Synopsis of 2024 VA Long COVID Clinical Guidance for U.S. Veterans: Part 1, Nervous System–Related Symptoms, 2025, Wander et al

[forestglip]

Synopsis of 2024 VA Long COVID Clinical Guidance for U.S. Veterans: Part 1, Nervous System–Related Symptoms

Wander, Pandora L.; Awan, Omar; Neal, Jacqueline; Seidel, Ilana; Bell, Kelsie A.; Cassell, Andre; Fattal, Deema; Ng, Bernard; Pyne, Morgan L.; Rog, Lauren; Helfand, Mark

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Description
Long COVID is common and includes nervous system–related symptoms (e.g., autonomic dysfunction, cognitive impairment, fatigue, and pain). We sought to develop just-in-time evidence-informed guidance for nervous system–related Long COVID, a condition for which mature evidence is limited.

Methods
The U.S. Veterans Affairs (VA) Veterans Health Administration (VHA) Long COVID Field Advisory Board commissioned an expert panel that worked with a GRADE methodologist to develop an evidence-to-decision framework for emergent conditions by applying core elements of the Standards for Developing Trustworthy Clinical Practice Guidelines and those of GRADE. We also convened a multidisciplinary writing group that identified a list of clinically relevant questions and commissioned an independent review and synthesis of existing evidence.

The writing group conducted structured discussions and used this evidence base to make recommendations for evaluation and treatment (“Evidence-informed Recommendations”). For history-taking, physical exam, and commonly used, noninvasive diagnostic tests, statements were based on consensus determinations of useful and safe care (“Good Practice Statements”).

We used a Whole Health Systems approach to support the development of guidance that was patient-centered, culturally appropriate, and available regardless of literacy or disability. Feedback was solicited from Veterans and other stakeholders. Where the published literature was insufficient, we used evidence from treatment of similar conditions.

Recommendations
We drafted 30 Evidence-informed Recommendations and 41 Good Practice Statements for nervous system–related Long COVID in Veterans and disseminated them VA-wide, targeting specialty care providers. More research on the effectiveness of diagnostic and therapeutic interventions is needed. In particular, evidence “borrowed” from other conditions and populations should be replaced or supplemented by evidence in Long COVID. Clinical guidance should be updated as this evidence becomes available.

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[SNT Gatchaman]

POTS is the major phenotype of autonomic dysfunction among individuals with Long COVID. Many of our recommendations for diagnosis and management of POTS were consonant with evidence-informed guidelines from the Canadian Cardiovascular Society. In some instances, however, our recommendations diverged from those of other groups not based on the evidence but on applicability to VA populations. The CCS POTS position statement recommended that clinicians consider the use of midodrine (strong recommendation) and fludricortisone (weak recommendation) as part of a treatment algorithm. However, given the high prevalence of conditions that may complicate the use of these drugs (such as heart failure and renal disease) in VA, we offered no recommendation for or against their use in our population.

Historically, experts widely believed that exercise intolerance in postural tachycardia was due to deconditioning, a theory that was based on small, flawed, poorly controlled studies of patients referred for evaluation after months or even years of inactivity. This theory has been discredited by more recent evidence implicating other factors, particularly autoimmunity, in dysregulation of the autonomic system leading to POTS. Considering the weak evidence supporting exercise as a primary treatment, we advised that, when post-exertional malaise was not a prominent symptom, clinicians “consider use” of physical activity in individuals with Long COVID autonomic dysfunction or postural tachycardia.

For the MoCA, we identified minimally adequate evidence that we thought was sufficiently applicable to VA populations. The accuracy of the MoCA varied among studies in several cohorts of post-COVID patients. Sleep apnea and depression are common in Veterans. In the presence of these comorbidities, a low MoCA score may reflect reversible symptoms and not true cognitive impairment. Conversely, a patient with a normal MoCA score may still have cognitive impairment. Thus, we recommended that clinicians consider not using the MoCA alone to identify cognitive impairment in Long COVID.

We also found little evidence addressing the value of offering formal neurocognitive testing to all individuals presenting with concern for Long COVID. As we considered a recommendation on neurocognitive testing, we weighed unstudied harms or impacts on utilization if we were to broadly recommend a test that required subspecialty referral. Given a lack of evidence of benefits and concern about impacts on utilization, we chose not to offer a recommendation on the broad use of formal neurocognitive testing for suspected cognitive impairment in Long COVID.

