Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic

Abstract:

The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions.

The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.

Source: Clark IA. Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic. Pharmacol Res Perspect. 2022 Apr;10(2):e00926. doi: 10.1002/prp2.926. PMID: 35174650; PMCID: PMC8850677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850677/ (Full text)

Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study

Abstract:

Background: There are no outcome studies for coronavirus disease 2019 (COVID-19) survivors one year after hospital discharge in Germany.

Methods: This retrospective cohort study included all patients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalized in the departments of internal medicine of the Klinikum Saarbrücken, a tertiary care hospital, between March 15 and December 31, 2020. A telephone interview with survivors was conducted at least 12 months after discharge. The interview was initiated with an open-ended question whether the patient had fully recovered from the disease. In the event of a subjective incomplete recovery, the patient was prompted to report any continuous or frequent symptoms that had not occurred prior to COVID-19. Finally, independent of the open-ended question response, all patients were asked closed questions which addressed new symptom onset of persistent fatigue, cognitive dysfunction, headache, muscle and joint pain following COVID-19.

Results: In all, 235 survivors were contacted and 162 could be included in the analysis. In 55 of 162 interviews (34.0%) at least one persistent COVID-19 symptom (PCS) was spontaneously reported. Four of 55 survivors with PCS reported five additional symptoms on the closed questions. One survivor, who responded positively to the open-ended question, reported new onset PCS in response to the closed questions. Physical fatigue (24.7%), cognitive dysfunction (14.8%), shortness of breath (8.6%), muscle and joint pain (6.8%) and headache (6.2%) were the most frequently reported PCS.

Conclusions: Despite an interview technique aimed to reduce attribution bias by patients, one third of COVID-19 inpatient survivors report PCS one year after hospitalization.

The complete article is written in English.

Source: Zuschlag D, Grandt D, Custodis F, Braun C, Häuser W. Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study. Schmerz. 2022 Feb 25:1–9. doi: 10.1007/s00482-022-00626-0. Epub ahead of print. PMID: 35217881; PMCID: PMC8877740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877740/ (Full study)

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection

Abstract:

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection.

One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain.

In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.

Source: Bileviciute-Ljungar I, Norrefalk JR, Borg K. Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection. J Clin Med. 2022 Jan 31;11(3):771. doi: 10.3390/jcm11030771. PMID: 35160223; PMCID: PMC8836662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836662/ (Full text)

Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus

Abstract:

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias.

Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease.

In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.

Source: Raman B, Bluemke DA, Lüscher TF, Neubauer S. Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus. Eur Heart J. 2022 Feb 18:ehac031. doi: 10.1093/eurheartj/ehac031. Epub ahead of print. PMID: 35176758. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac031/6529562 (Full text)

‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19

Abstract:

Objective: To explore the lived experience of ‘brain fog’-the wide variety of neurocognitive symptoms that can follow COVID-19.

Design and setting: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.

Method: 50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others’ accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.

Results: Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term ‘brain fog’; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants’ search for physical mechanisms to explain their symptoms.

Conclusion: These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.

Source: Callan C, Ladds E, Husain L, Pattinson K, Greenhalgh T. ‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19. BMJ Open. 2022 Feb 11;12(2):e056366. doi: 10.1136/bmjopen-2021-056366. PMID: 35149572; PMCID: PMC8844964. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844964/ (Full text)

Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study

Abstract:

Objective: To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection.

Design: Retrospective cohort study.

Setting: UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results.

Participants: Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490).

Main outcome measures: The presence of persistent and new sequelae at 21 or more days after a diagnosis of covid-19 was determined with ICD-10 (international classification of diseases, 10th revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was analyzed by age, race, sex, and whether patients were admitted to hospital for covid-19.

Results: Among individuals who were diagnosed with SARS-CoV-2, 32% (27 698 of 87 337) sought medical attention in the post-acute period for one or more new or persistent clinical sequelae, which was 11% higher than the 2020 comparison group. Respiratory failure (risk difference 7.55, 95% confidence interval 7.18 to 8.01), fatigue (5.66, 5.03 to 6.27), hypertension (4.43, 2.27 to 6.37), memory difficulties (2.63, 2.23 to 3.13), kidney injury (2.59, 2.03 to 3.12), mental health diagnoses (2.50, 2.04 to 3.04), hypercoagulability 1.47 (1.2 to 1.73), and cardiac rhythm disorders (2.19, 1.76 to 2.57) had the greatest risk differences compared with the 2020 comparison group, with similar findings to the 2019 comparison group. Compared with the group with viral lower respiratory tract illness, however, only respiratory failure, dementia, and post-viral fatigue had increased risk differences of 2.39 (95% confidence interval 1.79 to 2.94), 0.71 (0.3 to 1.08), and 0.18 (0.11 to 0.26) per 100 patients, respectively. Individuals with severe covid-19 disease requiring admission to hospital had a markedly increased risk for most but not all clinical sequelae.

