Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

Pharmacological Research, Journal Year: 2022, Volume and Issue: 183, P. 106360 - 106360

Published: July 19, 2022

Language: Английский

---

Post-COVID syndrome

Deutsches Ärzteblatt international, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 10, 2023

As defined by the WHO, term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following acute phase SARS-CoV-2 infection and as consequence thereof. PCS is found mainly in adults, less frequently children adolescents. It develop both patients who initially had only mild or none at all those severe course coronavirus disease 2019 (COVID-19).The data presented here were derived from systematic literature review.PCS occurs up to 15% unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased most recent pandemic lower after vaccination. pathogenesis not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), persistence virus are thought be causative. Owing broad viral tropism, different organs involved vary. To date, there hardly any evidence-based recommendations for definitive diagnosis its treatment.The gaps our knowledge mean better documentation necessary compile on which early detection, diagnosis, treatment based. ensure best possible care PCS, regional centers networks embracing existing structures healthcare system sectors providers should set structured algorithms established. Given sometimes serious consequences affected, it seems advisable keep number infections low protective measures tailored prevailing situation.

Language: Английский

---

Thromboinflammation in long COVID—the elusive key to postinfection sequelae?

Journal of Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 21(8), P. 2020 - 2031

Published: May 11, 2023

Language: Английский

---

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with virus, a significant proportion them continue to experience issues weeks, months even years acute infection SARS-CoV-2. This persistence clinical symptoms in individuals for at least three onset or emergence new lasting more than two months, without any other explanation alternative diagnosis have named long COVID, long-haul post-COVID-19 conditions, chronic post-acute sequelae (PASC). Long COVID characterized constellation disorders that vary widely their manifestations. Further, mechanisms underlying are not fully understood, which hamper efficient treatment options. review describes predictors common related COVID's effects on central peripheral nervous system organs tissues. Furthermore, transcriptional markers, molecular signaling pathways risk factors such sex, age, pre-existing condition, hospitalization during phase COVID-19, vaccination, lifestyle presented. Finally, recommendations patient rehabilitation management, well therapeutical approaches discussed. Understanding complexity this disease, its across multiple organ systems overlapping pathologies possible paramount developing diagnostic tools treatments.

Language: Английский

---

Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Language: Английский

---

Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long‐term outcomes in COVID‐19 patients

American Journal of Hematology, Journal Year: 2022, Volume and Issue: 97(7), P. 915 - 923

Published: April 28, 2022

Abstract Sustained hypercoagulability and endotheliopathy are present in convalescent COVID‐19 patients for up to 4 months from recovery. The hemostatic, endothelial, inflammatory profiles of 39 recovered were evaluated 16 after recovery COVID‐19. These values compared with a control group healthy volunteers ( n = 124). (71.8% males, median age 43 years) reviewed at mean 12.7 ± 3.6 following One patient without cardiovascular risk factors had post acute ischaemic limb. Elevated D‐dimer Factor VIII levels above normal ranges noted 17.9% (7/39) 48.7% (19/39) respectively, higher 0.34 FEU μg/mL (IQR 0.28, 0.46) p < .001) 150% 171, 203) .004), versus controls. Thrombin generation (Thromboscreen) showed endogenous thrombin potential (ETP) 1352 nM*min 1152, 1490) .002) peak height 221.4 nM 170.2, 280.4) 0.01) delayed lag time 2.4 min (1.42–2.97) 0.0002) Raised vWF:Ag ICAM‐1 observed 7.7% (3/39) VWF:Ag 117% 86, 154) 0.02) 54.1 ng/mL 43.8, 64.1) .004) than IL‐6 was be raised 35.9% (14/39) patients, 1.5 pg/mL 0.6, 3.0) 0.004) Subgroup analysis stratifying by severity vaccination preceding SARS‐CoV‐2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, inflammation still detectable some approximately 1 year

Language: Английский

---

Persistent capillary rarefication in long COVID syndrome

Angiogenesis, Journal Year: 2022, Volume and Issue: 26(1), P. 53 - 61

Published: Aug. 11, 2022

Abstract Background Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after initial infection. Methods This prospective, observational study included 58 participants, 27 whom were long COVID with > 12 weeks recovery PCR-confirmed SARS-CoV-2 Fifteen healthy volunteers historical cohort critically ill COVID-19 ( n = 16) served controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version Glycocheck™ software was used quantify density, perfused boundary region (PBR-an inverse variable endothelial glycocalyx dimensions), red blood cell velocity (VRBC) microvascular health score (MVHS™) in microvessels diameters 4–25 µm. Measurements main results Although dimensions comparable those controls, µm-precise analysis showed significant decrease that exclusively affected very small capillaries (D5: − 45.16%; D6: 35.60%; D7: 22.79%). Plotting VRBC feed vessels number did not respond adequately local variations tissue metabolic demand. MVHS markedly reduced (healthy 3.87 vs. 2.72 points; p 0.002). Conclusions Our current data strongly suggest leaves capillary rarefication 18 Whether, what extent, when observed damage might be reversible remains unclear.

