Long COVID is a multisystem condition that affects at least 10% of severe SARS-CoV-2 infections, with over 65 million individuals globally estimated to have the condition. It is characterized by a wide range of symptoms affecting multiple organ systems, including cardiovascular, thrombotic, and cerebrovascular diseases, type 2 diabetes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia. Symptoms can persist for years, with some conditions expected to be lifelong. Long COVID is associated with all ages and disease severities, with the highest prevalence in individuals aged 36–50 years. Most long COVID cases are in non-hospitalized patients with mild acute illness. Current diagnostic and treatment options are insufficient, and clinical trials must prioritize addressing leading hypotheses. Long COVID is associated with immune dysregulation, including T cell alterations, elevated interferon levels, and autoantibodies. Reactivated viruses such as EBV and HHV-6 are also implicated. Low or absent immune responses in the acute phase of infection are predictive of long COVID. Autoantibodies are inversely correlated with protective antibodies, suggesting a higher risk of breakthrough infections. SARS-CoV-2 viral rebound in the gut is associated with lower levels of receptor-binding domain IgA and IgG antibodies. There are significant differences in antibody production, seroreversion, and antibody titre levels across the sexes, with women being less likely to seroconvert and more likely to serorevert. Long COVID is associated with vascular issues, including endothelial dysfunction, microclots, and reduced vascular density. It increases the risk of cardiovascular diseases, including heart failure, dysrhythmias, and stroke. Multi-organ damage is common, with 70% of 201 patients showing damage to at least one organ. Long COVID is also associated with neurological and cognitive symptoms, including memory loss, cognitive impairment, and paresthesia. These symptoms are often debilitating and may persist for years. Long COVID is also associated with dysautonomia, particularly postural orthostatic tachycardia syndrome (POTS), and is often comorbid with ME/CFS. Long COVID in children is common, with symptoms including fatigue, headache, dizziness, and shortness of breath. It is associated with liver injury and increased risks of acute pulmonary embolism, myocarditis, and cardiomyopathy. Long COVID is also associated with reproductive system impacts, including menstrual alterations and ovarian reserve decline. It is also associated with gastrointestinal symptoms, including nausea, abdominal pain, and constipation. The impact of vaccines, variants, and reinfections on long COVID is variable. Vaccination may provide partial protection, with reduced risk of long COVID between 15% and 41%. Reinfections are increasingly common, and multiple infections may increase the risk of long COVID sequelae. LongLong COVID is a multisystem condition that affects at least 10% of severe SARS-CoV-2 infections, with over 65 million individuals globally estimated to have the condition. It is characterized by a wide range of symptoms affecting multiple organ systems, including cardiovascular, thrombotic, and cerebrovascular diseases, type 2 diabetes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia. Symptoms can persist for years, with some conditions expected to be lifelong. Long COVID is associated with all ages and disease severities, with the highest prevalence in individuals aged 36–50 years. Most long COVID cases are in non-hospitalized patients with mild acute illness. Current diagnostic and treatment options are insufficient, and clinical trials must prioritize addressing leading hypotheses. Long COVID is associated with immune dysregulation, including T cell alterations, elevated interferon levels, and autoantibodies. Reactivated viruses such as EBV and HHV-6 are also implicated. Low or absent immune responses in the acute phase of infection are predictive of long COVID. Autoantibodies are inversely correlated with protective antibodies, suggesting a higher risk of breakthrough infections. SARS-CoV-2 viral rebound in the gut is associated with lower levels of receptor-binding domain IgA and IgG antibodies. There are significant differences in antibody production, seroreversion, and antibody titre levels across the sexes, with women being less likely to seroconvert and more likely to serorevert. Long COVID is associated with vascular issues, including endothelial dysfunction, microclots, and reduced vascular density. It increases the risk of cardiovascular diseases, including heart failure, dysrhythmias, and stroke. Multi-organ damage is common, with 70% of 201 patients showing damage to at least one organ. Long COVID is also associated with neurological and cognitive symptoms, including memory loss, cognitive impairment, and paresthesia. These symptoms are often debilitating and may persist for years. Long COVID is also associated with dysautonomia, particularly postural orthostatic tachycardia syndrome (POTS), and is often comorbid with ME/CFS. Long COVID in children is common, with symptoms including fatigue, headache, dizziness, and shortness of breath. It is associated with liver injury and increased risks of acute pulmonary embolism, myocarditis, and cardiomyopathy. Long COVID is also associated with reproductive system impacts, including menstrual alterations and ovarian reserve decline. It is also associated with gastrointestinal symptoms, including nausea, abdominal pain, and constipation. The impact of vaccines, variants, and reinfections on long COVID is variable. Vaccination may provide partial protection, with reduced risk of long COVID between 15% and 41%. Reinfections are increasingly common, and multiple infections may increase the risk of long COVID sequelae. Long