CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

341

Prolonged SARS-CoV-2 Viral Burden and Impaired Immunity in SIV/ SARS-CoV-2 Coinfected Macaques Megan N Fredericks 1 , Hannah Frizzell 1 , Hillary Tunggal 1 , Cecily C. Midkiff 2 , Jeana Barrow 3 , Anthony L. Cook 4 , Robert V. Blair 2 , Ankur Sharma 4 , Deborah H. Fuller 1 , Megan O'Connor 1 1 University of Washington, Seattle, WA, USA, 2 Tulane National Primate Research Center, Covington, LA, USA, 3 Washington National Primate Research Center, Seattle, WA, USA, 4 Bioqual, Inc, Rockville, MD, USA Background: People living with HIV (PLWH) have increased risk of morbidity and mortality from COVID-19. SARS-CoV-2 infection in PLWH poses a risk of prolonged infection and viral shedding, and emergence of variants of concern. Using the SIV macaque model for AIDS, we test the hypothesis that immune dysfunction during HIV infection alters SARS-CoV-2 viral infection and COVID-19 disease. Methods: Eight female rhesus macaques were intravaginally infected with SIVmac251, then intranasally and intratracheally inoculated with SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV inoculation. Blood, bronchoalveolar lavage, stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI). ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Results: We observed no significant changes in SIV clinical symptoms or viremia post-SARS-CoV-2 co- infection, and COVID-19 disease was typically mild. At 14 DPI, SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract. Notably, SARS-CoV-2 RNA levels in nasal swabs were significantly higher 7- 10 DPI in SIV+/SARS-CoV-2 infected rhesus when compared to published data in SIV-/SARS-CoV-2 rhesus (PMCID: PMC8462335, PMC8829873). Anti-SARS-CoV-2 binding antibodies in sera were significantly lower in the SIV+ macaques when compared to those from historical SIV-/SARS CoV-2 infected controls. Furthermore, generation of SARS-CoV-2 spike-specific T-cell responses were hindered at 14 DPI. Conclusion: Here, we provide evidence for the utility of the rhesus macaque in modeling human HIV/SARS- CoV-2 co-infection. Our results suggest that SIV induced immunosuppression impairs generation of anti-SARS- CoV-2 immunity, that may, in turn, contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine whether SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques. Viral Shedding and Mucosal Lymphocyte Disruptions in SARS-CoV-2 Infection Exacerbated by Fatty Diet Kelsie Brooks 1 , Arvind Sivanandham 2 , Quentin Le Hingrat 2 , Anna Jasinska 2 , Delmy Ruiz 1 , Lilly Carson 2 , Lilas Tarnus 2 , Makheni Jean Pierre 1 , Mohammed Daira 2 , Cristian Apetrei 2 , Jason Brenchley 1 , Ivona Pandrea 2 1 National Institutes of Health, Bethesda, MD, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: Although numerous co-morbidities such as diabetes, obesity, and pulmonary disorders like COPD are known to enhance the risk of severe COVID-19, dietary influences on disease outcome have not been thoroughly studied. Diets high in sugar and fat associate with several co-morbidities and have been shown to enhance disease in a chronic viral infection, SIV, but have not been investigated for an impact on the acute viral infection SARS-CoV-2. In this study we examine the impact of diet on pathology and immune responses to SARS-CoV-2 infection. Methods: Pigtail macaques (3M, 3F) were fed a commercial monkey chow, then provided a high fat and sugar chow (high fat diet, HFD) for approximately two months preceding SARS-CoV-2 infection (Delta stain). HFD was maintained during infection until euthanasia at day 30-32 of SARS-CoV-2. Three control pigtail macaques (2M, 1F) were infected with the same SARS-CoV-2 strain and dose, and maintained on a commercial monkey chow diet until euthanasia at day 30. Results: Viral RNA (vRNA) was detected for up to 28 days post-infection in nose swabs of both control and HFD macaques, with mean viral loads highest at day 2 and declining thereafter. Mean viral loads were higher at all time points assessed in animals fed a HFD vs. controls, with area under the curve (AUC) of the HFD animals more than 100 times greater than controls (6.6x10 10 and 1.6x10 8 , respectively). Subgenomic RNA (sgRNA, indicating viral replication) was greater in HFD animals as well, with AUC 1.1x10 10 vs. 2.7x10 . Shedding of vRNA in stool was greater in animals fed HFD, with higher AUC and detectable vRNA for a longer duration. Rectal biopsies indicated decreased B cell frequency

