National Academies: New Report Reviews Evidence on Long COVID Diagnosis, Risk, Symptoms, and Functional Impact for Patients 2024

[John Mac]

https://www.nationalacademies.org/n...k-symptoms-and-functional-impact-for-patients

News Release | June 5, 2024

WASHINGTON — A new report from the National Academies of Sciences, Engineering, and Medicine presents conclusions about Long COVID diagnosis, symptoms, and impact on daily function — including that Long COVID can cause more than 200 symptoms, and that a positive COVID-19 test is not necessary to make a Long COVID diagnosis.

Since the onset of the COVID-19 pandemic in 2020, many individuals infected with the virus have continued to experience lingering symptoms for months or even years following acute infection. In a 2022 survey, 3.4 percent of U.S. adults and 1.3 percent children reported they were experiencing Long COVID symptoms at the time of the survey.

The new report says that some health effects of Long COVID, including chronic fatigue and post-exertional malaise, cognitive impairment (sometimes referred to as “brain fog”), and autonomic dysfunction, can impair an individual’s ability to work or attend school for six months to two years or more after COVID-19 infection. It can be difficult to clinically assess these health effects, or to determine their severity and effect on a person’s ability to function. They also may not be captured in the Social Security Administration’s Listing of Impairments, which is used as an initial screening step in determining disability.

Even patients with a mild case of COVID-19 can go on to develop Long COVID with severe health effects. Risk factors for poor functional outcomes from Long COVID include being female, lack of or inadequate vaccination against COVID-19, preexisting disability or comorbidities, and smoking. A greater number of or more severe Long COVID symptoms are correlated with decreased quality of life, physical functioning, and ability to work or perform in school.

“Diagnosing, measuring, and treating Long COVID is complicated. This disease, which has existed in humans for less than five years, can present differently from person to person and can either resolve within weeks or persist for months or years,” said Paul Volberding, professor emeritus in the department of medicine at the University of California, San Francisco, and chair of the committee that wrote the report. “Our report seeks to offer a clear summary of what research has found so far about diagnosing Long COVID, and what the disease can mean for an individual’s ability to function in their daily lives.”

“This report offers a comprehensive review of the evidence base for how Long COVID may impact a patient’s ability to engage in normal activities, such as going to work, attending school, or taking care of their families,” said Victor J. Dzau, president of the National Academy of Medicine. “Its findings will be useful to anyone attempting to understand how Long COVID may affect the millions of people in the U.S. who have reported symptoms.”

 

[Dakota15]

NASEM press release: 'New Report Reviews Evidence on Long COVID Diagnosis, Risk, Symptoms, and Functional Impact for Patients'

'Undertaken by the Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration, the study was sponsored by Social Security Administration.'

 

[Dakota15]

LA Times by Emily Alpert Reyes: 'Positive test not needed for long COVID diagnosis, experts conclude'

'People do not need to have tested positive for the coronavirus to be considered for a diagnosis of long COVID, a new report from NASEM concludes’

'Demand for specialty care to help long COVID patients has outstripped capacity, resulting in waiting lists. Meanwhile, patients can encounter skepticism about their symptoms, which discourages them from seeking care and can particularly affect those who are disadvantaged..’

'Long COVID shares many features with other chronic conditions, such as myalgic encephalomyelitis, also known as chronic fatigue syndrome; fibromyalgia; and postural orthostatic tachycardia syndrome, or POTS. More research is needed on how to manage such illnesses.’

Volberding said many other questions about long COVID are yet to be settled.

“This is an area where society — and Social Security — are going to need to keep their eye on this as we continue to learn more.’

“These people with long COVID really are suffering,” he added. “Even if we’d rather, as a society, ignore the pandemic altogether, you can’t ignore the challenge that these people are facing.”

 

[Wyva]

It is quite long of course, so I haven't read it all but there is an entire chapter titled "Chronic Conditions Similar to Long Covid"

It points out very well how long covid or at least a percentage of LC is eerily similar to ME/CFS, gives a lot of info about ME/CFS and in general I thought it was quite alright. (ME/CFS is not the only condition mentioned though, fibromyalgia, POTS, hEDS and post-treatment Lyme syndrome are discussed as well, with varying emphasis. ME/CFS gets a lot of attention though.)

And then I saw the sections titled "Multidisciplinary Care and Rehabilitation" on page 196 of the same chapter and "Psychosocial Support" on the next page and I wasn't so impressed. These go way to easy on physical rehab and CBT. There is a warning about GET but also recommendation of physical rehab and basically the section says GET "requires caution" in the treatment of ME/CFS because of the potential harm. Nothing about the fact that neither GET or CBT are actually supported by evidence. It gives the impression that GET is OK in treating ME/CFS as long as you are careful.