Language: Английский

---

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach

Medicina, Journal Year: 2022, Volume and Issue: 58(3), P. 419 - 419

Published: March 12, 2022

Dyspnea, shortness of breath, and chest pain are frequent symptoms post-COVID syndrome (PCS). These unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause exercise-induced dyspnea PCS. Since there is broad overlap symptomatology with myalgic encephalomyelitis/chronic fatigue (ME/CFS), causes for potential consequences can be deduced by stringent application assumptions made ME/CFS our recent review papers. One the first stimuli respiration exercise caused metabolic feedback via skeletal muscle afferents. PCS, which occurs early on during exercise, arise from combined disturbance poor energetic situation autonomic dysfunction (overshooting respiratory response), both found ME/CFS. The exaggerated response aggravating does not only limit ability but further impairs muscular situation: one buffering mechanisms alkalosis proton shift intracellular extracellular space sodium–proton-exchanger subtype 1 (NHE1), thereby loading cells sodium. This adds two other sodium already operative, namely glycolytic metabolism (intracellular acidosis) impaired Na+/K+ATPase activity. High unfavorable effects mitochondrial calcium sodium–calcium-exchangers (NCX). Mitochondrial overload high reversing transport mode NCX import key driver chronification. Prevention hyperventilation therapeutic keeping below threshold where occurs.

