CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: The median follow-up time for immunocompromised patients was longer than for the controls (6 days vs. 4 days, respectively). Immunocompromised patients and controls were mainly infected by Omicron BA.1. Univariate analyses of the emergence of minor mutations showed an overexpression of 5 mutations in immunocompromised patients and the absence of minor mutations in the control group at the end of the follow up period: N:R13C, ORF1ab:L896S, ORF1ab:N5591K, ORF1ab:P557T and the N:136delG deletion (see figure). Multivariate analyses confirmed the impact of immunodeficiency status on the emergence of these mutations (N:136delG p<0.01, N:R13C p<0.01, ORF1ab:L896S p<0.05, ORF1ab:N5591K p<0.01, ORF1ab:P5557T p<0.01). These mutations were observed in patients infected with clades BQ.1 and BA.5. Conclusions: The univariate and multivariate analyses suggested a greater genetic diversity, which increased over time in immunocompromised patients. Isolated mutations in N and ORF1ab gene could affect protein structure therefore an in-silico and in-vitro approaches could be interesting to investigate the effect on protein structure.

higher than lost ones in all comparisons. In T1 vs . T2 the acquisitions were prevalent in the S gene and the losses in ORF1a, in T2 vs. T3 the opposite was observed.Significant mutations disappearing was observed in all genes in BA.1 ( p <.0001), while in XBB variant a significant mutation emerging was detected in ORF1a, ORF1b and S genes ( p =.016). Subjects with cardiovascular disease showed a significant acquisition of mutations over time ( p =.048). Conclusions: Our data suggested a mechanism of 2-step fitness selection of SARS-CoV-2 mutations. The first step indicated that genetic diversity increases during the first week of viral infection. In the second week a purifying selection process was observed. A further increase in new mutations was observed at week 3. Prevalence, Spread, and Mutation of SARS-CoV-2 Variants in COVID-19 Testing in Salvador, Brazil Anna Carolina Dantas 1 , Hellen B. M. Oliveira 1 , Taiana Tainá S. Pereira 2 , Amanda F. Lima 1 , Janaína M. F. Matos 1 , Thais Aranha Rossi 1 , Laio Magno Santos de Sousa 1 , Fabiane Soares 1 , Ines Dourado 1 , Thiago Silva Torres 3 , Luciane A. Amorim Santos 4 , Danielle S. Medeiros 1 , Fernanda K. Barreto 1 , Guilherme G. Campos 1 , Lucas M. Marques 1 1 Federal University of Bahia, Salvador, Brazil, 2 Universidade de São Paulo, São Paulo, Brazil, 3 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil, 4 Fundação Oswaldo Cruz, Rio de Janeiro, Brazil Background: Genomic sequencing plays an essential role in the ongoing monitoring of SARS-CoV-2 genome evolution, as phylogenetic analyses can identify genomic signatures of circulating strains, thus helping to track transmission or spreading events. By understanding the spread of SARS CoV-2, public health strategies can be deployed (at various levels) to reduce new infections and mitigate the impact of the pandemic. The study aimed to investigate the prevalence and genomic spread of SARS-CoV-2 variants in a study focused on expanding COVID-19 testing, quarantine, and telemonitoring strategies (TQT-COVID-19 Project). Methods: A total of 177 samples collected between July 2022 and April 2023 from users of 17 Primary Health Care (PHC) units in Salvador, Bahia, were analyzed. The samples were sequenced using Oxford Nanopore MinION technology and analyzed through bioinformatics for variant typing and genomic spread assessment. Results: The majority of participants were women (68.9%), under the age of 39 (50.6%), used public transportation (66.5%), and had no comorbidities (66.5%). Most presented mild COVID-19 symptoms (41.5%) and had received the second booster dose of the vaccine (40.6%). The most prevalent Omicron subvariants were BA.5 (32.57%), BA.4 (21.71%), B (18.86%), and BQ.1 (26.2%). However, other variants, such as XBB, were also identified. The virus spread predominantly in a controlled and localized manner, with low dissemination. However, sporadic events of rapid spread were identified, possibly linked to inter-municipal travel, superspreader events, or containment failures. Upon mutation analysis, vaccinated individuals presented a consistent accumulation of mutations in the spike protein, whereas unvaccinated individuals showed a different set of mutations. Conclusions: This study observed the circulation of multiple lineages and several introduction events of new variants over time. Identifying and understanding these events may help develop more targeted intervention strategies to break the chain of transmission. CPSF6 Regulates Cellular Permissivity to HIV-1 Infection Through Alternative Polyadenylation Daphne Cornish 1 , Kathryn A. Jackson-Jones 1 , Ted Ling Hu 1 , Lacy M. Simons 1 , William J. Cisneros 1 , Edmund Osei Kuffour 2 , Francesca Agnes 1 , Yujin Lee 1 , Paul Bieniasz 2 , Ramon Lorenzo-Redondo 1 , Judd F. Hultquist 1 1 Northwestern University, Chicago, IL, USA, 2 The Rockefeller University, New York, NY, USA Background: Cleavage and polyadenylation specificity factor 6 (CPSF6) is a host factor that is recruited to HIV-1 capsid cores and plays a multifaceted role in the viral replication cycle. CPSF6 knock-out phenotypes in cell lines are highly variable, leading to continued debate surrounding the role of CPSF6 in HIV-1 infection. Outside of HIV-1 infection, CPSF6 plays a role in mRNA processing and poly(A) site selection as a member of the CFIm complex. Disruption of CPSF6 function leads to altered poly(A) site selection through a process known as alternative polyadenylation (APA), resulting in usage of proximal poly(A) sites and shortening of 3’ UTRs. We hypothesize that disruption of CPSF6 function,