 

[Dakota15]

CIDRAP: “Report: More than 200 symptoms tied to long COVID”

“The findings are meant to guide the Social Security Administration (SSA) and are published one week before NASEM is set to offer a new single definition of long COVID…”

“Emphasized throughout the report is the similarity long COVID has to other chronic conditions, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, and postural orthostatic tachycardia syndrome (POTS).“

“Like those conditions there is no current way to treat long COVID, though long COVID does have a better prognosis than does ME/CFS.”

 

[rvallee]

At least it adds to the weight of why this needs to be researched, but frankly the part about rehabilitation more than anything emphasizes how rehabilitation medicine is a mess where evidence barely matters and outcomes even less so, to the point where it should be entirely ignored most of the time.

One of the highlights is:

There is no curative treatment for Long COVID. Management of the condition is based on current knowledge about treating its symptoms and health effects. As with other complex chronic health conditions, medical treatment for Long COVID is focused on managing symptoms and optimizing quality of life and function.

And current knowledge is essentially nil, while rehabilitation has never shown any positive impact, but it's recommended anyway. In a discipline marred with low-quality knowledge, rehabilitation evidence-based medicine is really as low as it gets.

 

[rvallee]

A summary on "similar chronic conditions":

Long COVID shares many features with other complex multisystem conditions, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, and postural orthostatic tachycardia syndrome (POTS). The mechanism of action for infection-associated chronic illnesses remains unclear, and further investigation is needed. Current theories regarding potential mechanisms of action include viral persistence, immune dysregulation (including cytokine dysregulation or mast cell activation), neurological disturbances (e.g., neuroinflammation), cardiovascular damage (e.g., endothelial dysfunction, coagulation issues, orthostatic intolerance), gastrointestinal dysfunction (e.g., secondary to gut microbiome dysbiosis), metabolic issues (energy insufficiency, reactive oxygen species production, mitochrondrial dysfunction), and genetic variations.

Currently, there are no specific laboratory-based diagnostic tests for Long COVID or ME/CFS, and diagnosis involves consideration of other potential causes of the symptoms. In general, Long COVID (especially that which does not meet criteria for ME/CFS) has a better prognosis than ME/ CFS. Some manifestations of Long COVID are similar to those of ME/CFS, and like ME/CFS, Long COVID appears to be a chronic illness, with few patients achieving full remission. Studies comparing Long COVID and ME/ CFS have several limitations, however. Because Long COVID is a new disease, study participants are usually newly diagnosed, while ME/CFS study participants often have had the condition for longer and so are less likely to improve. Moreover, the definition of ME/CFS requires that symptoms be ongoing for 6 months or more, whereas the duration criteria for Long COVID vary in the literature from 2 to 6 months, making the two conditions difficult to compare.

Based on its review of the literature, the committee reached the following conclusion:

9. Complex, infection-associated chronic conditions affecting multiple body systems are not new, and Long COVID shares many features with such conditions as myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural orthostatic tachycardia syndrome. Current theories about the pathophysiology of these conditions include immune dysregulation, neurological disturbances, cardiovascular damage, gastrointestinal dysfunction, metabolic issues, and mitochondrial dysfunction. More research is needed to understand the natural history and management of complex multisystem chronic conditions, including Long COVID.​

​

 

[Yann04]

I find it so weird how people who meet ME diagnostic criteria after a covid infection are said to have long covid and not ME/CFS? Shouldn’t they be counted to have both?

 

[rvallee]

PEM is widely discussed throughout, and very prominently. In a sane world with a medical profession that is accountable and self-critical, the dismissal of PEM for decades, including from the prominent voices who have pushed the psychosomatic model, should be a massive embarrassment. If only facts mattered.

PEM, also called post-exertional symptom exacerbation, is characterized by a severe worsening of fatigue and other symptoms following physical, mental, social, or emotional exertion that would not typically cause such a reaction in healthy individuals. This exacerbation of symptoms can occur immediately after the stressor or can be somewhat delayed (hours to days). In addition, an episode of PEM can last for days or even weeks. The specific symptoms that worsen vary among individuals, but often can go beyond fatigue to include muscle or joint pain, cognitive difficulties, sleep disturbances, headaches, flu-like symptoms, and/or gastrointestinal disturbances (Vernon et al., 2023).

