Priority setting of future research into long-term symptoms of Covid-19 infection (post-acute sequelae of Covid-19 or Long Covid)
Based on the James Lind Alliance method
Prioritisation of scientific evidence gaps
Scientific evidence gaps which most urgently need to be addressed are identified using a method developed by the James Lind Alliance in Great Britain that actively engages a broad range of stakeholders, including health care and social service providers as well as service users and their families.
The full report is available in English as a pdf file using the Download report option.
What research topics matter most to people who have suffer post-acute sequelae of Covid-19 (Long Covid), relatives, clinicians and researchers within the field? The Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) has made an inventory of research topics and invited relevant stakeholders to prioritize, these topics. In the project, long-term symptoms are defined as follows: the condition ”Long-term symptoms of Covid-19” refers to all forms of long-term disease, symptoms, complications and persistent discomfort, associated with Covid-19.”
The aim of the report is to help ensure that questions which are considered particularly urgent will be addressed by well-conducted and relevant research. This can apply both to research in the form of individual new studies, so-called primary research, and in the form of systematic reviews, in which the results of all studies within a specific field are critically appraised and summarized. The main target groups for the report are researchers, the bodies which fund research and authorities and organisations which compile research findings, international and Swedish.
In 2020, SBU was commissioned by the Swedish Government to evaluate the scientific evidence of care for patients with long-term symptoms or sequelae (Long Covid) of the disease Covid-19. The report was published on December 1st, 2020. One of the directives of the commission was to summarize not only published studies but also currently ongoing studies. As Covid-19 is such a novel disease and research to date has focused primarily on treatment of the acute phase of the infection, there are many aspects of long-term symptoms of the disease which require further research. SBU therefore decided to investigate which questions were considered most urgent by patients suffering long-term symptoms of Covid-19, relatives and clinicians and researchers, hence the initiation of this project. As it is unlikely that all research questions will be answered, there is always, conscious or unconscious, a process of prioritising in selecting research topics. This prioritising is usually done from the point of view of researchers, research funding agents (which may include a community perspective) and commercial interests, but seldom from the perspectives of the patients, relatives and clinicians, as to what they consider to be important. In this report we have asked what all these groups jointly consider should be prioritised.
The priority setting process is based on a method developed by the James Lind Alliance. Patients, their relatives or closely connected, clinicians, and other relevant stakeholders are invited to nominate the research questions which they consider, from their perspective, to be important. In the current project researchers were also included even though this is not commonly the case. Clinicians in the current project refers to different professional groups who may be involved with these patients through their work, such as medical doctors, registered nurses, occupational therapists, physiotherapists, psychologists, enrolled nurses and dieticians. The method has an inclusive perspective, with equitable inclusion of the participants, whereby a mutual result is achieved on consensus principles. The method is not intended to produce an absolute truth, but the aim is to broaden the research perspective.
During the project, proposed research questions were collected by means of a questionnaire on SBU’s website.
The priority setting was then undertaken by a working group, starting with two web-based questionnaires, followed by six final priority setting meetings, conducted digitally. The working group participants were recruited through an open interest notification on SBU’s website.
In response to the inventory questionnaire, 1,483 research questions were suggested in total, from 508 individuals. After exclusion of questions which were beyond the scope of the enquiry and combining questions on a similar theme, the result was a list of 97 comprehensive, overarching questions included in priority questionnaire 1.
In all, 553 people notified their interest in participating in the priority setting. Most were people with personal experience of the long-term symptoms of Covid-19. In two successive questionnaires, each participant was requested to select up to ten of the questions which mattered most to them. The results were weighted by perspective, so that all perspectives were included, with those questions they considered should have highest priority carried forward to the next stage.
In total, six separate digital priority setting meetings were held, with 29 participants in all, representing the various perspectives. At each meeting, the participants discussed the remaining 25 questions and came to general agreement as to which questions, they considered were the ten most important. SBU then combined the results of these six meetings to create a final top list (Table 1). All project participants have been given the opportunity to read and comment on the final list.
