Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

PM&R, Journal Year: 2023, Volume and Issue: 15(5), P. 640 - 662

Published: March 29, 2023

COVID-19 has been a transformative novel disease in modern health care. Unlike many other viral illnesses, not only causes multiorgan damage during the acute stage of infection, but also potential to cause long-term sequelae, as part post-acute sequelae SARS-CoV-2 infection (PASC) or long-COVID syndrome. In 2022 study released by Centers for Disease Control and Prevention,1 electronic record (EHR) data were examined from time period March 2020–November 2021 persons United States aged ≥18 years assess incidence 26 conditions often attributable post-COVID-19. Among all patients, 38% individuals experienced an incident condition compared with 16% controls; affected multiple systems included cardiovascular, pulmonary, hematologic, renal, endocrine, gastrointestinal, musculoskeletal, neurologic, psychiatric signs symptoms.1 Neurological symptoms occur approximately 80% hospitalized patients phase infection.2 The most prevalent PASC neurologic that remain after 3–4 weeks initial include "brain fog" (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), myalgias (55%).3 Importantly, studies outcomes across care-setting spectrum (nonhospitalized, hospitalized, admitted intensive care) continue emerge. Addressing this knowledge gap is important helping guide care strategies system capacity planning. U.S. Department Veterans Affairs national databases used build cohort 154,068 COVID-19, 5,638,795 contemporary controls 5,859,621 historical estimate risks burdens disorders at 12 months following COVID-19. elevated even people who did require hospitalization Investigators found increased risk various including ischemic hemorrhagic stroke, cognition memory disorders, peripheral nervous episodic (eg, migraine seizures), extrapyramidal movement mental musculoskeletal sensory Guillain–Barré syndrome (GBS), encephalitis encephalopathy.4 up 10% critically ill have cranial nerve involvement.6 Sleep patterns can be disturbed these neurological turn, exacerbate symptoms.7-10 Interestingly, presence severity do fully correlate symptoms.11 Another claims involving 78,252 demonstrated 75.8% persistent (coded U09.9 post condition) anosmia, headache, altered status, seizure, which significantly activities daily living, asymptomatic mild hospitalization.12 This guidance statement focuses on PASC, headaches, neuropathies neuropathic pain, muscular pain/weakness tremors, conditions. Fatigue, autonomic dysfunction, cognitive function changes are reviewed separate American Academy Physical Medicine Rehabilitation (AAPM&R) statements.8, 10, 13 addition, AAPM&R consensus document focused currently development. Despite prevalence emerging longevity symptoms, limited exists regarding assessment treatment PASC. Multi-Disciplinary Collaborative (PASC Collaborative), consisting experts PM&R, neurology, internal medicine, family practice, pediatric specialties, cardiology, physical therapy, occupational social work among disciplines, was convened address pressing need iterative, modified Delphi process achieve recommendations series statements prominent symptoms. These informed established centers experience managing PASC.8-10, 13, 14 There intentional focus equity disparities address. Beyond patient care, hope broadened understanding current practices will help identify areas future research. A full description methodology published previously.15 We acknowledge definition evolving, there factors contribute diagnosis management. Literature available our suggested defined persistence beyond 4 onset infection.16 Alternative definitions lasting longer than 3 months.17 World Health Organization "post-COVID condition," describing timing "usually COVID-19" "for least 2 months."18 Based feedback process, we agree earlier evaluation, diagnosis, management improve access beneficial interventions. For purposes statement, recommend expanded if improving 1 month symptom onset. At present, scientific evidence effective limited, prevents creation evidence-based clinical guidelines. intended reflect practice assessment, testing, treatments based expert opinion professionals regularly. It resource concise point reference geared toward clinicians different specialties caring patients. should preclude judgment must applied context specific patient, adjustments preferences, comorbidities, factors. structured first outline evaluation components (Table 1: Initial Evaluation Neurologic Sequelae Patients PASC) 2: Treatment Options Sequelae) review both how consider wide differential possible aspects further diagnostic workup. section dedicated "Red Flag" presentations prompt emergent escalation features Subsequent narrative sections common best Clinicians conduct history predisposing prior relevant hospitalizations, course infection(s), treatments, vaccines/boosters, pertinent