Language: Английский

---

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

PM&R, Journal Year: 2022, Volume and Issue: 14(10), P. 1270 - 1291

Published: Sept. 28, 2022

Although many people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recover completely, others are left long-lasting symptoms that persist for at least 4 weeks, a condition referred to by the National Institutes of Health (NIH) as post-acute sequelae SARS-CoV-2 infection (PASC).1 The Centers Disease Control and Prevention (CDC) defines post-COVID (coronavirus disease) conditions wide range health consequences present four or more weeks after SARS-CoV-2,2 whereas World Organization (WHO) refers beyond 12 an initial infection, last months, cannot be explained alternative diagnosis.3 There number terms found in literature describe this (e.g., long COVID, persisting post-COVID, COVID-19, long-haul others), but purposes statement, term PASC is used. can non-specific constellation signs symptoms,4 some which appear autonomic nature. These include, not limited to, orthostatic intolerance, palpitations, tachycardia, syncope, hypertension, labile blood pressures, dizziness, fatigue, exercise intolerance.5 most common diagnoses associated intolerance postural tachycardia (POTS), often follow viral infection.5 Other features may related dysfunction include cognitive impairment (often called "brain fog"), headache, insomnia, neuropathic pain, gastrointestinal genitourinary dysfunction, allergic suggestive mast cell activation, such pruritis, urticaria, flushing, angioedema, wheezing, food sensitivities, others.6 mechanisms general being investigated, several possible etiologies have been proposed including autoimmunity, inflammation, persistent T-cell abnormalities, endothelial prothrombotic state, small fiber neuropathy, others.5, 7-12 Data released CDC demonstrate one five adults (19%) who had COVID past still has "long COVID," overall, 1 13 United States (7.5%) COVID" symptoms.13 Estimates Kingdom (UK) suggest ~3% UK population experiencing infection.14 Despite prevalence prolonged emerging data on various manifestations mechanisms, guidance exists regarding assessment treatment broad symptoms, due PASC. With mind, American Academy Physical Medicine Rehabilitation (AAPM&R) Multi-Disciplinary Collaborative (PASC Collaborative) was convened address urgent need interim care patients This document part larger series addressing PASC, specifically discusses dysfunction. Fatigue, sequalae, cardiovascular complications discussed elsewhere.15-18 created, part, develop expert recommendations from established centers extensive experience managing composed 41 post-COVID-19 centers, first were April June 2020. following iterative modified Delphi approach achieve consensus statements focused prominent symptoms.15-18 full description process published detail previously.19 At present, scientific evidence effective limited, prevents creation evidence-based clinical guidelines. developed diverse team experts, patient input, integrate current expertise available provide tools clinicians treating patients. intentional focus equity disparities outcomes critically important address. Beyond offering based presenting hope broadened understanding practices will help identify areas future research. We acknowledge definition evolving there factors contribute diagnosis. In addition, likely encompasses different subtypes, overlapping features. As such, intended audiences could span primary clinicians, physical medicine rehabilitation physicians, other specialists. statement reflect practice assessment, testing, treatment, acknowledging paucity diagnosis we recognize shortage specialists States, limit access specialized evaluation testing time development early vaccinated, incidence trajectory vaccinated "breakthrough" cases (including variants virus) evolving. considered these issues during process, generally apply individuals regardless their vaccination status. It note provided should preclude judgment must applied context specific patient, adjustments preferences, comorbidities, factors. any plan, encouraged discuss unknowns ambiguities diagnosis, prognosis, well benefits risks interventions. recognizes typically cluster multiple body systems overlap pulmonary necessarily suggested treatments covered separate statements.15-18 use "autonomic dysfunction" refer disturbance nervous system, disorders, neurocardiogenic syncope (NCS) also known vasovagal hypotension (OH), inappropriate sinus (IST). Orthostatic (OI) used when objective tests do confirm disorders setting precipitated upright position relieved recumbency. diagnostic criteria POTS, NCS, OH, IST outlined Table 1.20-22 Based discussion feedback arrived utilized practitioners evaluating PASC-related encourage utilize because evaluation, management ultimately improve functional reduce disability system (ANS) consists sympathetic, parasympathetic, enteric divisions responsible numerous physiologic functions, control heart rate pressure, gastric motility secretion, bladder function, respiration, temperature control, distribution flow organs tissue. ANS mediates "flight fight" response both external internal stimuli order maintain homeostasis.23 intimately involved vagus nerve, carries parasympathetic output, major constituent neural reflex mechanism—the inflammatory reflex—that controls innate immune responses inflammation pathogen invasion tissue injury.24 To end, sympathetic overactivity pro-inflammatory while increased activity anti-inflammatory properties.25 Autonomic manifestations, resting frequently reported SARS CoV-2 infection.26, 27 lightheadedness, presyncope, fatigue. Gastrointestinal, respiratory, (see 2). New-onset variety bacterial infections, influenza, Epstein–Barr virus, Borrelia burgdorferi.6, 28 Case reports described OI, IST, neuropathy (AN) POTS disorder observed.29-31 OI commonly diagnosed consistent meet POTS.32 varying rates PASC; international online survey 802 19% having received POTS.33 studies estimate 25%34 upward 40% 69% PASC.32 Given between Society (AAS) research funding investigate resources new-onset infection.35 Considering challenge. offer history, exam, laboratory tests, investigations aid 3). Clinicians conduct history review predisposing prior relevant hospitalizations, timeline symptom evolution address: neurologic sensory exam look (particularly loss pinprick sensation) evaluate perform 10-min stand test recording pressure supine standing 3, 5, 7 10 min. Consider obtaining tilt table symptomatic negative consider pulse oximetry rest exertion/activity rule out hypoxemia, ECG, echocardiogram, ambulatory cardiac monitoring with: Further warranted per Cardiovascular Complications Consensus Guidance Statement18 Because disabling fatigue (Table onset relation recorded modes onset: (1) resolution infection; (2) within subacute period (days weeks) recovery (3) delayed onset, 3 months infection. Review course hospitalization, medications side