Clinical practice guideline for long COVID prevention and treatment, 2026, Cao et al.

[SNT Gatchaman]

Clinical practice guideline for long COVID prevention and treatment

Spoiler: Authors

Bin Cao; Joan B Soriano; Quanyi Wang; Ziyad Al-Aly; Xiaoying Gu; Guiqiang Wang; Yee-Sin Leo; Yang Jin; Qianling Shi; Norio Ohmagari; Enmei Liu; Roger Paredes; Hongzhou Lu; Eu Suk Kim; Dingyu Zhang; Janne Estill; Li Li; Karen Spruyt; Weizhong Yang; Yanjiang Wang; Maosheng Ran; Xufei Luo; Hui Zhang; Jiuyang Xu; Rongling Zhang; Jungang Zhao; Junxian Zhao; Rachael A Evans; Jaehyun Jeon; Michael J Peluso; Lee E Errett; Wenhong Zhang; James D Chalmers; Yaolong Chen

BACKGROUND
This guideline aims to address key clinical questions of long COVID, and to provide evidence-base 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.

METHODS
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 area 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 the 8 PICO 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 Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to rate the certainty of evidence and determine the strength of recommendations.

RESULTS
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 multi-species probiotics, cognitive behavioral therapy (patients with fatigue), and personalized rehabilitation after excluding post-exertional malaise for long COVID treatment.

CONCLUSIONS
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.

Web | DOI | PDF | European Respiratory Journal | Open Access

 

[SNT Gatchaman]

PICO question 7: In patients with long COVID, should cognitive behavioral therapy be used versus no cognitive behavioral therapy?

CBT, a therapeutic approach centered on modifying cognitive patterns and behaviors, has shown potential in alleviating certain symptoms associated with long COVID by reshaping cognitive frameworks, improving emotional regulation, and promoting behavioral activation. However, current evidence was limited, with studies featured small sample sizes, inconsistent outcome measures, and a lack of large-scale RCTs. Our meta-analysis showed high heterogeneity across studies, with most outcomes showing non-significant improvements supported by low-certainty evidence.

Fatigue was the only symptom for which CBT demonstrated statistically significant benefits. Notably, current assessment tools largely focus on somatic symptoms and functional limitations, potentially neglecting cognitive and social dimensions of mental fatigue. These tools are subject to bias and often fail to clearly distinguish between physical and mental fatigue. In addition, while CBT shows potential for anxiety, depression, and social functioning in patients with long COVID, its overall effectiveness remains inconclusive and requires further validation through robust clinical trials.

[…] this guideline suggests CBT as an adjunctive therapy, particularly for patients who do not respond adequately to pharmacological treatments. From a safety perspective, CBT is a non-pharmacological intervention with a favorable risk profile. No serious adverse events have been reported.

Despite these limitations, CBT remains a promising therapeutic option for long COVID patients, particularly those experiencing prominent fatigue and psychological symptoms, due to its potential benefits and low risk of harm.

 

[SNT Gatchaman]

PICO question 8: In patients with long COVID, should rehabilitation exercise be used versus no rehabilitation exercise?

Rehabilitation exercise is a key component of long COVID management for patients without PEM. SRs included in this guideline indicate that rehabilitation interventions may improve physical capacity and quality of life in long COVID patients. However, the magnitude of benefit is generally modest, and the certainty of most evidence is low to very low.

Based on current evidence, we suggest that patients with long COVID should receive personalized rehabilitation training under the guidance and supervision of healthcare professionals, particularly those with a history of hospitalization for COVID-19 or symptoms that significantly affect activities of daily living and functional status. […] Patients with PEM or post-exertional symptom exacerbation (PESE) often demonstrate limited tolerance to rehabilitation training. In such cases, the main focus should be on activity management (rest/pacing) rather than physical exertion. More researches on this topic are needed.

 

[SNT Gatchaman]

Since posting the web link hits a page not found.

The DOI now seems to resolve to

https://publications.ersnet.org/content/erj/early/2026/03/05/1399300302611-2025

previously

https://publications.ersnet.org/content/erj/early/2026/03/05/13993003.02611-2025

with a dot in the last path component before the hyphen. The dot version matches the DOI so I'll leave this as an addendum in case it gets changed again. The DOI should work regardless. The web URL is an early style so will likely change again in time anyway.

 

[Sean]