Fatigue, broadly defined as a distressing or persistent tiredness that is neither proportional to recent activity nor alleviated by rest (Sandler et al., 2021; Twomey et al., 2022), is the most dominant symptom of Long COVID in several studies, ranging from 19 percent to 76.3 percent of patients (Cheung et al., 2023; Hartung et al., 2022; Ho et al., 2023; Kayaaslan et al., 2021; Líška et al., 2022; Sánchez-García et al., 2023; Štepánek et al., 2023). Of the many descriptive studies that have captured fatigue and other symptoms seen in Long COVID, only a small proportion make it a point of measuring PEM. In a large cross-sectional sample of adults who were selected from post–COVID-19 online groups, PEM was reported by 89.1 percent (95% confidence interval [CI] 88–90%); for most participants, PEM lasted a few days (Davis et al., 2021). A recent analysis of the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) longitudinal study was aimed at developing and validating a quantitative definition of Long COVID using multiple symptoms. In that study, PEM was reported in 87 percent of patients identified as having Long COVID (Thaweethai et al., 2023).

Both post-COVID fatigue and PEM are generally diagnosed based on patient-reported symptoms and a detailed medical history. Typically, a thorough medical evaluation, which may include blood tests, imaging studies, and other diagnostic tests, is conducted to rule out other possible causes or contributing factors.

In clinical settings, health care providers typically evaluate chronic fatigue and PEM by asking patients to describe their symptoms in detail, including by inquiring about the type of exertion (physical, emotional, or mental) that leads to worsening of symptoms; the duration and severity of the symptom worsening that follows those stressors; how long it takes for the symptoms to return to baseline; what symptoms are experienced; and whether there is a prodrome related to the worsening of the symptoms. Multiple validated questionnaires can be used to measure a person’s perception and severity of fatigue and PEM (Davenport et al., 2023; FACIT, 2021), such as the DePaul Symptom Questionnaire–Post-Exertional Malaise (DSQ-PEM), which captures the frequency and severity of PEM symptoms (Bedree et al., 2019; Cotler et al., 2018; Davenport et al., 2023; FACIT, 2021).

One approach to diagnosing PEM, investigated in myalgic encephalitis/ chronic fatigue syndrome (ME/CFS) but not yet in Long COVID, involves two consecutive days of cardiopulmonary exercise testing (CPET) (Stevens et al., 2018). Deconditioned adults and those with other chronic conditions show minimal variation between the first and second day of CPET measurement. In ME/CFS patients with PEM, multiple studies reveal a significant decline in oxygen consumption (V∙ O2) at peak performance and the ventilatory anaerobic threshold on the second day of CPET testing (Davenport et al., 2019; Stevens et al., 2018). The ventilatory anaerobic threshold reflects a person’s ability to sustain continuous work and is more related to everyday exertion. This drop in V∙ O2 between the first- and second-day CPET measurements suggests that patients with PEM risk entering anaerobic metabolism during activities they could have completed without it just the day before (Stevens et al., 2018). In ME/CFS, symptoms most associated with PEM after exercise include cognitive dysfunction, reduced self-reported daily functioning, and mood disturbances (Chu et al., 2018). Although 2-day CPET helps with understanding the physiologic response to exercise in patients with PEM generally, there are health system and patient-level barriers that potentially limit the broad implementation of 2-day CPET in diagnosing PEM in Long COVID and ME/CFS. The health system barriers include limited or inequitable access to CPET, with even fewer trained clinicians who can apply and interpret 2-day CPET to diagnose PEM. Patient-level barriers include prolonged recovery from testing and the prohibitive cost of testing without adequate insurance coverage. Several studies have explored the role of CPET in Long COVID, but not all have used PEM as an inclusion criterion (Baratto et al., 2021; Durstenfeld et al., 2022; Evers et al., 2022; Wernhart et al., 2023). Although much of the existing research on 2-day CPET in PEM has been in patients with ME/ CFS, the findings should be expected to generalize, regardless of suspected onset. Nevertheless, additional research is needed to compare 2-day CPET results in Long COVID versus ME/CFS.

Chronic fatigue symptoms in Long COVID impact a person’s ability to work and perform activities of daily living, which makes clinical care and rehabilitation a priority for these patients (Walker et al., 2023). They can also impact productivity by preventing a return to pre-COVID functional levels, thereby affecting the social and economic health of the impacted individual. A cross-sectional observational study on the impact of fatigue on function in 3,754 Long COVID patients, conducted at 31 post-COVID clinics in the United Kingdom, found that 94 percent (3,541) were of working age (18–65 years); half (n = 1,321/2,600, 50.8 percent) of those who completed the “working days lost” questionnaire reported the loss of at least 1 day of work in the last month. Approximately 20 percent (20.3 percent) reported losing 20–28 days of work, and 20 percent also reported the inability to work completely. These results were associated mainly with fatigue (Walker et al., 2023). Symptoms of chronic fatigue in Long COVID may also influence a person’s attitudes toward leisure time, thereby impacting mental health functioning and perceived stress.