history, history. present illness address: those identified new worsening focal deficits, urgent/emergent referral emergency department warranted. (The Red Flags corresponding table provides additional information). Determination neuroimaging individual Consider consultation neurologist imaging testing. Evaluate medication supplement use may impact signs, parameters (i.e., medications adverse side effects, such dry mouth, visual changes, dizziness, and/or sleep/sedation). Include duration helped, worsened, had little no Of note, antihistamine, anticholinergic, antidepressant/anxiolytic, muscle relaxant basic lab workup considered without visit: complete blood count differential; chemistries renal hepatic tests, thyroid stimulating hormone, c-reactive protein, erythrocyte sedimentation rate, vitamins B1, B6, B12, D, magnesium, hemoglobin A1c (HbA1c). Other laboratory autoimmune syndromes, exam, concern comorbid outlined tables follow. return their activities, recommending regular activity tolerated, improved sleep patterns. cautioned avoid rapid overuse triggered exertion. approach recommended ensure flare tolerated. As initially primary clinics. undertake task identifying any ominous particularly reports progressive warrant urgent neurologist, neurosurgeon, findings herald severe, systemic disorder 3: Flags). thorough includes gaining patient's sensory, motor, autonomic, particular attention intervention safety patient. Identification red flag due versus another medical via examination essential. Referral: (ED) neurology depending course/urgency. Action: forced vital appropriate. ED neurosurgery course/urgency associated neuroimaging, Bladder incontinence retention bladder scan, urinalysis, urodynamics, voiding diary, timed Referral cardiology consideration EEG/arrhythmia monitoring. Determine circumstances recent events, certain strenuous, med abnormalities cardiac function—time resolution. Basic tests pituitary adrenal function, inflammation, optimize medications, evaluate safety. Positional—increased intracranial pressure (or low CSF pressure) Worst life (thunderclap headache)–subarachnoid hemorrhage Headache structural affecting brain spinal cord Refer statement. Any (especially rapidly progressive) flag; weakness, deficits indicative diffuse infarct, GBS, neuroimmune concerns trigger workup, could potentially magnetic resonance (MRI) brain, work, cerebrospinal fluid (CSF) studies, electrodiagnostic upper motor neuron hyperreflexia, pathologic clonus reflexes, spasticity, impaired bowel continence, evolving urinary impaction/obstruction processes cord. If vascular (e.g., infarct) neuroinflammatory syndromes transverse myelitis, Neuromyelitis Optica Spectrum Disorder, sclerosis, etc.) Prompt avert catastrophic irreversible central damage.19-23 Acute inflammatory demyelinating polyneuropathy/GBS reported subsequent acutely PASC.22, 23 An nerves, detailed examination, stretch postural reflexes performed. Screening orthostatic hypotension accomplished direct questioning pressures. coexistent especially variation refer dysfunction guidance.13 Neuropsychiatric hallucinations, headaches "thunderclap" addressed. Episodes unexplained loss consciousness more looking underlying arrhythmia seizure disorder. Cranial (refer next Table 4). Symptoms stroke well facial droop, aphasia, unilateral weakness assessed. Assess lateral medullary infarction vertigo, nystagmus, ataxia, nausea vomiting, dysphagia, hiccups. Although ptosis, ophthalmoplegia, diplopia result directly lead blurred vision excluded. example, ophthalmoplegia seen Miller Fisher variant GBS. (ICP) described (headache worse supine position, nausea, status papilledema), worrisome cerebral venous thrombosis; venography computed tomography (CT) venography. New difficulties nature addressed urgently rule out intraocular glaucoma. Signs When appropriate, comorbidities as: Approach: • Recommend avoidance tobacco, alcohol, spicy foods, foods extreme temperature Resources: appropriate: worsen symptoms: angiotensin-converting enzyme (ACE) level; serologies VZV, HSV, EBV PCR (polymerase chain reaction); plasma reagin (RPR); human immunodeficiency virus (HIV); thyroglobulin peroxidase antibodies (TPO TG Ab). neuro-ophthalmology: Signs: studies: conditions: coupled involvement, multidisciplinary encountered clinics serving introduce area followed approaches obtaining histories, conducting therapeutic when specialists broader team. Multiple commonly leads linger PASC.7, 24, 25 One largest evaluating Turkish 356 developed abnormalities, highest involvement (30%), olfactory (27%), glossopharyngeal (25%), vestibulocochlear (17%) though presented neuropathies.26 hypoglossal resistant SARS-CoV-2, lingering (3–60 days) neuropathies, hearing, tinnitus, paresthesia, trigeminal neuralgia. significant difference terms age, gender, body mass index, requirement group unaffected patients.26 Similarly, systematic 56 36 nerves (51%), abducens oculomotor manifesting hypogeusia/ageusia, palsy, ophthalmoparesis.7 bilateral, GBS (MFS). displayed lesions (52%).7 summarized 4. Notably, develop lumbar puncture cytoalbuminologic dissociation GBS/MFS. high level suspicion GBS/MFS intubated where diagnoses easily missed, issues well. Isolated respond favorably steroids, acyclovir/valacyclovir treat reactivated latent neuronal herpes infection. benefit intravenous immunoglobulin exchange.7 Most isolated favorable outcome supportive partial recovery duration. importance proper ongoing properly treated period. post-COVID-19 previously hospitalization.27 meta-analysis ranged 8% 15% 6 infection.27 Post-COVID-19 varied (estimated about 25%) rest having tension-type thunderclap presentations.28 Viral infections known headache.29 factor previous migraine. cumulative lifetime 7.4% males 21% females.30 Three large population-based inverse relationship between household income/education States.30 Persistent phase.31 worsened disturbances, mood loss, fatigue.31 Headaches unique presentation. standardized determine secondary.32 determined headache's phenotype. cognizant secondary disorders. using SNOOP4 tool: see 5: Warning Signals Raise Suspicion Secondary Causes Using Mnemonic cause.33 distinct clearly remembered pain becoming continuous unremitting within 24 hours, over better accounted International Classification Disorders-3 diagnosis.34 typically refractory treatment. describes considerations options types phenotypes Obtain co-occurring (like tension-type, it (space-occupying lesions, infections, abnormalities). SNOOP433 Complete supplements ascertain they might contributing headaches. nonresponsive over-the-counter medications. comorbidities: Nonpharmacologic therapies (acupuncture, relaxation deep breathing exercises, biofeedback) sensitivity, resistance, inability tolerate medication. Ideas include: Medication occurs 15 days develops consequence months. To ergotamines, triptans, opioids, combination analgesics taken 10 simple (acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs) per months.34 biological mechanism maintaining homeostasis, tissue repair, immune regulation, processing/consolidation, quality life.37 Optimal positive results health.38 research 2022, meeting Associated Professional Societies, investigators Cleveland Clinic 41.3% moderate disturbances indicated severe issues. indicates Black three times likely moderate-to-severe recovering anxiety higher-than-average disturbance.39 31 5153 34% 45% 57% depression anxiety.40 noted misalignment sleep–wake cycle circadian rhythms negatively affect attention, concentration, learning, memory, some PASC.41 Management insomnia requires stepwise approach, beginning attempts eliminate minimize obstructive apnea, interfere optimal sleep. 7 considerations. Successful behavioral pharmacologic devised recognized PASC-associated entered into chronic insomnia. preferred line therapy (CBT-I), multicomponent targeting cognitions behavior poor Behaviorally, encouraged maintain consistent routine establishing stable bed wake time, try lie sleeping, sleeping environment comfort, substances sleep, reduce (sleep restriction), get experiencing anxiety. CBT-I addresses anxious thoughts surrounding sleeplessness, expectations, insomnia, promotes relaxation, mindfulness, meditation. validated face-to-face remote applications (such online teletherapy) shown promising small studies.42 of: sleep: Clinician prescription guided effects cautiously. accessible many, either lack therapists, limitations insurance, time. cases, short acceptable thoroughly evaluated beforehand, regularly treatment, continues positively diary very helpful tool gain insight problems, monitor whether successful. diaries normally completed once twice day. usually consists several questions related times, nap caffeine alcohol use, general functioning. (less month) stressors causes. However, fails substantial distress, short-term warranted immediate interference daytime control escalating Interventions, tailored polypharmacy elderly dosing pregnant lactating women considered. Social determinants (SDOH) instance, someone lives crowded multigenerational home works night shift difficulty quantity 8 examples SDOH 8: Equity Considerations Examples PASC: Sequelae). Racial/Ethnic Minority Groups Example: People (including African-American), American-Indian/Alaska Native, Pacific Islander, Asian-American, Mixed Race, Latino/Hispanic (ethnicity) Individuals racial/ethnic minority groups lower rates rehabilitation classified White/Caucasian.47, 48 All impairment symptomatology tremor, vestibular complaints, paresis specialized neurorehabilitation programs. Referrals timely manner. Treating physicians what type interventions programs considering cost accessibility. Every effort made close gaps groups. Biologic Sex Female adults Biologically female differences diagnoses. hormone levels estrogen)

