Nasal Streptococcus pyogenes Infection Exacerbates Psoriasiform Relapse in Mice Through TLR2-Dependent Dendritic Cell Metabolic Reprogramming and γδ T Cell Activation.

Long COVID has emerged as one of the major long-term consequences of the COVID-19 pandemic, affecting millions of individuals worldwide and posing a substantial clinical and societal burden years after acute SARS-CoV-2 infection [–]. Although highly heterogeneous in presentation, fatigue consistently represents one of the most prevalent and disabling manifestations, profoundly impairing quality of life, physical functioning, and return to normal daily activities []. Importantly, persistent symptoms frequently occur independently of acute disease severity and may remain detectable long after viral clearance []. Despite the growing burden of long COVID, therapeutic options remain limited, and no approved disease-modifying interventions are currently available []. Over the past few years, the understanding of long COVID has progressively evolved from a poorly defined post-viral condition toward a biologically complex syndrome involving persistent immune activation, metabolic dysfunction, and multisystem alterations [–]. Recent multiomic analyses have further reinforced this concept, identifying persistent inflammatory, metabolic, and immune signatures associated with long COVID recovery trajectories independently of acute disease severity []. In parallel, increasing evidence has implicated the gut microbiota as a potential contributor to long COVID pathophysiology []. Several studies have reported persistent alterations in gut microbial composition and function following SARS-CoV-2 infection, including depletion of health-associated commensals, reduced representation of short-chain fatty acid (SCFA)-producing bacteria, and enrichment of inflammatory microbial signatures associated with symptom persistence [–]. These alterations have additionally been linked to systemic inflammation, fatigue severity, sleep disturbances, neurocognitive symptoms, and impaired quality of life, supporting the hypothesis that coordinated microbiota–immune–metabolic interactions may contribute to long COVID manifestations beyond the gastrointestinal tract [, –]. This emerging framework is particularly relevant in light of the growing overlap between long COVID and other post-infectious chronic conditions, especially myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which share persistent fatigue, post-exertional malaise, neurocognitive dysfunction, immune dysregulation, and altered energy metabolism as common biological and clinical features [–]. Within this context, the microbiota-gut-brain axis has gained increasing attention as a potential mechanistic interface linking microbial dysbiosis, immune signaling, metabolism, and neurological symptoms [].