Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies

Abstract

Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.