Several mutual ideas were presented during the six priority setting meetings. This included the proposal that research into why certain people are afflicted with long-term symptoms and the underlying cause to why certain symptoms arise, would provide fundamental knowledge on which treatment studies could be based. Furthermore, participants emphasised research questions which could contribute to improved knowledge, both for those who currently have symptoms and for those at risk (preventive measures). A more detailed description of the reasoning and motivation underlying this prioritising is to be found in Chapter 4 of the report.
The order of questions in the top list does not necessarily reflect the order in which the research should be carried out: it is merely listed in the order of what questions which was considered most important to answer. As several of the questions are broad, several studies may be required to answer them.
Top 10 list of prioritised research questions
|Top 10 list of prioritised research questions about long-term symptoms of Covid-19 (1 = highest ranking).|
|1||What treatment is effective against persistent neurological symptoms and cognitive disturbances (such as brain fog, memory loss, difficulty concentrating, fatigue, numbness, tremor, headache) associated with Covid-19?
How can rehabilitation efforts after long-term symptoms of Covid-19 be optimised and what measures should be included (occupational therapy, physiotherapy, psychology, social worker, speech therapist, dietitian etc.)?
|3||What is the most effective treatment for long-term impaired breathing function/ oxygen uptake or problems with respiratory arrest, associated with Covid-19?|
|4||Why do certain people develop long-term symptoms of Covid-19?|
|5||How can an objective diagnosis be made of people with long-term symptoms of covid-19, regardless of whether they have had a positive PCR test during the acute phase, or if they have demonstrable antibodies?|
|6||Can expanded diagnosis, to investigate which organs are involved, result in better treatment and eventually prevent future complications in people with long-term symptoms of Covid-19?|
|7||What is the underlying cause of the various patterns of symptoms in people with long-term symptoms of covid-19?|
|8||What treatment can be given during the acute phase to prevent the development of long-term symptoms of Covid-19?
What clinical manifestations occur in persons affected by long-term symptoms of Covid-19?
|10||Is the immune response (e.g. T-cell response, antibodies to Covid-19, development of autoimmunity) different in people with long-term symptoms of Covid-19?|
In this project, priority setting of research questions is based on consensus principles, whereby the participants, through questionnaires and meetings, reach mutual agreement on the results. The strength of the method is the inclusive perspective whereby patients, relatives, clinicians, and researchers are equal participants. A prerequisite for the method is that the knowledge and experience of each participant is acknowledged and regarded as having equal value.
Researchers do not usually participate in this type of project: there may be some conflict of interest, whereby they prioritise their own research. In this project however, we decided to include researchers under the same conditions as the other participants. This was partly because Covid-19 is a novel disease and many of the researchers within the field are also clinicians treating Covid-19 patients. To date they have most experience of the issues affecting people with long-term symptoms of Covid-19.
The priority setting covers a broad field and includes everything from basic research, to correlation studies, organisational issues as well as treatment studies. The SBU report on which the work is based, was however limited to investigation of symptoms, treatment and rehabilitation of long-term symptoms of Covid-19. However, as this field of research is so active, collations of research becomes outdated very fast. It is therefore important that researchers document the collected knowledge in this field before they embark on further research, including these questions of high priority. It is also important that in future, the published studies are collated and evaluated in systematic reviews.
The report was reviewed by SBU’s internal quality assurance group, SBU´s scientific advisory board and external reviewers.
- Judith Bruchfeld, Senior medical officer, Karolinska University Hospital
- Emma Mårtensson, patient advocate
- Marie Österberg, Project Manager
- Christel Hellberg, Project Manager
- Irini Åberg, Project Administrator
- Sofia Tranæus, Head of department
How to cite this report
SBU. Priority setting of future research into long-term symptoms of Covid-19 infection (post-acute sequelae of Covid-19 or Long Covid). Stockholm: Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU); 2021. SBU-report 324E.