Developing a general research framework for long COVID using causal modelling
摘要
Long COVID is an infection-associated chronic condition with uncertain evolution, leading to ambiguity in case definitions and various hypotheses about its pathophysiology. Despite this diversity, causal models may offer a unified understanding of post-acute COVID-19 mechanisms. This study aimed to examine whether dynamic Bayesian networks could facilitate inferences on long COVID.
MethodsUsing a causal engineering approach, we developed directed acyclic graphs and qualitatively parametrised them as Bayesian networks to depict the hypothesised mechanisms of long COVID in a theory-agnostic manner. Based on the literature and expert knowledge, we created a general modelling framework summarising biological pathways from mild or severe COVID-19 to the development of respiratory symptoms and fatigue over four key periods (t1 to t4). We used qualitative parametrisation for design and validation, and tested the framework against four scenarios: A) mild COVID-19 at t1 (start of acute infection); B) severe acute COVID-19 at t1; C) symptoms reported at t1 (acute COVID-19 disease); and D) symptoms reported at t1 and t3 (e.g., 3-to-6 months post-acute infection), indicating long COVID.
ResultsHere we show that, in scenario A, the probability of progressing to severe disease and developing persistent organ dysfunction 1-to-2 years post-acute COVID-19 was lower than in scenario C. Those reporting symptoms at t1 and t3 have the highest probability of developing persistent organ dysfunction beyond the acute infection period.
ConclusionsOur findings lay the foundations for a better understanding of the progression of long COVID syndromes. Illustrative simulations support the use of causal models to help address both diagnostic and prognostic questions in long COVID research.