in favor of causation has related persistent SCV2 to non-specific LC definitions. It is unknown whether persistent SCV2 is associated with all, or only some, of the different symptoms of this heterogenous condition. Methods: Sampling from UCSF’s LIINC cohort, we defined 5 LC case groups and 1 non-LC control group. Consistent with the NASEM definition, LC groups had ≥1 symptom in a given grouping that was rated “very bothersome” at ≥2 visits 3-14 months after the first confirmed SCV2 infection. LC case groups were: a) neurologic (headache, brain fog or dizziness); b) cardiopulmonary (cough, dyspnea, chest pain or palpitations); c) gastrointestinal (GI; nausea, vomiting, diarrhea, constipation, belly pain or appetite loss); d) musculoskeletal (back, joint or muscle pain); and e) fatigue. The non-LC group was those whose acute symptoms resolved within 30 days of infection and who had no symptoms 3-14 months post-infection. SCV2 spike, S1, and nucleocapsid (N) antigens were measured in plasma by single molecule array (Simoa) assay. Odds ratios (OR) were used to relate antigenemia at any visit 3-14 months post-infection to concurrent symptoms. Results: Spike antigenemia was found in 7.5% (3/40) of the non-LC group. In unadjusted analyses, spike antigenemia was associated with neurologic, cardiopulmonary, and musculoskeletal symptoms but not GI or fatigue (Table). After adjustment for confounding, associations endured for neurologic (OR 4.5, p=0.037), cardiopulmonary (OR 4.8, p=0.08), and musculoskeletal (OR 5.5, p=0.049) symptoms. After exclusion of timepoints within 1 month of known SCV2 vaccination or reinfection, point estimates were similar but confidence intervals widened slightly. No significant associations were seen with S1 or N antigens. Conclusions: Among adults with prior SCV2 infection, we found evidence for an association between SCV2 spike antigenemia 3-14 months post-infection and some but not all LC symptoms. This work highlights the need for well characterized participants, with and without a variety of symptoms, to yield associations, and it suggests that different mechanisms might contribute to the variable presentation of LC. Nonetheless, given the novelty of the system, more work is needed (including intervention studies) to confirm the findings and exclude confounding before causation is inferred.

with both PASC along with the development of AA, and thus may be driving ACE2 AA development and subsequent inflammation. Future studies are planned to assess the correlation of ACE2 AA with circulating levels of soluble ACE2 and RAS peptides.

Poster Abstracts

946

Shared Autoantibody Signature Is Not Identified in CSF During Long COVID Debanjana Chakravarty 1 , Thomas Ngo 1 , Lindsay S. McAlpine 2 , Jennifer Chiarella 2 , Allison Nelson 2 , Iris Tilton 1 , Ravi Dandekar 1 , Vishal Lashkari 1 , PeiXi Chen 1 , Kelsey Zorn 1 , Shelli Farhadian 2 , Serena Spudich 2 , Samuel Pleasure 1 , Michael Wilson 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Yale University, New Haven, CT, USA Background: A subset of people who recover from acute COVID-19 develop a range of emergent or persistent symptoms lasting months to years, collectively termed Long COVID (LC). We investigated whether autoimmune antibodies in the CNS associate with neurologic Long COVID symptoms (n-LC). Methods: Participants with LC (WHO criteria) and cognitive symptoms or headache enrolled in The COVID Mind Study (n-LC, n=38). Controls (n=16) were healthy pre-pandemic participants (n=13) or post-COVID without any LC symptoms (n=3). Cerebrospinal fluid (CSF) was collected for research. Mouse brain sections were immunostained with CSF from n-LC and controls at 1:4 dilution and visualized with anti-human IgG to screen for anti-neural autoantibodies. CSF IgG was incubated with a human proteome-wide phage display library (PhIP-Seq) to identify candidate antibody targets enriched in n-LC compared to controls (enrichment threshold of sum rpk>100, fold change>10, z-score>3). We orthogonally validated candidate autoantigen by split-luciferase-binding assay (SLBA) and HEK293T cell overexpression. Results: 14/38 n-LC samples showed positive staining on mouse brain sections, with moderate to strong cytoplasmic and nuclear staining, specifically in the thalamus, cortex, hippocampus, and brainstem. 6/13 never-COVID and 3/3 post COVID controls displayed similar cytonuclear staining patterns in mostly all brain regions. Using PhIP-Seq, we identified human peptides bound to antibodies present in n-LC CSF. Only the top 40 peptides that enriched in positively stained n-LC samples above negatively stained n-LC and control CSF are plotted in the heatmap (Figure1a). We chose Sox5 for further validation because, only Sox5 peptides showed enrichment in the highest number of participants (n=3), while most other peptides enriched in only one participant. Moreover, unlike other top peptides, Sox5 has CNS-specific functions involving neuronal signaling. Also, logistic regression showed SOX5 as the most discriminatory gene between positive and negatively stained n-LC samples. However, enriched SOX5 autoantigens did not validate with SLBA and cell-based overexpression assay. Conclusions: Whole human proteome antigen discovery with CSF from individuals with and without n-LC did not identify a shared autoantigen in n-LC. There was no difference in the frequency and pattern of immunostaining on rodent brain slices between n-LC and controls. Our preliminary work did not identify a unified autoantibody signature in the CSF of patients with n-LC.

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CROI 2025 297