Clinical practice guideline for long COVID prevention and treatment

This guideline aims to address key clinical questions of long COVID, and to provide evidence-based recommendations. The target population is adults with long COVID. The primary users of the guideline are clinical physicians, clinical pharmacists, nurses and general practitioners in community healthcare institutions worldwide.

The guideline was registered at the Practice guideline REgistration for transPAREncy platform (PREPARE-2024CN123) and followed a pre-specified protocol. A multidisciplinary working group was established and comprised 60 members from 10 countries and 10 areas of expertise, with a strong background in long COVID research and clinical practice, and methodology of guideline development. Through a two-step process, we determined eight PICO (Population, Intervention, Comparator, Outcome) questions focusing on prevention and treatment of long COVID. After comprehensively searching literature, conducting systematic reviews and investigating patients' values and preferences, three rounds of Delphi survey were conducted among 24 international experts to reach consensus. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was applied to rate the certainty of evidence and determine the strength of recommendations.

The guideline presents 10 specific recommendations, each supported by existing, updated or newly conducted systematic reviews. The key recommendations are pertinent to the following issues: 1) suggestion of vaccination or use of antiviral agents during the acute phase of COVID-19 to prevent long COVID; 2) suggestions against the use of nirmatrelvir/ritonavir and glucocorticoids (patients with persistent respiratory symptoms and olfactory disorders) for long COVID treatment; 3) suggestions supporting the use of multispecies probiotics, cognitive behavioural therapy (patients with fatigue), and personalised rehabilitation (after ruling out post-exertional malaise) for long COVID treatment.

This guideline provides evidence-based recommendations for the prevention and treatment of long COVID. Given the limited and often low-methodological-quality evidence, all recommendations are supported by very low to moderate certainty. Further high-quality studies are needed to strengthen the evidence base.