A collection of over 3000 independent, full-length SARS-CoV-2 sequences deriving from posited or confirmed chronic infections is assembled and 14 distinct mutation patterns (MPs) that repeatedly appear in these sequences are described, including four CD8 T cell-escape MPs and two MPs that represent adaptation to tissue compartments outside the upper-respiratory tract.
Abstract
The SARS-CoV-2 pandemic has been marked by two outstanding features that have had major impacts on global public health: the repeated emergence and growth of highly divergent saltation variants with no known close relatives and the development of adverse health effects extending beyond the period of acute infection, called long Covid, in a proportion of the population. Chronic infections in immunocompromised hosts are the most likely explanation for the emergence of saltation variants, and some evidence indicates that viral persistence contributes to long Covid. Knowledge of intrahost evolution during prolonged SARS-CoV-2 infection is therefore vital for understanding the global evolution of SARS-CoV-2 and for deciphering the nature of long Covid and promising avenues for treatment. We assembled a collection of over 3000 independent, full-length SARS-CoV-2 sequences deriving from posited or confirmed chronic infections. We describe 14 distinct mutation patterns (MPs) that repeatedly appear in these sequences—each involving mutations in multiple genomic regions—including four CD8 T cell-escape MPs and two MPs that represent adaptation to tissue compartments outside the upper-respiratory tract. The existence of these MPs promises new insights into the life cycle and evolution of SARS-CoV-2 and the nature of persistent SARS-CoV-2 infection.
This study helps to understand the SARS-CoV-2 evolution and dynamics in Niger Republic, where diagnostic capacities and containment measures were challenging.
Adamou Lagaré, Issaka Aboubacar Adakal, A. Yacouba et al.· Infection, Genetics and Evol...· 0 citations
A genome engineering technology is used to change a single amino acid in the viruses’ main protease enzyme to match that of circulating Omicron isolates to demonstrate antiviral efficacy of approved drugs and uncover mutants with reduced drug sensitivity.
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.
Thais Melquiades de Lima, Carlos Eduardo Capelini Eli Lopes, Maria Vitoria Oliveira de Souza et al.· bioRxiv· 0 citations
Susceptibility to SARS-CoV-2 breakthrough infection in those with hybrid immunity is strongly associated with low levels of pre-existing antibody, but the diversity of immune markers associated with protection implies that additional benefits may be conferred by multi-pronged immunity.
A. Singanayagam, H. Wagstaffe, L. J. Slater et al.· medRxiv· 0 citations
Differences in expression and editing patterns of ADARs between critical and non-critical patients are demonstrated, supporting a potential role of ADAR editing in COVID-19 pathogenesis.
Aiswarya Mukundan Nair, H. Piontkivska· International Journal of Mol...· 0 citations
Tracking SARS-CoV-2 variants revealed the predominance of the JN.1 sublineage of Omicron with generally mild symptoms, highlighting the need for robust, ongoing genomic surveillance integrated with epidemiological data to enable early detection of emerging variants and strengthen control strategies.
P. Rao, S. Ganju, Lata R. Chandel· Journal of Clinical and Diag...· 0 citations