CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

investigate the impact of diet directly on SARS-CoV-2 infection, as well as the understudied area of SARS-CoV-2 and HIV co-infection, which we modeled with SIV infection in macaques. Methods: Three control pigtail macaques (PTM, 1F & 2M) were infected with 1x10 6 TCID 50 Delta strain SARS-CoV-2 and monitored following infection until euthanasia and necropsy (Nx) on day 30. Six additional PTM (3M, 3F) were fed a high fat and sugar chow (HFD) for 63 days prior to SARS-CoV-2 infection, then followed until euthanasia and Nx on days 30-32 SARS-CoV-2. A final six PTM (4M, 2F) were fed the HFD prior to SIV infection (IV SIV agm ), then infected with SARS-CoV-2 on day 35 of SIV and monitored until euthanasia and Nx on days 30-32 of SARS-CoV-2. Results: Macaques fed the HFD experienced significant shifts in stool bacteria Beta diversity from pre- to post-HFD time points before infection (Adonis testing, unweighted UniFrac distances). All three groups demonstrated significant shifts in Beta diversity from prior to SARS-CoV-2 infection and SARS CoV-2 time points, though this did not remain significant for control animals with weighted UniFrac distances. HFD fed, SIV+ animals expressed significantly more MX1 transcript in Nx colon tissue and bronchioalveolar lavage (BAL) cells at day 28 of SARS-CoV-2 than HFD fed, SIV- animals, suggesting an enhanced inflammatory response with SIV infection. Three other immune-related transcripts were also significantly elevated in BAL cells of HFD, SIV+ animals vs. HFD, SIV-, while 72 immune-related transcripts were significantly elevated in BAL cells from HFD, SIV- animals vs. controls. SARS-CoV-2 RNA, including subgenomic RNA indicating viral replication, was shed at considerably higher levels and for longer durations in HFD fed, SIV- animals than controls in both the stool and nose swabs, while shedding was not markedly different in HFD fed SIV+ vs. SIV- animals. Conclusions: Dietary change alone resulted in distinct alterations to the gut microbiome and SARS-CoV-2 shedding from the gastrointestinal as well as respiratory tracts, while SARS-CoV-2 shedding was not significantly altered by SIV co-infection. However, immune responses to SARS-CoV-2 appear distinct in SIV+ and SIV- animals, with a potentially heightened inflammatory state in SIV+ macaques. Sustained Inflammation and Delayed Resolution of COVID-19 Disease in SIV-Infected Macaques Dhiraj K. Singh, Gayathri Ravichandran, Garima Arora, Xavier Alvarez, Ricardo Carrion, Shannan Hall-Ursone, Edward Dick, Deepak Kaushal Texas Biomedical Research Institute, San Antonio, TX, USA Background: COVID-19 continues to be a health challenge with critical knowledge gaps existing in the understanding of mechanisms driving severity in comorbid conditions. Clinical observations points to a higher susceptibility to COVID-19 in people living with HIV (PLHIV) but the precise mechanisms are still unknown. Methods: Our group was amongst few that established the rhesus macaque model of COVID-19 infection early on during the pandemic. We are now leveraging this established NHP model of COVID-19 with the long-standing, highly validated, pathogenic AIDS NHP model to study a central hypothesis that underlying SIV infection and the resulting immune activation promotes severity of COVID-19 presentation by profiling the dynamics of viral titers (measured via molecular virology), induced tissue pathology (measured via live PET/CT imaging and conventional histopathology), and underlying immunological perturbations (measured via flow cytometry and single cell transcriptomics). Results: Macaques infected with SIV develop acute immunodeficiency within 2-4 weeks and progress to chronic AIDS over 5-6 months. When infected with SARS-CoV-2 these macaques develop mild-to-moderate COVID-19 with an extended acute hyperinflammatory state. Co-infected macaques demonstrate higher etiology of either diseases, enhanced lung and brain involvement as measured by PET/CT. Post SARS-CoV-2 infection in SIV coinfected macaque, the F-18 FDG uptake increased in lymph nodes, brain and gut during the acute phase followed by a decline in the post-acute phase. Investigations of the underlying specific immune mechanisms revealed perturbations in the airway myeloid cell composition, T cell phenotypes, activation status and antigenic responsiveness. Conclusions: Our study elucidates the dynamic immunological landscape and mechanistic interplays in the host coinfected with SIV and SARS-CoV-2. COVID-19 in SIV co-infected macaques is characterized by extended acute hyperinflammatory phase and delayed resolution of disease. Mechanistic insights developed by this study may inform future development of

immunotherapeutic interventions for combating COVID-19 as well as PASC in PLHIV. Monocyte Dysregulation in PASC With Ongoing Pulmonary Symptoms Thomas K. Awamura, Stefanos Giannakopoulos, Dominic C. Chow, Cecilia M. Shikuma, Gehan Devendra, Vedbar Khadka, Juwon Park University of Hawaii at Manoa, Honolulu, HI, USA Background: As the number of COVID-19 survivors amongst the global population continues to rise, the rates of chronic sequelae after recovery known as post-acute sequelae of COVID19 (PASC), have increased, emerging as a significant public health concern. Studies have shown that excessive monocyte activation is involved in the development of a cytokine storm and subsequent acute lung injury induced by acute SARS-CoV-2 infection. However, long-term consequence of COVID-19 on monocyte dysregulation and its contribution to PASC development has not been fully understood. We characterized transcriptomic changes in circulating monocytes associated with PASC with persistent pulmonary symptoms (PPASC) and how it affects inflammation and persistence of pulmonary symptoms. Methods: A total of 31 monocyte RNA samples were collected from blood of the study participants enrolled in three groups: individuals with PASC with pulmonary symptoms (PPASC, n=14), individuals who recovered from COVID-19 infection but no residual symptoms (Recovered, n=8), and healthy individuals with no COVID-19 infection confirmed by antibody test (Healthy, n=9). Transcriptomic profiling of monocytes was performed by bulk RNA sequencing to determine the relationship between monocytes states among the groups. Ingenuity pathway analysis (IPA) was used to identify relevant dysregulated cellular pathways and associated disease pathways. Results: In comparison to Recovered and Healthy, PPASC had an enrichment of immune activation signatures, such as neutrophil degranulation, production of nitric oxide and reactive oxygen species in macrophages, and IL-8 and IL-6 signaling, while IL-10 pathway was down-regulated (Figure 1). Monocytes from PPASC displayed up-regulation of pathways associated with immune responses of macrophages and chronic inflammation. Disease pathway analysis showed genes associated with inflammation and pulmonary diseases, such as chronic inflammatory disorder, vasculitis, and interstitial pneumonia, were activated in PPASC compared to Recovered. Conclusions: Transcriptomic analysis revealed that monocytes from PPASC individuals were continuously dysregulated with up regulation of pathways associated with immune activation, inflammation, and fibrosis. However, the gene signatures of monocytes from Recovered were comparatively similar to those of Healthy. Our data demonstrates that monocyte dysregulation persists after viral resolution, impacting the pulmonary sequelae in PASC individuals.

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CROI 2025