Methodological quality and clinical applicability of long COVID guidelines and scientific statements: a systematic review using AGREE II and AGREE-REX.

Abstract

Long COVID is projected to affect 0.6 to 1.0% of the population between 2025 and 2030. This study reviewed the methodological quality, clinical applicability and content of the care recommendations issued for adults ≥18 years with long COVID in clinical practice guidelines (CPGs) and scientific statements (SSs). Registered in PROSPERO (CRD420261324906). PubMed, Scopus, trip, five guideline repositories and national health portals were searched between February and April 2026, and PubMed and Scopus were updated on 2 September 2026. Eligible documents were CPGs and SSs on adults with suspected or confirmed long COVID, published in English or Spanish. Screening and full-text review were duplicated independently; data were extracted by one reviewer and verified by a second. Methodological quality was appraised with AGREE II, reporting the six standardised domain scores separately, each rescaled within its domain and never summed into an overall score; applicability was appraised with AGREE-REX. A narrative synthesis covered five predefined care domains. Twenty documents were appraised, 19 from the initial search and one from the update. From the 19 initial documents, 510 recommendations were extracted across five NICE-derived domains, mostly clinical management (63.3%) and care planning (29.6%). Quality was uneven (rigor of development 16.7-97.9%; applicability 0.0-95.8%; editorial Independence median 100%), and only one document reported a GRADE-compatible evidence-to-decision framework. Four documents were prioritised and contributed 99 recommendations; they scored higher than the remaining corpus in all six domains, yet applicability remained their weakest (68%). AGREE-REX showed recommendations directed far more clearly at clinicians than at patients or decision-makers. Content converged on shared decision-making, multidisciplinary rehabilitation, patient-centered care and return-to-work support. Guidance on long COVID is abundant but methodologically uneven, and the unevenness is concentrated in how evidence is linked to recommendations and in applicability. The corpus offers well-formulated clinical content whose evidence-to-decision reasoning and implementation requirements are seldom reported, and it therefore requires formal contextual adaptation, for example through GRADE-ADOLOPMENT, before use. Key limitations are the scarcity of guidance from low- and middle-income countries and the diversity of development methods. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261324906, Identifier CRD420261324906.