Abstract
BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum. OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field. METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward. RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings. CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.