effects—such tachycardia—and personal family autoimmune obtained. hallmark disorders. affect systems, thorough needed whether it causing. From perspective, crucial understand how patients' affecting ability function participate home, community, work activities. notable significant cardiopulmonary chest pain shortness breath require differentiation therapeutic approaches. If abnormalities electrocardiogram (ECG), 24-hour Holter monitor, noted if high suspicion disease obtain before disorder. our experience, dual workup treatment. Similarly, anxiety, although anxiety neuropsychiatric occur attribute those generalized depression, panic disorder, lead missed opportunity study, unrelated COVID-19 75% misdiagnosed physician POTS. same study respondents, 77% (n = 3471) encountered psychiatric psychological problem they POTS.36 Many PASC.37 A sensation recommended neuropathy. potential abnormal pupillary dilated pupils poorly responsive light, acrocyanosis—a purplish-blue discoloration lower extremities due, pooling.38 Acrocyanosis Raynaud's disease, connective erythromelalgia sometimes point toward etiology.39 Assessment joint hypermobility Beighton scale new pre-existing spectrum hypermobile Ehlers-Danlos (EDS), highly prevalent disorders.40 dermographism skin examination hyperactivity, accompany EDS, PASC.11, 10-minute confirms 1) then no further confirmation via necessary. inconclusive unremarkable section tests). take into consideration generated wearable devices monitors (Apple watch, Fitbit similar devices) patient's self-obtained performed home. in-office inconclusive. Note variable results depending day, appointment, hydration status, When uncertain, progressing, cardiovascular, neurologic, gastrointestinal, referral specialist considered. prioritize persons provides summary what about populations considerations populations. cause Parkinson sclerosis, spinal cord injury, traumatic brain diabetes mellitus.41 Depending status individual, modifications required office setting. For example, impaired mobility, injury unable complete test; therefore, special accommodations usual protocols Disability Example: People certain SCI sitting maneuvers). Thus, underlying requires careful consideration.43, 44 increasing fluids frequency intermittent catheterization. Exercise prescriptions account paralysis, heterotopic ossification rotator cuff dysfunction) complicated medical combined longer visits personnel PM&R nurses, therapists, psychologists, social workers) deliver optimal care35 Obesity overweight/obese Racial/Ethnic Minority Groups Black African-American), American-Indian/Alaska Native, Pacific Islander, Asian-American, Mixed Race, and/or Latino/Hispanic (ethnicity) Biologic Sex Pregnancy Among awareness recognition conditions, inclusive ideally managed physicians heterogeneity implement tailored approach.56 Enhancing education delays outcomes. aware implicit (unconscious) sex-related bias add challenges female another dysfunction; importantly, misdiagnosis common57 pregnant individuals, interventions prescriptions, carefully prescribed individual's tolerate safety intervention person. Symptoms pregnancy consistently predicted (perhaps counterintuitively) worse trimester weight gain, balance problems (all prescriptions) trimester.53 Diagnostic using radiation x-ray computed tomography) usually contraindicated. contraindicated (and breastfeeding) caution advised Insurance Individuals uninsured, underinsured, afford healthcare services cost value in/out conditions. Treatment interventions, therapy, copayments deductibles, even insurance. specialty clinic guided recommendation 3).5 Social community groups assist finding local support During pandemic, broadening insurance coverage telemedicine services, telephone virtual online—leading greater services. Telerehabilitation evolving,58 relatively satisfaction physiatry59 therapy visits60 Physicians advocating behalf immunotherapy actively engaging appeal deny therapy61 Laboratory count (CBC), comprehensive metabolic panel (CMP), thyroid (TFTs).62 Common vitamin nutritional deficiencies iron deficiency without anemia mild B12 deficiency.63, 64 Vitamin serum ferritin level obtained, supplementation noted. Additional morning cortisol assess adrenal insufficiency contributing low pressure. assessing basic markers autoimmunity,65, 66 antinuclear antibody (ANA), erythrocyte sedimentation (ESR), C-reactive protein (CRP), particularly conjunction dyspnea, d-dimer embolism, especially given association thromboembolic events.67 warrant investigation. suspected previous test, unrevealing, situations where unclear progressive refractory specialist. under specialist) deep breathing Valsalva maneuver, quantitative sudomotor axon (QSART), thermoregulatory sweat biopsy neuropathy.38 laboratories equipped throughout country, barrier Tilt test. Patients laid tilted 60 70 degrees minutes monitored peripheral arterial volume-clamp measurements, confirmed automated sphygmomanometer over brachial artery, allowing continuous beat-to-beat head-up tilt. possible, all held half-lives minimize blunting vital sign responses. useful delineate etiology undiagnosed episodes altered consciousness differentiate anoxic epilepsy pseudo-seizures. Compared active standing, activates skeletal muscles compress veins increase venous return, passive induces stress body, thus sensitive eliciting hypotension, exaggerated neurally mediated hypotension. clinician observe real-time changes elicited psychogenic pseudo-syncope does yield definite diagnosis.68, 69 Deep slow, breaths six breaths/minute position. assesses integrity cardiovagal reflexes system. Heart single-lead difference end expiration inspiration calculated (maximum-minimum rate). An result defined maximum-minimum less than 5th percentile age- sex-adjusted normative data,70 Less 10% deep-breathing test.28 maneuver forceful attempt exhalation against closed airway Like breathing, effects gravitational stress. coached forcefully exhale 40 mm Hg glottis seconds bugle-type mouth piece. Blood continuously testing. Analysis evaluates adrenergic analysis function. phases only late phase II IV evaluated baroreflex Specifically, overshoot expected, represent vasoconstriction outflow. normal, exhibit hyperdynamic hypersensitivity hyperadrenergic state.38 Quantitative (or QSART) post-ganglionic (sweat) stimulation nerves. QSART 33% 63% POTS.38 Thermoregulatory TST) pre- functions elevation core temperature. indicate distinct patterns neurodegenerative pure failure, atrophy, diabetic ganglionopathy. Abnormal TST seen half predominantly distal pattern.28, 38 Skin minimally invasive procedure punch kit. Obtained proximal leg, epidermal nerve gland densities. Decreased density decreased echocardiography, rather recommend separately

Language: Английский

---

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(16), P. 1653 - 1708

Published: Aug. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Language: Английский

---