SARS-CoV-2 persistence has been proposed as a potential contributor to the pathogenesis of long COVID, with reservoir tissues potentially serving as sites for viral persistence, intra-host evolution, and intermittent viral shedding. Here, we used experimentally infected Syrian hamsters to investigate long-term SARS-CoV-2 persistence across tissues, viral infectivity, and associated immunological and metabolic alterations. Syrian hamsters (Mesocricetus auratus) were intranasally infected with a SARS-CoV-2 parental strain or Gamma and Delta variants and monitored for up to one year, with samples collected at 3, 15, 30, 90, 150, and 365 days post-infection (dpi). During the acute phase, infected animals exhibited significant weight loss, viral shedding, and marked pulmonary inflammation, accompanied by increased expression of pro-inflammatory cytokines at 3 dpi. Infection was confirmed by seroconversion, with sustained IgG responses and low-titer neutralizing antibodies against Omicron. Viral nucleoprotein was detected in multiple tissues up to 365 dpi, while RT-qPCR identified persistent low-level viral RNA in the lungs, brain, spleen, and thymus throughout the observation period, without evidence of productive viral replication. Immune gene expression displayed organ-specific temporal patterns: acute pulmonary inflammation transitioned into broad late-stage suppression, except for sustained TGF-β expression; the brain exhibited a late chemokine signature at 365 dpi; and the thymus showed a delayed immune activation peak at 150 dpi, particularly in Delta-infected animals. Metabolomic profiling revealed a shared acute-phase metabolic signature across variants that largely resolved by 365 dpi, whereas Delta-infected animals retained distinct residual metabolic alterations. Collectively, these findings establish a model of long-term SARS-CoV-2 tissue persistence characterized by organ-specific immune and metabolic signatures, providing a platform to investigate mechanisms underlying post-acute sequelae and evaluate potential therapeutic strategies." />
Long-term SARS-CoV-2 Persistence in Syrian Hamsters | bioRxiv
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Long-term SARS-CoV-2 Persistence in Syrian Hamsters
View ORCID ProfileThais Melquiades de Lima, Carlos Eduardo Capelini Eli Lopes, Maria Vitoria Oliveira de Souza, Felipe Rocha do Nascimento, Daniela Meria Ramos Rodrigues, Gabriela Conde Silva, Matheus Dias, Tufi Antonio Nasser Neto, Maria Lucia Silva, Daniel Macedo de Melo Jorge, Juliano de Paula Souza, Eurico Arruda
doi: https://doi.org/10.64898/2026.07.19.739454
Thais Melquiades de Lima
University of Sao Paulo
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Carlos Eduardo Capelini Eli Lopes
University of Sao Paulo
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Maria Vitoria Oliveira de Souza
University of Sao Paulo
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Felipe Rocha do Nascimento
University of Sao Paulo
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Daniela Meria Ramos Rodrigues
University of Sao Paulo
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Gabriela Conde Silva
University of Sao Paulo
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Matheus Dias
University of Sao Paulo
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Tufi Antonio Nasser Neto
University of Sao Paulo
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Maria Lucia Silva
University of Sao Paulo
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Daniel Macedo de Melo Jorge
University of Sao Paulo
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Juliano de Paula Souza
University of Sao Paulo
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Eurico Arruda
University of Sao Paulo
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Abstract<br>SARS-CoV-2 persistence has been proposed as a potential contributor to the pathogenesis of long COVID, with reservoir tissues potentially serving as sites for viral persistence, intra-host evolution, and intermittent viral shedding. Here, we used experimentally infected Syrian hamsters to investigate long-term SARS-CoV-2 persistence across tissues, viral infectivity, and associated immunological and metabolic...