Since PEM is considered a hallmark symptom for diagnosing ME/CFS (CDC, 2021b; IOM, 2015; NICE, 2021d), Long COVID patients with PEM may also fit criteria for ME/CFS. Understanding the functional impact of PEM is made more challenging by the fluctuating nature of the symptom complex and the fact that often people can compensate for limitations in function by first making compensatory changes in the time, effort, and resources they ascribe to certain tasks or by making compensatory changes in their social or leisure activity patterns (NICE, 2021d).

Honestly, this may as well be a report on ME/CFS.

 

[rvallee]

I find it so weird how people who meet ME diagnostic criteria after a covid infection are said to have long covid and not ME/CFS? Shouldn’t they be counted to have both?

They discuss this, page 66:

Since PEM is considered a hallmark symptom for diagnosing ME/CFS (CDC, 2021b; IOM, 2015; NICE, 2021d), Long COVID patients with PEM may also fit criteria for ME/CFS.

But still go on elsewhere about rehabilitation being important, as long as it ignores PEM. Which still fundamentally misunderstands PEM.

 

[rvallee]

There is still so much of the old disinformation, though. So much about exercise, all based on the old misinterpretation and psychosomatic models. This part is very disappointing, so much debunked junk that is kept around even though the entire basis for their claims is completely destroyed overall by the report.

 

[rvallee]

Psychosomatic: 0 hits.
Biopsychosocial: 0 hits.
Wessely: found twice, old studies of little importance.
PACE not mentioned. White absent, too.
A few mentions of the 2021 NICE guidelines.

Few mentions of CBT, all here except for 2 citations:

Chronic conditions pose a significant burden with respect to psychological health. Protocols for cognitive-behavioral therapy (CBT) or mindfulness are not standardized for the treatment of Long COVID, ME/CFS, or FM (Friedberg, 2016; O’Dowd et al., 2006; Worm-Smeitink et al., 2016). CBT and mindfulness are the most widely studied psychological interventions for managing pain. Changes in different brain regions observed after CBT include grey matter volume, activation/deactivation, and intrinsic connectivity. CBT involves cognitive and emotional regulation, with the dorsolateral prefrontal cortex, orbitofrontal cortex, right ventrolateral prefrontal cortex, posterior cingulate cortex, and amygdala being key regions. After CBT, the brain shows stronger top-down pain control, cognitive reassessment, and altered perception of stimulus signals (Arroyo-Fernández et al., 2022). Research is currently ongoing on the effectiveness of CBT (NCT05676047, NCT05597722, NCT05731570) or forms of cognitive rehabilitation in Long COVID, including behavioral amygdala-insula retraining (NCT05851846), sound mindfulness strategies (NCT05848401), mind–body reprocessing therapy (NCT05703074 & NCT05422924), behavioral and coping coaching (NCT05752331 & NCT05453201), and mindfulness (NCT05566379 & NCT05422924).

Way too many references to exercise, while discussion of GET is limited to this:

Patients with neuromuscular weakness can benefit from physical rehabilitation. It has been hypothesized that standardized exercise testing for cardiorespiratory fitness after recovery from acute COVID-19 can be used to improve the understanding of Long COVID. However, the use of graded exercise therapy (GET) requires caution in the treatment of ME/CFS because of the potential for iatrogenic harm. There is widespread and valid concern that exercise programs, even graded, may result in deterioration of the patient’s condition given the underlying pathology of disease and the potential to trigger post-exertional malaise and exacerbate symptoms following activity (Tuller and Vink, 2023). It is important at this time to highlight the lessons that can be learned from ME/CFS regarding this need for caution in the use of GET (Torjesen, 2020; Tuller and Vink, 2023; Twisk and Maes, 2009).

Fear: 0 hits.
Belief(s): 0 hits.
Catastrophizing:0 hits.
Kinesiophobia: 0 hits.
FND: 0 hits.
Functional disorder: 0 hits.
Somatization: 0 hits.

Bit embarrassing: Sharpe: 0 hits.

Imagine cosplaying, hell being recognized internationally, as an expert on an issue, being a major player in a name and conceptual change, and in a major report from a major academic institution about the single biggest increase in its incidence in history, you are entirely out of the discussion, as is pretty much everything you spent your career on. Even as it remains, to this day, the dominant model. It's both dominant and irrelevant at the same time.

