Viral persistence in long COVID: Research advances and treatment strategies

Although the coronavirus disease 2019 (COVID-19) pandemic has ended, the enduring health impacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continue to garner global attention, as approximately 10% of patients develop long COVID (post COVID-19 condition). The epidemiological characteristics and symptoms of long COVID have been reported, and various pathogenic hypotheses have been proposed. Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COVID symptoms. This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms, and explores the relationship between viral persistence and other etiological hypotheses, such as immune dysregulation, vascular issues, coagulation dysfunction, microbiome dysbiosis, brainstem/vagus nerve signaling dysfunction, and latent virus reactivation. Futhermore, treatment strategies for long COVID are proposed based on current clinical trials of antiviral and immune modulation therapies. Understanding the role of viral persistence in long COVID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.