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SARS-CoV-2 Intra-Host Evolution During Acute Infection in People With COVID-19 Carla della Ventura 1 , Annalisa Bergna 1 , Cosmin L. Ciubotariu 1 , Haneen Chmes 1 , Mario C. Corbellino 1 , Agostino Riva 2 , Spinello Antinori 2 , Gianguglielmo Zehender 1 , Alessia Lai 1 1 Universita di Milano, Milan, Italy, 2 Luigi Sacco University Hospital, Milan, Italy Background: Intra-host evolution reflects a general mechanism for the continued emergence of novel highly divergent SARS-CoV-2 variants. The intra-host evolution of SARS-CoV-2 was investigated with the aim of assessing conditions associated with the acquisition of new viral mutations through the sequencing of viral genomes. Methods: 58 cases of COVID-19 with 2 or more longitudinally positive SARS CoV-2 swabs collected at intervals of at least 7 days from the first positive swab in the period 2021-2023 were analysed. All samples were subjected to whole genome sequencing with next-generation procedures. Results: The median age was 83 years (IQR:73-88) and 55% were males.57 were hospitalized for a median of 23 days (IQR:16-32), and 12 died (21%) after a median of 25 days (IQR:19-34). No one reported previous SARS-CoV-2 infection; 79% were vaccinated.23% received more than one treatment for SARS-CoV-2 infection. Negativization period showed longer intervals in BQ.1 (39 days) and shorter in BA.1 infections (17 days, p =.04). No drug resistance mutations were observed over time.In T1 vs. T2 38% decreased/increased number of mutations and 24% maintained the same number. Subjects with constant numbers of mutations maintained the same pattern while 50% of the acquisitions and losses were confirmed. Acquired mutations at T2 were not present as minority mutations at T1, 50% of the lost mutations did not persist at T2.In T2 vs. T3, 67% and 33% increased or maintained the same number of mutations, respectively. 75% of subjects with constant number of mutations maintained the same pattern, 50% of the acquisitions were confirmed. New mutations at T3 were not present as minority mutations at T2.Globally total number of acquired mutations were

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CROI 2025