CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Several markers previously associated with neurodegenerative and psychiatric diseases were significantly altered during acute COVID-19. Notably, neuronal pentraxin-2 (a sensitive marker of cognitive decline in AD) remained unaffected. Importantly, no biomarker evidence of persisting CNS pathology was seen at follow-up either between patients and controls, or between patients with or without PCC indicating that PCC is not associated with progressive postinfectious neurodegeneration. The figure, table, or graphic for this abstract has been removed. SARS-CoV-2 Nucleocapsid Antigen is Not Detected in the CSF During Long COVID Shelli Farhadian 1 , Allison Grubman 1 , Lindsay S. McAlpine 1 , Bibhuprasad Das 1 , Jennifer Chiarella 1 , Benjamin Orlinick 1 , Hailey Reisert 1 , Allison Nelson 1 , Priya Kosana 1 , Meenakshi Khare 2 , Serena Spudich 1 1 Yale University, New Haven, CT, USA, 2 Quanterix Corporation, Lexington, MA, USA Background: SARS-CoV-2 viral protein persistence has been suggested as a possible cause of post acute sequelae of COVID-19. We previously showed that some individuals with neuropsychiatric symptoms after COVID-19 had persistent anti-SARS-CoV-2 nucleocapsid antibodies in the cerebrospinal fluid (CSF) several months after COVID-19. However, it is unknown whether this is driven by persistence of SARS-CoV-2 antigen in the CSF. Methods: CSF and plasma was collected from participants in four groups: acute COVID (hospitalized with acute-infection, n=5); post-COVID with neuropsychiatric symptoms (Neuro-PASC, n=31); post-COVID asymptomatic (n=8), and pre-pandemic never-COVID controls (n=20). Tissue samples were measured for SARS-CoV-2 Nucleocapsid (N) antigen levels via a Single Molecular Array (Simoa) immunoassay, a paramagnetic microbead-based sandwich ELISA (Quanterix, Billerica, MA, USA). Samples were run in duplicate, and the results were averaged. CSF was run undiluted and plasma samples were diluted 1:4 per manufacturer protocol, with results corrected for dilutions. Results: Sixty-four participants' samples were analyzed: sixty-one paired CSF and plasma samples and three CSF samples. Acute COVID participants were sampled a median of 7 days (range 1-14) after symptom onset. Neuro-PASC and post-COVID asymptomatic participants were sampled a median of 381 days (range 81-1157) after acute infection. SARS-CoV-2 N-antigen was not detected in any of the post-COVID (Neuro-PASC or asymptomatic) or pre-pandemic participants, in CSF or plasma. SARS-CoV-2 N-antigen was detected in the CSF or plasma of three participants, all of whom were from the acute COVID cohort. Of these three participants, one had antigen present in the CSF sample (1.40 pg/ mL), one had antigen present in the plasma sample (29.9 pg/mL), and one had antigen present in both the CSF and plasma samples (12.6 pg/mL and 785 pg/ mL, respectively). Conclusion: We found SARS-CoV-2 N-antigen is undetectable in the plasma and CSF of post-COVID participants, those with Neuro-PASC and those without PASC. Neuro-PASC is unlikely to be caused by persistent SARS-CoV-2 N-antigen in the CNS.

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Gut Microbiome Dysbiosis and Lower Abundance of Butyrate Producing Bacteria in Neurologic PASC Lawrence Purpura , Lingsheng Wen, Heekuk Park, Ga Young Seo, Jayesh Shah, Amanda Castillo, Anne-Catrin Uhlemann, Michael T. Yin Columbia University Medical Center, New York, NY, USA Background: Neurologic post-acute sequelae of COVID-19 (PASC) affects a growing population of individuals, with symptoms including myalgic encephalomyelitis chronic fatigue syndrome (ME-CFS), cognitive dysfunction, dysautonomia, and neuropathy. Gut microbiome dysbiosis has been reported in the early convalescent period after SARS-COV-2 infection (<1 year) in hospitalized patients, with lower alpha diversity and decreased abundance of butyrate-producing species. Butyrate has a protective effect in the gut by supporting the mucosal barrier and has systemic anti-inflammatory and immunomodulatory effects. Notably, in long-term ME-CFS patients (symptoms >10 years), metabolic dysfunction persists despite recovery of relative abundance of bacterial species. To date, the longitudinal role of gut dysbiosis in neurologic PASC remains unknown, especially in patients with mild acute COVID-19. Methods: The COVID-19 Persistent and Immunology Cohort (C-PIC) is an observational cohort study with over 650 participants, with and without PASC. Rectal swabs or stool samples are collected at 3-6 month intervals, with matched clinical metadata. Neurologic PASC is defined as self-reported fatigue, cognitive dysfunction, or dysautonomia. DNA was extracted using the Zymo MagBead DNA/RNA kit and the MiSeq platform was used to sequence the V3/ V4 region of the bacterial16s rRNA gene. DESeq2 was used to assess species level differential abundance testing and alpha diversity was measured using Chao scores for richness. Differences between participants with and without neurologic PASC were compared in C-PIC participants with mild acute COVID-19 not requiring hospitalization. Results: 151 C-PIC participants with mild acute COVID-19 were included in the analysis. Fecal samples collected at study enrollment demonstrated lower relative abundance of butyrate-producing species (Faecalibacterium prausnitzii, Eubacterium spp, Bacteroides spp) in participants reporting neurologic PASC (p<0.05). We also report a trend toward increasing alpha diversity (chao) over time across 371 longitudinal samples (figure). Conclusion: Our findings of decreased abundance of butyrate-producing bacterial species in patients reporting neurologic PASC and a trend towards improving alpha diversity after recovery from SARS-CoV-2 align with late convalescent findings in ME-CFS. These data provide support for the role of gut microbiome in neurologic PASC. Further research is needed to identify gut microbiome targets for diagnostics and therapeutics.

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Poster Abstracts

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Brain White Matter Hyperintensity Accumulation in an Acute HIV Cohort Over 2 Years Kathryn Holroyd 1 , Jacob Bolzenius 2 , Carlo P. Sacdalan 3 , Netsiri Dumrongpisutikul 4 , Somchai Sriplienchan 3 , Pathariya Promsena 3 , Sandhya Vasan 5 , Lydie Trautmann 5 , Serena Spudich 1 , Phillip Chan 1 , Robert Paul 2 , RV254/ SEARCH 010 Study Team 3 1 Yale University, New Haven, CT, USA, 2 University of Missouri St Louis, St Louis, MO, USA, 3 SEARCH, Bangkok, Thailand, 4 Chulalongkorn University, Bangkok, Thailand, 5 US Military HIV Research Program, Silver Spring, MD, USA Background: Development and progression of cerebral white matter hyperintensities (WMH) are associated with increased risk of stroke and cognitive impairment for people with (PWH) and without HIV (PWOH). Individuals with chronic HIV have greater WMH burden compared to PWOH

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