Category: Overlapping Illnesses

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)

ESCMID rapid guidelines for assessment and management of long COVID

Abstract:

Scope: The aim of these guidelines is to provide evidence-based recommendations for assessment and management of individuals with persistent symptoms after acute COVID-19 infection, and provide a definition for this entity, termed “long COVID”.

Methods: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design.

Recommendations: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high quality prospective clinical studies/trials, including a control group, to further evaluate assessment and management of individuals with persistent symptoms of COVID-19.

Source: Yelin D, Moschopoulos CD, Margalit I, Gkrania-Klotsas E, Landi F, Stahl JP, Yahav D. ESCMID rapid guidelines for assessment and management of long COVID. Clin Microbiol Infect. 2022 Feb 16:S1198-743X(22)00092-1. doi: 10.1016/j.cmi.2022.02.018. Epub ahead of print. PMID: 35182760; PMCID: PMC8849856. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849856/ (Full text)

Neurological manifestations of long-COVID syndrome: a narrative review

Abstract:

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 4: Heart Rate Monitoring to Manage Postexertional Symptom Exacerbation

The physiology underlying postexertional symptom exacerbation (PESE) is abnormal in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and likely long COVID. Activity pacing approaches appear warranted to accommodate the unusual physiological deficits of PESE.

The Rationale for Heart Rate Monitoring

Similar to people living with ME/CFS,7 people living with long COVID have reported finding activity pacing to be helpful. This idea is reflected in current safe rehabilitation guidelines for this condition.8 PESE is challenging to self-manage because of the variability in onset, duration, and nature from person to person.2,6 Social stigma associated with PESE may lead people to overexert to meet the demands of their daily tasks. This stigma may be exacerbated by people telling patients that “it’s all in their head” or they “just need to exercise.” Variability and stigma, in turn, make it difficult to identify important activity triggers in the early stages of learning to manage PESE.

PESE is characterized by aerobic system dysfunction. Pacing based on heart rate can help the patient avoid the dysfunctional aerobic system by keeping their activity intensity at a level anaerobic metabolism will dominate. Heart rate monitoring (HRM) provides an element of predictive potential for the patient to understand when their activities exceed physiological limits and eventually may result in PESE. In this post, we will discuss activity pacing to manage PESE that is based on HRM.

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 4: Heart Rate Monitoring to Manage Postexertional Symptom Exacerbation. Published online on February 23, 2022. https://doi.org/10.2519/jospt.blog.20220223 (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)

Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID Part 2: Physiological Characteristics During Acute Exercise Are Abnormal in People With Postexertional Symptom Exacerbation

In a previous post on the JOSPT Blog, we outlined the connection between postacute sequalae to novel coronavirus (long COVID) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through their common clinical presentation: postexertional symptom exacerbation (PESE). PESE suggests the presence of abnormal physiological responses to exercise/activity. These physiological responses may be measured using cardiopulmonary exercise testing (CPET), which allows for careful characterization of cardiac, pulmonary, and metabolic functioning during exercise. We will review the characteristic findings on CPET in people with PESE.

The Physiology of PESE

One well-established protocol involves consecutive-day CPETs.8 In deconditioned people and people with a whole host of health conditions, CPET measurements demonstrate low error variance. Yet, CPET measurements are known to vary between tests in people with PESE.2 The observed variation in people with PESE reflects the biological variance associated with PESE.2 Clues about biological variance can provide important information about the underlying pathoetiology, severity, and functional limitations present.2,8 CPET data from peak exertion and ventilatory anaerobic threshold (VAT) provide important snapshots of physiological functioning. Data from peak exertion tells us about the physiology of a person’s “top-end” performance, and data from VAT elucidates the physiology of more “everyday” levels of exertion.

Read the rest of this 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 2: Physiological Characteristics During Acute Exercise Are Abnormal in People With Postexertional Symptom Exacerbation. JOSPT blog, Published online on February 9, 2022. https://doi.org/10.2519/jospt.blog.20220209 (Full text)

Is It Useful to Question the Recovery Behaviour of Patients with ME/CFS or Long COVID?

Abstract:

For the last few decades, medical guidelines have recommended treating patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with graded exercise therapy (GET) and cognitive behavioural therapy (CBT). Moreover, doctors have questioned the recovery behaviour of these patients and stimulated them to follow these treatments so that they would be able to go back to work. In this article, we reviewed trials of GET and CBT for ME/CFS that reported on work status before and after treatment to answer the question of whether doctors should continue to question the recovery behaviour of patients with ME/CFS.

Our review shows that more patients are unable to work after treatment than before treatment with CBT and GET. It also highlights the fact that both treatments are unsafe for patients with ME/CFS. Therefore, questioning the recovery behaviour of patients with ME/CFS is pointless. This confirms the conclusion from the British National Institute for Health and Care Excellence (NICE), which has recently published its updated ME/CFS guideline and concluded that CBT and GET are not effective and do not lead to recovery.

Studies on CBT and GET for long COVID have not yet been published. However, this review offers no support for their use in improving the recovery of patients with an ME/CFS-like illness after infection with COVID-19, nor does it lend any support to the practice of questioning the recovery behaviour of these patients.

Source: Vink M, Vink-Niese F. Is It Useful to Question the Recovery Behaviour of Patients with ME/CFS or Long COVID? Healthcare (Basel). 2022 Feb 18;10(2):392. doi: 10.3390/healthcare10020392. PMID: 35207003. https://www.mdpi.com/2227-9032/10/2/392 (Full text)

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Abstract:

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope.

Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

Source: Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537-559. doi: 10.1042/BCJ20220016. PMID: 35195253. https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in (Full text)

Post-corona fatigue-a familiar picture in a new guise?

Abstract:

Background: Myalgic encephalitis or chronic fatigue syndrome (ME/CFS) has again come into focus as a result of coronavirus disease 2019 (COVID-19). Fundamentally problematic is the fact that ME/CFS is considered a separate entity; however, extreme fatigue is also a common symptom of an underlying disease. Our article aims to increase the acceptance of ME/CFS and extreme fatigue facing a symptomatology that is not fully understood, and to highlight the need for research, orientation for physicians, and counselling services for patients.

Materials and methods: Orientative research by focused information gathering.

Results: In various research projects, the hypothesis of post-infectious ME/CFS as an autoimmune disease could be confirmed. In general, the heterogeneity of diagnostic criteria as well as the variety of formulations to describe the symptomatology and different coding options make it difficult to clearly assign symptoms to a clinical picture. Exertion intolerance has been identified as a severe symptom of post-COVID-19 disorder. For this reason, recommendations in international guidelines are currently being revised, especially with regard to pacing. The implications for recommendations in tumor-related fatigue or due to multiple sclerosis are unclear.

Conclusion: Against the background of a decreasing burden of disease due to increasing vaccination rates, research on fatigue should not only include viral diseases.

Source: Buchberger B, Zwierlein R, Rohde V. Post-Corona-Fatigue – das bekannte Bild in neuem Gewand? [Post-corona fatigue-a familiar picture in a new guise?]. Onkologe (Berl). 2022 Feb 17:1-6. German. doi: 10.1007/s00761-022-01102-1. Epub ahead of print. PMID: 35194336; PMCID: PMC8853121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853121/ (Article in German) (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)