[Comment] Negative results in long COVID clinical trials: choosing outcome measures for a heterogeneous disease

Long COVID is an umbrella term for the heterogeneous long-term consequences of SARS-CoV-2 infection. It encompasses a wide spectrum of phenotypes (sometimes overlapping), and its underlying mechanisms might vary across and within phenotypes. Trials that do not account for this heterogeneity risk false-negative results. First, endotypic heterogeneity might produce heterogeneity in treatment response, and inadequate methodologies risk eclipsing responder subgroups. Second, and the focus herein, phenotypic heterogeneity constitutes a challenge for the choice of outcome measures.