Nath said that the epidemiology of long COVID is still unclear because the disease is not well defined. Although research is advancing, there are currently no good diagnostic tests for long COVID, and no established, effective treatments. Gaps in the understanding of the pathogenesis also remain, he said. Lacking resources is a persistent issue, but Nath expressed optimism at the range of philanthropic, federal, and nonprofit entities that are contributing funds into relevant research and development activities.

Several presentations from this workshop pointed to the possibility of viral persistence in the body as a driver of chronic illness, Nath stated. Viral persistence may be linked to lingering remnants of defective virus, remaining viral products that have not been cleared, or reactivation of other latent viruses. There has also been sufficient evidence that innate immune activation, autoimmune antibodies, immune exhaustion, and genetic factors may predispose some to developing these chronic conditions.

Nath concluded with a list of potential priority areas for future progress:

• Agreeing on a common term, such as infection-associated chronic illnesses, to serve as an umbrella for uniting research endeavors.
• Prioritizing patient engagement at every step of the research process.
• Developing diagnostics and biomarkers and improved models to study diseases.
• Replicating and scaling multidisciplinary clinics.

diagnostics and treatments are developed. The pace of traditional research is extremely slow, and previous reasons for this slow progress, such as the lack of definitive biomarkers or murky endpoints are no longer acceptable, she stated. Johnson quoted a 2017 article by Tom Frieden, saying,

There will always be an argument for more research and for better data. But waiting for more data is often an implicit decision not to act, or to act on the basis of past practice rather than on the best available evidence. (Frieden, 2017)

It is critical for clinicians to be given clinical discretion to try different interventions that are safe and could help patients who are suffering in the present, she said, noting that patients are willing to try nearly anything. While applying different treatments, it is also necessary to capture those data and learn from them. She called for combining and capturing data wherever they are available, whether from patient registry data, biorepositories, or clinical trial results, and considering everything together in parallel.

Peter Rowe, Johns Hopkins University, followed by stating the need for support of clinical care for those who are desperate to feel better. There is a need for more clinical capacity, he said, but there is also a need for financial support for clinics, as many patients are unable to afford services in the traditional fee-for-service model. Financial support services that have been provided for HIV care or pediatric cancer could serve as a model for making treatment more accessible at clinics that specialize in chronic illnesses. Rowe noted the importance of studying clinical observations in addition to laboratory observations, as much has been learned about conditions such as Ehlers-Danlos syndrome by examining cascading symptoms expressed in patients. Rowe said that while mast cell activation syndrome was not described in detail at this workshop, allergic phenomena are typically overrepresented in patients with ME/CFS. There are some treatments effective for these symptoms, but they should be studied in clinical trials with the antiviral therapeutics to examine drug interactions. He suggested merging the study of clinical observations and laboratory research.

DISCUSSION

A participant asked about the importance of incorporating systems biology and centralizing data into a common platform. Nath noted that systems biology is important for any disease but acknowledged a continuing struggle regarding how to truly share data when massive amounts are being collected, and stated that the research community should be actively pursuing this goal. Proal added that this is central to her group’s collaboration framework, and they are exploring the use of a data integration platform like LabKey. This

allows for multiple sites to participate and store data in a single open access location. She highlighted the Center Grant Mechanism (U54 grants) through NIH, which contain a clinical core and an administrative core that enable open communication, and noted the NIH requirement that data are uploaded into a central data integration platform. She encouraged NIH to continue to offer those types of grants for infection-associated chronic illnesses and added that many researchers are looking for more high-risk/high-reward, faster turnaround funding mechanisms to help them be more responsive to identified problems and needs.

Speakers also highlighted barriers that need to be proactively addressed to advance progress. Nath noted that regulations, laws, and policies can be challenging, but that they are also necessary for ensuring safety. At the clinical level, Rowe said that taking care of people with chronic illnesses has its own challenges. For example, nearly every treatment prescribed for ME/CFS patients is off-label, and then insurance companies require a prior authorization, which creates administrative burden. There are numerous barriers when it comes to insurance, he said, which can significantly slow patient care.

Tim Coetzee, National Multiple Sclerosis Society, said the invisibility that people with infection-associated chronic illness experience has begun to decrease. He noted that much more work remains to be done, but progress is being made. MS was believed to be an infection-associated chronic illness in the 1980s, but that vocabulary and terminology did not exist at the time. There was not much in the way of treatment back then either, but researchers tested the use of interferons as therapeutics with small numbers of patients. This resulted in some positive response that led to a series of trials and then led to the current standard of care, he said. Coetzee provided three lessons for the work that is still needed today:

1. Doctors need to listen to patients and create space for the community that is affected in all stages of research and treatment.
2. “Start where we are with what we have.” Take action with currently available tools and information in order to best care for patients who are suffering.
3. Persistence is key. Collaboration, coordination, and allyship can be exerted to find ways to lower barriers.

Millions of people live with these infection-associated chronic illnesses. They are counting on researchers and clinicians who can take collective action to dramatically change their world, Coetzee concluded. Additional suggestions from speakers throughout the workshop on promising strategies for learning across diseases, potential research, treatment, diagnostic approaches, critical gaps, and next steps are outlined in Box 7-1.

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