Long-term SARS-CoV-2 Persistence in Syrian Hamsters

Studies on SARS-CoV-2 viral persistence in a transgenic mouse model and the impact of supplier origin gut microbiomes on disease outcomes

This study assesses the effects of two distinct, murine gut microbiome profiles on acute and post-acute outcomes of SARS-CoV-2 infection and highlights the utility of running wheels for monitoring health status in infectious disease studies and their potential as a behavioral assay in high containment settings.

SARS-CoV-2 ORF8 modulates the upper respiratory tract inflammatory response to facilitate transmission

The infant mouse model is used to define the role of the accessory protein ORF8 in SARS-CoV-2 spread and reveal how a SARS-CoV-2 accessory protein can exploit mucosal antiviral responses to increase host contagiousness.

Intravenous immunoglobulin recalibrates monocyte responses to abortive SARS-CoV-2 infection across viral variants.

Monocytes contribute to inflammation during coronavirus disease 2019 (COVID-19), yet their capacity to support productive infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of viral evolution on their responses, remain unclear. Here, we investigated the interaction between primary human monocytes and three SARS-CoV-2 variants representing distinct evolutionary stages (Wuhan, Delta, and Omicron), and evaluated the modulatory effects of intravenous immunoglobulin (IVIg). All variants efficiently entered monocytes and persisted as intracellular viral RNA and protein, but failed to generate infectious progeny, indicating abortive infection. Despite the absence of productive replication, infected monocytes exhibited marked ultrastructural remodeling and mounted robust innate immune responses. Omicron infection was associated with enhanced replication-related signatures compared with Wuhan and Delta. IVIg did not prevent viral entry or RNA persistence but significantly reduced infection-induced vacuolization and selectively modulated cytokine responses. Notably, high-dose IVIg enhanced TNF-associated responses and reduced IL10 expression, suggesting a recalibration of monocyte inflammatory set-points. These effects occurred independently of neutralizing activity. Together, these findings identify primary human monocytes as targets of abortive yet immunologically active SARS-CoV-2 infection and demonstrate that IVIg modulate monocyte stress and inflammatory responses through Fc-dependent mechanisms rather than direct viral neutralization.

Virus reactivation in acute and long COVID-19

Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness1. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood2, 3, 4, 5, 6–7. Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes. Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute COVID-19 and long COVID. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID. Chronic reactivation of distinct herpesviruses and anelloviruses occur during acute and long COVID-19, and track with disease severity, inflammation and outcomes, revealing immune signatures with prognostic potential.

Persistent expression of myeloid lineage markers in resident and circulating T cells induced by SARS-CoV-2 infection 2328943

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Impaired and dysregulated host immunities, such as impaired coordination and disruption of CD4/CD8 T-cell-mediated virus-specific adaptive immune responses to SARS-CoV-2, have been hypothesized as age-related risk factors in COVID-19 disease severity. However, the characteristics and heterogeneity of CD4/CD8 T cell subsets that respond to SARS-CoV-2 remain elusive. In the present study, we focused on investigating those subsets and there role in COVID-19 infection. We established an age-dependent COVID-19 model by infecting middle-age mice (7-8 months old) or young mice (6-8 weeks old) with 100 or 500pfu of a mouse adapted SARS-CoV-2 virus (SARS2-N501YMA30). Lung, spleen tissues and blood harvested at 60 and 90 days post infection (dpi) were subjected to flow-cytometry and CyTOF for CD4/CD8 T cell profiling. Data was analyzed using FlowJo_v10.10.0 software. Only middle-age mice showed an average weight loss of 10% and 20% in low (100pfu) and high (500pfu) viral dose infected group respectively. Immune profiling revealed increase in the CD11b, CD11c expressing CD4/CD8 T cell subsets in the infected mice. These infection-prompted subsets increased significantly in middle-age mice and were found to contribute in effector functions as well as consist T cell-mediated immune memory, characterized by higher Granzyme B and Perforin expression. This study characterizes CD11b, CD11c expressing CD4/CD8 T cell subsets with potent antiviral effects, which is in accord with the reported data of association of CD11b and CD11c T cell with increased cytotoxic activity in other viral infections like Influenza, RSV. Further analysis of these immune cells is underway to better understand their roles in driving protective or pathogenic immune responses upon SARS-CoV-2 infection in mice. Functional Microbiomics, Inflammation and Pathogenicity- COBRE pilot grant (OGMB220226F1) (JZ); UofL starting package (F1256, F1260) (JZ) Viral Immunology (VIR)

Complex intra-host SARS-CoV-2 evolution following monoclonal antibody pre-exposure prophylaxis