Summary:
During the COVID-19 pandemic, some individuals reported persistent symptoms weeks or months after acute infection with SARS-CoV-2. As the pandemic developed, it became clear that incomplete recovery was occurring, including in people who initially had mild or even asymptomatic infection. SARS-CoV-2 is a complex condition affecting numerous organ systems. Reported symptoms commonly include fatigue, breathlessness, cough, chest discomfort, headaches, palpitations, muscle pain, cognitive difficulties, and mental health concerns. Symptoms may fluctuate or relapse over time. Persistent symptoms are referred to as long COVID. This study is a narrative review that explores the biological mechanisms thought to underlie long COVID and explains how SARS-CoV-2 causes acute disease. The virus enters human cells by binding to receptors, particularly in the respiratory tract. Infection activates the immune system and promotes cytokine production. In more severe cases, a dysregulated immune response can lead to excessive inflammation, sometimes described as a cytokine storm, contributing to acute respiratory distress and multi-organ dysfunction. Inflammation appears central to both acute COVID-19 and long COVID. Oxidative stress is identified as another important mechanism, and inflammation and oxidative stress may amplify one another, sustaining tissue damage beyond the acute infection phase. Mast cell activation is also discussed as a contributor to ongoing inflammation and immune dysregulation. The review highlights that long COVID likely arises from interacting processes including immune dysregulation, chronic inflammation, oxidative stress, mitochondrial dysfunction, dysbiosis and mast cell activation. The authors discuss natural therapies that could potentially target these mechanisms. These include: supplementation with vitamin D, zinc, coenzyme Q10, alpha-lipoic acid, acetyl-l-carnitine, N-acetylcysteine, vitamin C, flavonoids like quercetin and luteolin, and adaptogens such as ginseng, rhodiola, and schisandra. Probiotics, synbiotics, and fecal microbiota transplantation are also suggested to support gut health. Additionally, lifestyle interventions such as exercise, hydration, breathing exercises, acupuncture, and vagus nerve stimulation may support autonomic function and reduce fatigue. Understanding these overlapping mechanisms and the potential role of natural therapies is considered important for guiding future research and informing therapeutic approaches, though the condition remains incompletely understood.
Abstract:
Post-acute COVID-19 syndrome, or long COVID, now affects millions of people all over the world. Symptoms may be far-reaching and impact almost any system of the body. While some people experience mild symptoms, others may have a more debilitating clinical picture. While our understanding of the mechanisms involved in long COVID has grown over the past few years since the onset of the pandemic, a greater variety of treatment options is still needed. This article discusses underlying mechanisms involved in long COVID pathogenesis and natural therapies that may address these mechanisms.
Article Publication Date: 13/01/2026
DOI: 10.1177/15347354251408959