Conclusions: The results confirm an excess risk for persistent and new sequelae in adults aged ≥65 years after acute infection with SARS-CoV-2. Other than respiratory failure, dementia, and post-viral fatigue, the sequelae resembled those of viral lower respiratory tract illness in older adults. These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus.

Source: Cohen K, Ren S, Heath K, Dasmariñas MC, Jubilo KG, Guo Y, Lipsitch M, Daugherty SE. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ. 2022 Feb 9;376:e068414. doi: 10.1136/bmj-2021-068414. PMID: 35140117; PMCID: PMC8828141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828141/ (Full text)

Neurological manifestations of long-COVID syndrome: a narrative review

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data.

The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae.

In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.

Source: Stefanou M-I, Palaiodimou L, Bakola E, et al. Neurological manifestations of long-COVID syndrome: a narrative review. Therapeutic Advances in Chronic Disease. January 2022. doi:10.1177/20406223221076890 https://journals.sagepub.com/doi/full/10.1177/20406223221076890 (Full text)

Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID Part 3: “Energy System First Aid” for People With Postexertional Symptom Exacerbation

In a previous post, we demonstrated that the symptoms and physiology of postexertional symptom exacerbation (PESE) are inconsistent with deconditioning. PESE worsens in response to exercise and demonstrates a variable clinical presentation. We will build a clinical rationale for energy system first aid as a place to start helping people with PESE.

Graded Exercise May Be Harmful to People With PESE

It is not surprising that patients with PESE frequently report worsening symptoms and function with exercise prescribed based on time and activity quotas,1 based on the physiological evidence. The United Kingdom’s Pacing, graded Activity, and Cognitive behaviour therapy, a randomized Evaluation (UK PACE) compared the clinical outcomes of specialist medical care, adaptive pacing, and graded exercise therapy (GET) in 641 people with idiopathic, disabling fatigue.9 In this study, GET was a quota-based progressive exercise program, where subjects incrementally increased exercise regardless of symptoms. PESE was not a specific recruitment criterion for this trial.8,9 The trial did not adhere to the published protocol, without appropriate justification. The raw data was independently reanalyzed according to the original protocol,10 Upon reanalysis, most symptomatic and functional outcome findings from the UK PACE trial did not reach thresholds for clinical relevance. Many ME/CFS experts contend the results of GET are marginal, probably not clinically relevant or beneficial.10

Despite the important concerns of the UK PACE trial, the trial continues to exert outsized influence on clinical guidelines.3 Some countries’ systems developed formal treatment pathways based on flawed results. Treatment pathways involving GET may have exposed an untold number of patients with ME/CFS worldwide to a GET program that, at best, is marginally effective, and at worst, may be harmful. Recent clinical guidelines for people with PESE, such as long COVID, no longer involve GET.6,7 These omissions reflect the ongoing re-evaluation of how clinical care should proceed for people with PESE, including people with long COVID. Implicit to this re-evaluation is a further reflection on the generally accepted idea that “movement is medicine” in a way that universally benefits clinical populations.

Read the full article HERE.

Source: Todd E. Davenport, Staci R. Stevens, Jared Stevens, Christopher R. Snell, J. Mark Van Ness. Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID Part 3: “Energy System First Aid” for People With Postexertional Symptom Exacerbation. JOSPT blog, Published online on February 16, 2022. https://doi.org/10.2519/jospt.blog.20220216 (Full text)

Long COVID-19 symptoms: clinical characteristics

Abstract:

Background: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate.

Methods: Observational study enrolling outpatients (≥18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement).

Results: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with >2 persistent symptoms was 27% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]).

Conclusion: We observed a slow but high recovery rate at 6 months among these outpatients.

Source: Seang S, Itani O, Monsel G, Abdi B, Marcelin AG, Valantin MA, Palich R, Fayçal A, Pourcher V, Katlama C, Tubiana R. Long COVID-19 symptoms: clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up. Infect Dis Now. 2022 Feb 11:S2666-9919(22)00038-0. doi: 10.1016/j.idnow.2022.02.005. Epub ahead of print. PMID: 35158095; PMCID: PMC8832844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832844/ (Full text)

Assessment and Management of Long COVID

Abstract:

Almost two years into the pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19, the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Broad variability during acute COVID-19 infection is seen, ranging from asymptomatic presentation to death. The vast majority of individuals who develop COVID-19 return to their pre-COVID-19 baseline within several weeks.

However, a portion of patients will develop a post-COVID-19 syndrome of persistent cognitive, somatic, and behavioral symptoms. This syndrome, designated as post-acute sequelae of SARS-CoV-2 infection, is more commonly known as long COVID. The objectives of this paper are to inform psychologists regarding our current understanding of the underlying pathophysiology of COVID-19, review criteria for range of severity during acute illness, present clinical manifestations of long haul phenomena, and discuss the emerging literature base of evidence-based treatment and management approaches.

Source: Rivas-Vazquez, R.A., Rey, G., Quintana, A. et al. Assessment and Management of Long COVID. J Health Serv Psychol 4821–30 (2022). https://doi.org/10.1007/s42843-022-00055-8  (Full study)