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Cover of COVID-19 rapid guideline: managing the long-term effects of COVID-19 (NG188)

COVID-19 rapid guideline: managing the long-term effects of COVID-19 (NG188)

Evidence review 5: interventions

NICE Guideline, No. 188

Literature search

NICE’s information services team identified relevant evidence through focused evidence searches between 22 and 28 October 2020 (see search history document). Additional studies were also considered from NICE surveillance up to 28 October 2020. Results from the literature searches and surveillance were screened using their titles and abstracts for relevance against the criteria from the protocol (see appendix 2). Four reviewers screened titles and abstracts. Having identified the evidence, four reviewers assessed the full text references of potentially relevant evidence to determine whether they met the inclusion criteria for this evidence review. All uncertainties were discussed and referred to an adviser if needed. See appendix 4 for the study flow chart of included studies.

To complement this search, the Healthcare Improvement Scotland knowledge management team conducted a search to identify qualitative evidence to support the questions in this review. See Managing the long-term effects of COVID-19: the views and experiences of patients, their families and carers for more information. The search for patient experience evidence identified five qualitative studies relevant to the overall review. The themes emerging from these studies were considered alongside the quantitative evidence and included where appropriate. This review will be referred to in this document as “patient lived experience”.

Review question 5

What pharmacological and non-pharmacological interventions improve the ongoing physical or mental health symptoms and problems carrying out usual activities, including work, education and leisure, following acute COVID-19?

The review protocol is shown in appendix 2.

Included studies

In total 4104 references were identified through the searches. Of these 505 were included and ordered for full text assessment. A total of 58 references were included for the whole guideline, 2 of which were included for this review. No intervention studies were found and the 2 included studies were rapid reviews; 1 rapid living systematic review, and 1 rapid narrative review with practice recommendations for primary care. See table 1.

Table 1. Included studies for review question 5.

Table 1

Included studies for review question 5.

Key results

No primary research studies were identified. A rapid living systematic review (Andrenelli, 2020) also found no evidence on rehabilitation interventions in the post-acute or chronic phases of COVID-19. Low quality evidence from a rapid narrative review (Greenhalgh 2020a) of indirect evidence proposed self-management and medical management interventions for primary care with additional community mental health support, safety netting and referral. The proposed medical management included listening and empathy, and the need for this was reinforced by the patient lived experience evidence, where acceptance and understanding emerged as a prominent theme of importance to many patients. The patient lived experience data further indicated that providing knowledge and understanding of their condition helped people manage their anxiety.

Strengths and limitations

Please note that GRADE is not used for NICE rapid COVID-19 guidelines. Risk of bias assessment is conducted.

Due to the novelty of the topic and the sparseness of the evidence base, the search was extended to include descriptive and analytic study designs. No primary research studies were identified for the evidence review and this finding was reinforced by the secondary evidence from a rapid living systematic review (Andrenelli 2020), which found no evidence on rehabilitation interventions, and a rapid narrative review (Greenhalgh 2020a) that was limited by indirect evidence from previous coronavirus outbreaks and expert opinion.

Expert panel discussion

This section describes how the expert panel considered the evidence in relation to the recommendations within the guidance.

Relative value of different outcomes

The outcomes the panel expected from the evidence on interventions for the long-term effects of COVID-19 were symptom improvement or worsening, mortality, return to usual activities, quality of life and adverse events. However, in the absence of primary research, none of these outcomes were reported and the secondary evidence was restricted to proposed interventions based on indirect evidence and expert opinion. These interventions informed the panel discussions and reinforced recommendations on management and rehabilitation. Additionally, components of service models that were identified in the related service model evidence review informed the panel’s decision making. The main components advocated by the panel were the use of multidisciplinary teams with specialist expertise, individualised interventions beginning with self-management, and the use of both remote and in-person modes of delivery.

Quality of the evidence

The panel noted the lack of evidence on interventions and therefore largely based its recommendations on its own clinical and lived experience.

Trade-off between benefits and harms

The panel expressed concern over the use of interventions to manage short term symptoms that might cause harm in the longer term, indicating the need for the guideline to advise caution over such interventions, including over the counter medicines.