 

[Yann04]

Bit embarrassing: Sharpe: 0 hits.

I’m liking the fact that David Tuller got more citations than sharpe in this review.

 

[Medfeb]

They discuss this, page 66:

But still go on elsewhere about rehabilitation being important, as long as it ignores PEM. Which still fundamentally misunderstands PEM.

Part of this is because their Long COVID definition is broad - "signs, symptoms, and conditions are present 4 weeks or more after the initial phase of infection" and "it's not one condition."

On the other hand, its not clear how deeply they dug into some of the literature (this was not intended as a systematic review). So for instance, in the meeting, they were asked about the purpose of CBT and they said "CBT can be helpful for a variety of reasons. Reasons not discussed in report. It can be used in various ways – coping but also mental health issues and compensatory strategies." So at least for CBT, it was a non-specific recommendation without crisp rationale for specific subpopulations of LC

 

[Medfeb]

I haven't read the report but generally thought the panel members presenting got it. For instance, one acknowledged that doctors might react negatively because these patients are not going to get better quickly and will require a lot of work - which could result in discrimination against patients.

Not sure how this plays out in other countries but in the US, it results in a strong disincentive for doctors because that time and effort is not reimbursed by our medical system.

 

[Wyva]

Part of this is because their Long COVID definition is broad - "signs, symptoms, and conditions are present 4 weeks or more after the initial phase of infection" and "it's not one condition."

But in that section they are not talking about long covid specifically. This whole part, quoted by @rvallee and linked by me earlier in the thread is in the chapter about similar chronic conditions, ME/CFS, fibromyalgia etc.

These are the quotes:

A systematic review of nonpharmacological treatments in post-viral syndromes (including Long COVID) suggested interventions using Pilates exercises, resistance exercise, telerehabilitation, neuromodulation, and music therapy (Chandan et al., 2023).

Patients with neuromuscular weakness can benefit from physical rehabilitation. It has been hypothesized that standardized exercise testing for cardiorespiratory fitness after recovery from acute COVID-19 can be used to improve the understanding of Long COVID. However, the use of graded exercise therapy (GET) requires caution in the treatment of ME/CFS because of the potential for iatrogenic harm. There is widespread and valid concern that exercise programs, even graded, may result in deterioration of the patient’s condition given the underlying pathology of disease and the potential to trigger post-exertional malaise and exacerbate symptoms following activity (Tuller and Vink, 2023). It is important at this time to highlight the lessons that can be learned from ME/CFS regarding this need for caution in the use of GET (Torjesen, 2020; Tuller and Vink, 2023; Twisk and Maes, 2009).

As I said earlier, this sounds like GET can be a valid treatment for ME/CFS as long as it is done cautiously. Whereas there is zero evidence it works as a treatment at all but there is no mention of that. Actually the evidence points to the opposite. Potential harms are acknowledged but this paragraph is still not good.

I was actually thinking about sending this to the Ministy of Inferior / Professional Health Colleges here, whom I currently in correspondence with about a consensus recommendation about ME/CFS. A lot of the text is actually pretty good and useful. But those paragraphs about rehabilitation of ME/CFS and post-viral conditions really gave me a pause and now I'm really on the fence if this is worth sending simply because of that part.

 

[Dolphin]

"Overlap in Common Symptoms on Long Covid, ME/CFS, and #Fibromyalgia "

https://twitter.com/user/status/1798744264429769062

 

[Dolphin]

Table 5.2 Summary of Potential Biological Mechanisms of #LongCovid, #MyalgicEncephalomyelitis/ #ChronicFatigueSyndrome (#MECFS), & #Fibromyalgia (#FM)

https://twitter.com/user/status/1798747249469743272

 

[Yann04]

Out of curiosity why did they include downregulation of HPA-Axis in that chart given they say it is a potential mechanism for none.

 

[rvallee]

I haven't read the report but generally thought the panel members presenting got it. For instance, one acknowledged that doctors might react negatively because these patients are not going to get better quickly and will require a lot of work - which could result in discrimination against patients.

Not sure how this plays out in other countries but in the US, it results in a strong disincentive for doctors because that time and effort is not reimbursed by our medical system.

I've seen a disturbing number of comments lately about this, explicitly about frustration over not improving that made their MD push for exercise rehabilitation and psychosomatic explanations, probably because this is a common biopsychosocial framing. This is a serious problem, and it's great that it's put in writing in such an authoritative report.

Even if that report has such problematic parts about rehabilitation that it could do as much harm as good. There is a huge problem with how medicine relies on low-quality evidence, which no other profession would even consider. It's infected everything.