The evidence review found some evidence for modest, mostly positive effects of cognitive rehabilitation on cognition in mild TBI, although evidence was inadequate to inform the choice of specific cognitive rehabilitation interventions. Thus, while aware of the serious limitations in the evidence, we found on balance that cognitive rehabilitation was low risk of harm and made a conditional recommendation to consider use, with caveats for patients in whom post-exertional fatigue is a major symptom (see next section).

Patients with Long COVID fatigue may have findings characteristic of ME/CFS, particularly post-exertional malaise (PEM), a prolonged or delayed worsening of symptoms that occurs after minimal physical or mental activity and may be out of proportion to the amount of activity that has been done. We categorized fatigue with nervous system symptoms due to its frequent co-occurrence with cognitive impairment, its exacerbation by cognitive exertion, and its contribution to PEM. The review found few studies of interventions to improve exercise tolerance or fatigue severity in Long COVID. Thus, the reviewers also examined recent systematic reviews of treatments for ME/CFS by NICE and the Agency for Healthcare Research and Quality (AHRQ), which recommended against the use of any exercise programs that use a fixed increase in incremental activity based on internal findings that suggest graded protocols may be harmful.

Based on the evidence in ME/CFS, for patients with Long COVID who have fatigue and ME/CFS features, we recommended that clinicians consider not using protocols that rely on fixed incremental increases in activity—such as graded exercise therapy (GET)—to improve exercise tolerance and fatigue severity. Instead, clinicians may consider an individualized program of paced activity and energy conservation, with the caveat that evidence regarding the use of these programs in individuals with Long COVID is limited. Energy management (or pacing) is a self-management strategy that involves managing activities so as not to exceed an individualized “energy limit,” below which an increase or worsening of symptoms is not triggered. Once a patient is effectively pacing without triggering PEM, it may be possible to engage in very short periods of activity to increase stamina. This must be individualized around severity and PEM triggers.

The review did not identify studies of cognitive behavioral therapy (CBT) for fatigue in Long COVID. However, the systematic reviewers identified a randomized trial that is expected to be completed near the end of 2024 (NCT05676047), and the writing group identified a completed trial of CBT, ReCOVer, published in December 2023, in self-referred patients who had persistent fatigue 3–12 months after COVID. The latter was referred to the systematic reviewers to determine its eligibility post hoc. It reported modest benefits but had limited applicability to individuals with Long COVID, or Veterans (on one hand, PEM was not considered, and on the other, individuals with post-traumatic stress disorder were ineligible). After considerable debate, the writing group decided that a recommendation to consider use of CBT would be reasonable at this time, with the caveats that CBT requires numerous visits, which can be especially challenging for populations with PEM.

With regard to pharmacologic treatments for fatigue in Long COVID, the review did not identify controlled trials of low-dose naltrexone (LDN) in populations with Long COVID. However, the writing group noted that the feasibility of using LDN in a VA Long COVID clinic has been established and that clinical trials of LDN are under way. For cognitive impairment and pain, no recommendation was offered. On the other hand, the writing group found that minimally adequate, indirect evidence suggests that clinicians might consider use of LDN for fatigue in individuals with Long COVID who also meet the clinical criteria for fibromyalgia and ME/CFS.

 

[SNT Gatchaman]

We recognize that the severity and persistence of symptoms may leave patients so debilitated that they may be willing to pursue treatments even in the absence of robust clinical evidence or strong guideline endorsement. When facing diagnostic uncertainty (or when existing evidence is limited), clinicians should prioritize transparent, patient-centered communication. This involves validating the patient’s experience and openly discussing what is known versus what is based on clinical experience or individual reports. For patients significantly distressed by symptoms, safe interventions with limited evidence can be considered, always with clear acknowledgment of the evidence gap and a commitment to ongoing reassessment. This approach balances scientific rigor with compassionate, individualized care.

 

[Utsikt]

For patients significantly distressed by symptoms, safe interventions with limited evidence can be considered, always with clear acknowledgment of the evidence gap and a commitment to ongoing reassessment. This approach balances scientific rigor with compassionate, individualized care.

«If the patient becomes too annoying for you, consider telling some fairytales at their expense and risk.»

How very responsible of the practitioners..

 

[Amw66]

«If the patient becomes too annoying for you, consider telling some fairytales at their expense and risk.»

How very responsible of the practitioners..

If you can't cope with not being able to help and can't tell it as it is to the patient, here's your fall back