Tag: long covid neurology

Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome – a case-control study

Abstract:

Purpose: Eighty percent of patients infected by SARS-CoV-2 report persistence of one symptom beyond the 4-week convalescent period. Those with orthostatic tachycardia and orthostatic symptoms mimicking postural tachycardia syndrome, they are defined as Long-COVID POTS [LCP]. This case-control study investigated potential differences in autonomic cardiovascular regulation between LCP patients and healthy controls.

Methods: Thirteen LCP and 16 healthy controls, all female subjects, were studied without medications. Continuous blood pressure and ECG were recorded during orthostatic stress test, respiratory sinus arrhythmia, and Valsalva maneuver. Time domain and power spectral analysis of heart rate [HR] and systolic blood pressure [SBP] variability were computed characterizing cardiac autonomic control and sympathetic peripheral vasoconstriction.

Results: LCP had higher deltaHR (+ 40 ± 6 vs. + 21 ± 3 bpm, p = 0.004) and deltaSBP (+ 8 ± 4 vs. -1 ± 2 mmHg, p = 0.04) upon standing; 47% had impaired Valsalva maneuver ratio compared with 6.2% in controls (p = 0.01). Spectral analysis revealed that LCP had lower RMSSD (32.1 ± 4.6 vs. 48.9 ± 6.8 ms, p = 0.04) and HFRRI, both in absolute (349 ± 105 vs. 851 ± 253ms2, p = 0.03) and normalized units (32 ± 4 vs. 46 ± 4 n.u., p = 0.02). LFSBP was similar between groups.

Conclusions: LCP have reduced cardiovagal modulation, but normal sympathetic cardiac and vasoconstrictive functions. Impaired parasympathetic function may contribute to the pathogenesis of Long-COVID POTS syndrome.

Source: Rigo S, Urechie V, Diedrich A, Okamoto LE, Biaggioni I, Shibao CA. Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome – a case-control study. Bioelectron Med. 2023 Sep 6;9(1):19. doi: 10.1186/s42234-023-00121-6. PMID: 37670400; PMCID: PMC10481607. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481607/ (Full text)

Efficiency of comprehensive rehabilitation of chronic fatigue syndrome due to coronavirus infections COVID-19

Abstract:

The aim of the study was to study the effectiveness of complex rehabilitation in patients with chronic fatigue syndrome caused by coronavirus infections.

In 120 patients with a confirmed diagnosis of SARS-CoV-2 (COVID-19) aged 20-58 years, post-COVID syndrome or chronic fatigue syndrome was detected, 52 men and 68 women. Patients had asthenic, cognitive, vegetative manifestations, sleep disorders, smell and taste disorders, anxiety and depression.

Patients received drug therapy: succinic acid preparations, brain metabolic drugs, stimulating antidepressants, sleeping pills – melatonin and B vitamins, among other things, received micropolarization of the head and translingualneurostimulation.

The results of treatment confirmed the effectiveness of the proposed conservative therapy. The neurological symptoms of post-COVID syndrome – chronic fatigue syndrome (CFS) were studied in 120 patients with a confirmed diagnosis of SARS-CoV-2 (COVID-19), aged 20-58 years.

Patients were examined according to the “Questionnaire for the detection of asthenia”, “Mini Mental State Assessment (MMSE)”, et.al. Sleep disorders were studied using the Epworth Sleepiness Scale, anxiety and depression were studied using the “Questionnaire for Determining Anxiety and Depression”.

The patients were divided into 2 groups: the main group (MG) – 69 patients and the control group (CG) – 51 patients. Patients with MG and CG received drug therapy: succinic acid preparations, brain metabolic drugs, stimulating antidepressants, sleeping pills – melatonin and B vitamins. And patients with MG, among other things, received micropolarization of the head and translingualneurostimulation.

Source: Z.I. Adambaev, I.A. Kilichev, A.B. Nurzhonov, N.Yu. Khudoyberganov, and M.R. Niyazmetov. Efficiency of comprehensive rehabilitation of chronic fatigue syndrome due to coronavirus infections COVID-19. BIO Web of Conferences 65, 05039 (2023) https://www.bio-conferences.org/articles/bioconf/abs/2023/10/bioconf_ebwff2023_05039/bioconf_ebwff2023_05039.html (Full text available as PDF file)

Severity of neurological long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors

Abstract:

Background: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting.

Methods: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies towards the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires.

Results: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10−9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ −0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087).

Conclusions: Concentrations of autoantibodies correlates to intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.

Source: Felix S. Seibert, Ulrik Stervbo, Lea Wiemers, Sarah Skrzypczyk, Maximillian Hogeweg, Sebastian Bertram, Julia Kurek, Moritz Anft, Timm H. Westhoff, Nina Babel. Severity of neurological long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors. Autoimmunity Reviews,2023, 103445, ISSN 1568-9972. https://www.sciencedirect.com/science/article/abs/pii/S1568997223001799 (Full text)

The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog

Abstract:

Post-COVID-19 condition (commonly known as Long COVID) is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. Cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of the pathophysiology of Post-COVID-19 condition (PCC).

