CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: We evaluated 200 individuals in the UCSF LIINC post-COVID study cross-sectionally, 3-6 months after SARS-CoV-2 infection. We defined LC as ≥1 COVID-attributed symptom (n=144), and non-LC (nLC) as no symptoms (n=56). We further defined those with LC who met Institute of Medicine ME/ CFS criteria at 3 months as LC-ME (n=28) and those with LC but without LC-ME as LC-nME (n= 116). We measured cortisol on serum collected 8AM-12PM on day of assessment and performed analyses stratified by collection time. Results: The cohort was 55% female; median age was 43. Cortisol levels (µg/dL) did not differ between LC and nLC groups (median 8.9 vs 8.8) when aggregated across collection time. Proportions with subnormal cortisol levels (<5) were similar (9.7% vs 8.9%). When stratified by collection time, 8-9AM cortisol levels tended to be lower in those with LC compared to nLC (12.4 vs 14.9, p=0.36), and 9-10AM cortisol levels tended to be higher comparing LC to nLC (10.3 vs 8.5, p=0.15), albeit neither difference was statistically significant. No differences were observed between 10-11AM and 11AM-12PM. When stratified by post-COVID ME status, cortisol levels between 8-9AM were significantly lower in the LC-ME group compared to the nLC group (8.2 vs 14.8, p=0.02), even after adjusting for age, sex and BMI (Fig 1). Conversely, cortisol levels between 9-10AM were significantly higher in the LC-ME group compared to the nLC group (13.7 vs 8.5, p=0.02), also after adjusting for age, sex, and BMI (Fig 1). No differences were observed comparing LC-nME to nLC. Conclusion: We found that cortisol levels tended to be lower between 8-9AM and to be higher between 9-10AM in those with LC, and that this difference appears to be driven by those with LC-ME, consistent with prior observations of a delayed cortisol peak in ME/CFS. These findings significantly add to our understanding of cortisol in LC and highlight the importance of considering collection time. Longitudinal measures of cortisol in individuals with LC will be critical to further inform the biology of the condition.

to systemic inflammation, antiviral cytokine responses, endothelial dysfunction, tissue damage, coagulation, microbial translocation, innate immune activation, immune regulation and axonal injury using quantitative immunoassays. We used principal component analysis and unsupervised hierarchical clustering to identify distinctive biological clusters. We used Kruskal-Wallis and Chi-Square tests to explore demographic and clinical parameter differences between clusters. Results: We included 364 individuals (median (IQR) age 44 (35-53) years, BMI 27 (22-32), 74% female, 85% Caucasian) in the analysis. We identified 6 distinct biological clusters (Figure 1 A). Clusters 1,2 and 3 (68,9%) exhibited low inflammatory biomarkers, lower BMI, younger age, and fewer comorbidities. In contrast, clusters 4,5 and 6 were characterized by higher inflammatory profiles. Cluster 4 characterized by higher innate immune activation markers, had the highest BMI, oldest age, and more prevalent comorbidities like hypertension and obesity, suggesting metabolic syndrome. In contrast, cluster 5 had higher anti-inflammatory (IL2, IL4, IL10) and antiviral biomarkers (IFN-α2a, IFN-B) and was relatively younger, suggesting a persistent immune response to infection. Cluster 6, mainly cardiorespiratory (60%) (Fig-1 B), and higher expression levels of tissue damage biomarkers (VEGF, EGF, PDGF, TGF-α, β-NGF), coagulation (CD40L, P-selectin, TPO, vWF), and axonal injury (S100A9, S100B, Tau, ENO2, UCH-L1) and had higher reported respiratory illness. Conclusion: From 6 distinct biological clusters, we identified three inflammatory clusters in individuals with long COVID with specific clinical and biological characteristics, including patterns suggesting tissue damage/ coagulation and persistent antiviral immune responses. The data suggest a number of distinct underlying pathogenesis in individuals with long COVID.

Poster Abstracts

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Association of Long COVID With Health-Related Quality-of-Life Outcomes Malini M Gandhi 1 , Carlee Moser 2 , Judith S. Currier 3 , Justin Ritz 2 , Joseph J. Eron 4 , Eric Daar 5 , David Wohl 4 , William Fischer 4 , Upinder Singh 6 , Michael D. Hughes 2 , Davey M. Smith 7 , Teresa H. Evering 8 , Kara W. Chew 3 , for the ACTIV-2/ A5401 Study Team 1 Harvard Medical School, Boston, MA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Harbor–UCLA Medical Center, Torrance, CA, USA, 6 Stanford University, Stanford, CA, USA, 7 University of California San Diego, La Jolla, CA, USA, 8 Weill Cornell Medicine, New York, NY, USA Background: Long COVID is a significant and growing public health burden. The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Methods: Participants (N=546) who received blinded placebo in the ACTIV-2/ A5401 outpatient COVID-19 treatment trial with symptom diary data at week 24 were assessed for long COVID, defined as presence of self-assessed COVID-19 symptoms within the last 4 weeks at the week 24 visit. HrQOL at week 24 was evaluated by the EQ-5D-5L (EQ-5D) and SF-36v2 (SF-36) questionnaires. Modified Poisson regression and Wilcoxon rank-sum tests compared EQ-5D and SF-36 measures between participants with vs without long COVID. Results: This cohort enrolled between January and August, 2021; median age was 44 years, median time from symptom onset was 5 days; 53% female, 99% cisgender, 80% White, 13% Black, 53% Hispanic, 58% high-risk for severe COVID-19, 36% with Delta and 64% pre-Delta variant infection, 16% vaccinated, and 52% anti-nucleocapsid or anti-spike antibody positive. Long COVID was present in 13.6% (74/546) of participants. EQ-5D was completed by 80% and

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Relationship Between Serum Cortisol Level and Long COVID Symptoms in Post-Acute COVID-19 Thomas Dalhuisen , Joshua Hauser, Scott Lu, Lucas Kallás Silva, Rebecca Hoh, Steven G. Deeks, J. D. Kelly, Jeffrey Martin, Peter W. Hunt, Elizabeth Murphy, Timothy J. Henrich, Morrie Schambelan, Michael J. Peluso, for the LIINC Study Team University of California San Francisco, San Francisco, CA, USA Background: Low cortisol levels have been reported in some people with Long COVID (LC), but this observation has yet to be confirmed. Some people with LC meet the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness that has also been associated with cortisol dysregulation. Further evaluation of cortisol post-COVID could better define LC biology.

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