Long COVID: Integrating Evidence on Multisystem Manifestations, Mental Health Outcomes, and Quality-of-Life Impacts

Abstract—Long COVID (post-acute sequelae of SARS-CoV-2 infection, PASC) is a complex health challenge marked by persistent, relapsing, multisystem symptoms beyond the acute phase. It affects physical, cognitive, and psychological domains across age groups and severities, straining healthcare systems. This review seeks to compile and critically evaluate available evidence on long COVID, with special emphasis on risk factors, clinical manifestations, diagnostic complexity, mental health outcomes, and management strategies. The aim is to provide an integrated perspective to guide clinicians, researchers, and policymakers in addressing the broad and evolving challenges posed by long COVID. Eligible studies included cohort analyses, cross-sectional surveys, qualitative interviews, systematic reviews, guidelines, and policy documents, selected for relevance to symptoms, mental health impact, diagnostic criteria, risk factors, and management. Long COVID presents highly heterogeneous, often relapsing symptoms across multiple organ systems, including fatigue, respiratory and cardiovascular issues, gastrointestinal disturbances, musculoskeletal pain, and dermatologic changes. Mental health impacts—such as anxiety, depression, PTSD-like symptoms, sleep disturbances—are major drivers of reduced quality of life. Diagnostic challenges arise from symptom overlap and inconsistent definitions, while risk factors include age, sex, comorbidities, socioeconomic status, and acute illness severity. Long COVID imposes a sustained, multidimensional burden. Addressing it requires clearer diagnostic criteria, consistent definitions, integrated care models including mental health and social support, and prevention strategies like vaccination. Coordinated research is essential to identify mechanisms, modifiable risk factors, and effective, equitable management to reduce long-term impacts and health inequities.