Operationalisation of post-COVID condition case definition in a comprehensive research protocol

Background and purpose: Post-COVID-19 condition (PCC) is a prevalent and high-burden sequela of SARS-CoV-2 infection. Because of the complexity of its manifestations, PCC case definition currently lacks standardisation and reproducibility. We aimed to devise a simple screening tool to boost reproducibility and comparability of PCC case definition across PCC studies, and to provide a framework in which to reliably identify suspected PCC cases. We also developed a comprehensive assessment protocol based on the most frequently reported PCC characteristics. Methods: Within a European multi-centre study and based on the conclusions of a previous systematic review, we devised a checklist to assess the presence of PCC-associated symptoms and their temporal relationship with COVID-19. Results: The checklist was developed to include three symptom cores (cognitive, psychiatric, and general). For each symptom, onset is assessed within 3 months after COVID-19 resolution and persistence for at least 2 months. Any symptom fulfilling this criterion is sufficient to prompt suspicion of PCC. At least one symptom is required in the cognitive or psychiatric domains to suspect PCC with neuropsychiatric involvement. Our protocol features an extensive neuropsychological evaluation and self-administered scales for mood, anxiety, stress-related symptoms, sleep disorders, quality of life, disability, mental health, and personality traits; scales for quantitative assessment of fatigue and headache are also included. Conclusions: Consistent identification of PCC cases is crucial to correctly include patients in research and clinical studies. We propose a simple, reproducible, and flexible screening tool and a proposal for a comprehensive assessment that could be employed to enhance standardisation and comparability.