The panel discussed the ongoing debate over self-pacing and graded forms of exercise. The panel considered careful self-pacing of exercise to be an important element of self-management. However, the panel concluded that in the absence of evidence relating to people with ongoing symptoms from COVID-19 it could not make specific recommendations and it agreed to include a research recommendation to determine the effectiveness of exercise interventions for this population.

The panel stated, from their professional experience, that home pulse oximetry can induce anxiety and may not always be accurate, and therefore advised that it should be accompanied by educational materials to be effective. The panel emphasised the need for differentiation in support to address differing symptoms and circumstances, such as difficulty using digital platforms for people with cognitive problems or accessibility issues.

Implementation and resource considerations

The panel highlighted the current resource constraints of pulmonary rehabilitation services and that post COVID-19 syndrome would require additional resources to fund rehabilitation. The panel also expressed concern over the impact on existing services for other conditions and agreed that resources should not be diverted from these services to new COVID-19 rehabilitation services.

Other considerations

The panel agreed that there is a need for the guideline to acknowledge social and financial factors in supporting patient recovery. The panel highlighted that sources of advice and support should include support groups, social prescribing, online forums and apps. This was supported by patient lived experience evidence, which indicated that patients valued these types of interventions. The panel were aware of the online support service YourCOVIDRecovery. Support from other services was also considered to be important, including social care, housing, employment, and advice about financial support. Based on their own experience, the panel agreed on the value of symptom diaries and symptom tracking apps in self-monitoring.

The panel agreed that multidisciplinary rehabilitation teams should work with people to make a personalised plan for their rehabilitation needs, but they emphasised that rehabilitation planning should only happen after checking for symptoms that would need investigating before the person can safely start rehabilitation. The panel agreed on the potential the value of a multidisciplinary approach to rehabilitation, including fatigue management, breathing retraining, and psychological or psychiatric support.

Appendix 1. Methods used to develop the guidance

Please refer to methods document for details of the methods used to develop the guidance.

Appendix 2. Review protocols

Review question 5: What pharmacological and non-pharmacological interventions improve the ongoing physical or mental health symptoms and problems carrying out usual activities, including work, education and leisure, following acute COVID-19?

PopulationAdults and children who are experiencing new or ongoing symptoms:
  • 4 to 12 weeks from onset of acute COVID-19
  • 12 weeks from onset of acute COVID-19
  • Pharmacological interventions
  • Non-pharmacological interventions
For treatment, management (including self-management and rehabilitation) and support
ComparatorsAny or no comparator
  • Symptom improvement (or worsening)
  • Mortality
  • Return to usual activities including work, education or leisure
  • Resumption of (informal) caring arrangements
  • Quality of life and/or Wellbeing
  • Adverse events (relating to treatment), e.g. side effects or unintended consequences
  • Groups as defined in the EIA for example, age, sex, ethnicity
  • Diagnosis of COVID-19 (e.g., confirmed, or high clinical suspicion)
  • Duration of symptoms
Study types


The following study design types for this question are preferred. Where these studies are not identified, other study designs will be considered.

  • Systematic reviews of RCTs and observational studies
  • RCTs
  • Prospective and retrospective observational studies

Other exclusions
  • Management of acute COVID-19 (symptoms experienced for up to 4 weeks)
  • Management of other conditions with similar features to post-COVID-19 syndrome, for example post-intensive care syndrome and myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome (ME/CFS)
  • Management of end-organ damage, which already has defined pathways of care.

Appendix 3. Literature search strategy

Please refer to the search history record for full details of the search.

Appendix 4. Study flow diagram

Image niceng188er4app4f1

Appendix 5. Included studies

  • Andrenelli E, Negrini F, De Sire A et al Rehabilitation and COVID-19: a rapid living systematic review 2020 by Cochrane Rehabilitation Field. Update as of September 30th, 2020. European journal of physical and rehabilitation medicine [PubMed: 33118719]
  • Greenhalgh, Trisha, Knight, Matthew, A’Court, Christine et al (2020) Management of post-acute covid-19 in primary care. BMJ 370 [PubMed: 32784198]

Appendix 6. Evidence tables

Andrenelli 2020 (PDF, 128K)

Greenhalgh 2020 (PDF, 165K)

Appendix 7. Excluded studies

Full details are available on request.

Copyright © NICE 2020.
Bookshelf ID: NBK567264PMID: 33555764


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