Language: Английский

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Endothelial Extracellular Vesicles Enriched in microRNA-34a Predict New-Onset Diabetes in Coronavirus Disease 2019 (COVID-19) Patients: Novel Insights for Long COVID Metabolic Sequelae

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 389(1), P. 34 - 39

Published: Feb. 9, 2024

Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it known presence of other metabolic alterations poses a considerably high risk to develop severe COVID-19; 2) patients who survived acute respiratory syndrome 2 (SARS-CoV-2) infection have an increased developing new-onset diabetes. However, mechanisms underlying this association are mostly unknown, there no reliable biomarkers predict development In present study, we demonstrate specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts COVID-19. This was independent age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, D-dimer. SIGNIFICANCE STATEMENT: We for first time able after having contracted (COVID-19). Our findings also relevant when considering emerging importance post-acute sequelae COVID-19, with systemic manifestations observed even months viral negativization (long COVID).

Language: Английский

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Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach

Diseases, Journal Year: 2024, Volume and Issue: 12(5), P. 95 - 95

Published: May 6, 2024

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, outcomes persistent COVID-19 symptoms in encompassing vulnerable populations, such as pregnant women oncological patients. Our objective is to emphasize critical significance adopting an integrated approach for early detection appropriate management long COVID. The incidence severity can significant impact on quality life patients course disease case pre-existing pathologies. Particularly, fragile patients, presence PASC related significantly worse survival, independent from vulnerabilities treatment. It important try achieve recognition management. Various mechanisms are implicated, resulting wide range presentations. Understanding specific factors involved crucial tailoring effective interventions support strategies. Management approaches involve biopsychosocial assessments treatment comorbidities, autonomic dysfunction, well multidisciplinary rehabilitation. overall one gradual improvement, with recovery observed majority, though not all, As research long-COVID continues evolve, ongoing studies likely shed more light intricate relationship between chronic diseases, status, cardiovascular psychiatric disorders, effects This information could guide healthcare providers, researchers, policymakers developing targeted interventions.

Language: Английский

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Editorial: Obesity, metabolic phenotypes and COVID-19

Metabolism, Journal Year: 2022, Volume and Issue: 128, P. 155121 - 155121

Published: Jan. 10, 2022

Language: Английский

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Long-COVID, Metabolic and Endocrine Disease

Hormone and Metabolic Research, Journal Year: 2022, Volume and Issue: 54(08), P. 562 - 566

Published: June 20, 2022

In the aftermath of corona pandemic, long-COVID or post-acute COVID-19 syndrome still represents a great challenge, and this topic will continue to represent significant health problem in coming years. At present, impact on our system cannot be fully assessed but according current studies, up 40% people who have been infected with SARS-CoV-2 suffer from clinically relevant symptoms several weeks months after acute phase. The main are chronic fatigue, dyspnea, various cognitive symptoms. Initial studies shown that overweight diabetes mellitus higher risk developing associated Furthermore, repeated treatment steroids can contribute long-term metabolic endocrine disorders. Therefore, structured program rehabilitation physical activity as well optimal dietary management is utmost importance, especially for patients diseases and/or long-COVID. removal autoantibodies specific therapeutic apheresis procedures could lead improvement individual patients.

Language: Английский

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