following SARS-CoV-2 infection in both control and HFD animals, however significantly lower B cell frequencies were observed between baseline and approximately two months following HFD administration (p=0.03, Wilcoxon). B cell loss was coupled with significant T cell expansion during HFD administration (p=0.03, Wilcoxon), then frequencies declined modestly following infection. Conclusion: SARS-CoV-2 infection can induce lymphopenia, and our sampling of gut mucosal tissue indicates B cell depletion with a HFD that is further exacerbated by SARS-CoV-2 infection, as well as greater shedding of vRNA in both GI tract and respiratory tracts of animals fed a HFD. Excess dietary fat and sugar may disrupt gut barrier integrity and immunity, in turn predisposing the tissue to pathology during viral infection. Impact of COVID-19 Progression in Patients With Hypertension Alba Sanchez 1 , Silvia Chafino 1 , Graciano García-Pardo 1 , Frederic Gómez Bertomeu 1 , Miguel López-Dupla 1 , Antoni Del Pino-Rius 2 , Montserrat Olona 1 , Francesc Vidal 1 , Anna Rull 1 , Joaquim Peraire 1 1 Hospital Universitario de Tarragona Joan XXIII, Tarragona, Spain, 2 Rovira i Virgili University, Tarragona, Spain Background: Coronavirus disease (COVID-19) due to SARS-CoV-2 infection is aggravated by some comorbidities, with arterial hypertension being one of the most common. Hypertensive patients are more vulnerable to developing severe COVID-19 complications through different joint mechanisms. The main objective is to find biomolecules and metabolic pathways through a multiomic approach that may explain the relationship between hypertension and unfavourable COVID-19 disease progression. Methods: One hundred and three patients with COVID-19 were classified according to disease severity (mild, severe and critical) and divided into hypertensive (n=26) and non-hypertensive (n=77). Serum samples were collected at the time of admission (acute phase) and four to eight weeks later (recovery phase), and multiomics studies of proteins, lipids and metabolites were performed. Statistical analyses were carried out by Metaboanalyst 5.0 and SPSS Statistics 25.0. Results: Hypertension was present in 25.2% of COVID-19 patients as a previous comorbid disease. Hypertension was significantly related to COVID-19 severity (p=0.008), in fact, 84.6% of the hypertensive patients belonged to the unfavourable COVID-19 group (severe and critical). The profile of biomolecules changed depending on the study phase, with the number of significant molecules in the acute phase (n=43) greater than those in the recovery phase (n=25). In the acute phase, myo-inositol (AUC=0.695), phosphatidylcholine 32:1 (AUC=0.643) and gelsolin (AUC=0.696) were best able to distinguish between hypertensive and non-hypertensive patients and in the recovery phase, gelsolin (AUC=0.674), zinc-alpha-2- glycoprotein (AUC=0.711) and octanoic acid (AUC=0.699) presented the best discriminatory power. Notably, relative abundance (mean±SD) of gelsolin decreased with COVID-19 severity (mild=1.082±0.622, unfavourable=0.763±0.367) (p=0.002) but increased in unfavourable patients with hypertension (0.919±0.388) compared to non hypertension (0.681±0.332) (p=0.03) in the acute phase. Conclusion: The results confirmed hypertension as a frequent comorbid disease in patients with unfavourable COVID-19 progression, which significantly increases the severity of the disease. Gelsolin, myo-inositol and lipids were those molecules that could be determinants in COVID-19 progression and could explain the clinical worsening of COVID-19 patients through different pathways such as immune system processes, inflammation, oxidative stress and lipid metabolism. SARS-CoV-2 Evolution, Reinfection, and Sustained Viremia in Cancer Patients Juliana D Siqueira , Livia R. Goes, Brunna M. Alves, Marianne M. Garrido, João P. Viola, Marcelo A. Soares Instituto Nacional de Cancer, Rio de Janeiro, Brazil Background: Several studies with longitudinal follow-up on SARS-CoV-2 infection have been reported. Most of them focus only on cases with suspected reinfection or prolonged infection in immunosuppressed individuals. Herein, we describe 26 different cases of SARS-CoV-2 infections in cancer patients with multiple longitudinal samples analyzed and described the different scenarios of sustained viremia, reinfection and viral evolution. Methods: Cancer patients followed at Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil, with more than one SARS-CoV-2 nasopharyngeal swab RT-PCR-positive test from April to August 2020 were included. Viral

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CROI 2024