Given the substantial lack of specific drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes, which have been on the market for several years as adjuvant therapy for cerebral metabolic alterations resulting from neuroendocrine disorders, might represent a potential option in an overall therapeutic strategy that aims to control PCC-associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their potential effectiveness in PCC. Our initial clinical experience seems to corroborate this rationale. Further controlled clinical research is warranted in order to verify this hypothesis.

Source: Menichetti F. The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog. J Clin Med. 2023 Aug 23;12(17):5478. doi: 10.3390/jcm12175478. PMID: 37685544; PMCID: PMC10488182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488182/ (Full text)

SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19

Abstract:

Background and objectives: Millions of Americans were exposed to SARS-CoV-2 early in the pandemic but could not get diagnosed with COVID-19 due to testing limitations. Many have developed a postviral syndrome (PVS) including neurologic manifestations similar to those with postacute sequelae of SARS-CoV-2 infection (Neuro-PASC). Owing to those circumstances, proof of SARS-CoV-2 infection was not required for evaluation at Northwestern Medicine’s Neuro COVID-19 clinic. We sought to investigate clinical and immunologic findings suggestive of SARS-CoV-2 exposure in patients with PVS.

Methods: We measured SARS-CoV-2-specific humoral and cell-mediated immune responses against Nucleocapsid and Spike proteins in 29 patients with PVS after suspected COVID-19, 32 confirmed age-matched/sex-matched Neuro-PASC (NP) patients, and 18 unexposed healthy controls. Neurologic symptoms and signs, comorbidities, quality of life, and cognitive testing data collected during clinic visits were studied retrospectively.

Results: Of 29 patients with PVS, 12 (41%) had detectable humoral or cellular immune responses consistent with prior exposure to SARS-CoV-2. Of 12 PVS responders (PVS+), 75% harbored anti-Nucleocapsid and 50% harbored anti-Spike responses. Patients with PVS+ had similar neurologic symptoms as patients with NP, but clinic evaluation occurred 5.3 months later from the time of symptom onset (10.7 vs 5.4 months; p = 0.0006). Patients with PVS+ and NP had similar subjective impairments in quality of life measures including cognitive function and fatigue. Patients with PVS+ had similar results in objective cognitive measures of processing speed, attention, and executive function and better results in working memory than patients with NP.

Discussion: Antibody and T-cell assays showed evidence of prior SARS-CoV-2 exposure in approximately 40% of the PVS group. Three-quarters of patients with PVS+ had detectable anti-Nucleocapsid and one-half anti-Spike responses, highlighting the importance of multitargeted COVID-19 immunologic evaluation and the limitations of commercially available diagnostic tests. Despite their persistent symptoms, lack of COVID-19 diagnosis likely delayed clinical care in patients with PVS. Our data suggest that millions of Americans presenting with PVS resembling Neuro-PASC were indeed exposed to SARS-CoV-2 at the beginning of the pandemic, and they deserve the same access to care and inclusion in research studies as patients with NP with confirmed COVID-19 diagnosis.

Source:Orban ZS, Visvabharathy L, Perez Giraldo GS, Jimenez M, Koralnik IJ. SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19. Neurol Neuroimmunol Neuroinflamm. 2023 Aug 23;10(6):e200159. doi: 10.1212/NXI.0000000000200159. PMID: 37612134; PMCID: PMC10448973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448973/ (Full text)

The effects of COVID-19 on cognitive performance in a community-based cohort: a COVID symptom study biobank prospective cohort study

Abstract:

Background: Cognitive impairment has been reported after many types of infection, including SARS-CoV-2. Whether deficits following SARS-CoV-2 improve over time is unclear. Studies to date have focused on hospitalised individuals with up to a year follow-up. The presence, magnitude, persistence and correlations of effects in community-based cases remain relatively unexplored.

Methods: Cognitive performance (working memory, attention, reasoning, motor control) was assessed in a prospective cohort study of participants from the United Kingdom COVID Symptom Study Biobank between July 12, 2021 and August 27, 2021 (Round 1), and between April 28, 2022 and June 21, 2022 (Round 2). Participants, recruited from the COVID Symptom Study smartphone app, comprised individuals with and without SARS-CoV-2 infection and varying symptom duration. Effects of COVID-19 exposures on cognitive accuracy and reaction time scores were estimated using multivariable ordinary least squares linear regression models weighted for inverse probability of participation, adjusting for potential confounders and mediators. The role of ongoing symptoms after COVID-19 infection was examined stratifying for self-perceived recovery. Longitudinal analysis assessed change in cognitive performance between rounds.

Findings: 3335 individuals completed Round 1, of whom 1768 also completed Round 2. At Round 1, individuals with previous positive SARS-CoV-2 tests had lower cognitive accuracy (N = 1737, β = -0.14 standard deviations, SDs, 95% confidence intervals, CI: -0.21, -0.07) than negative controls. Deficits were largest for positive individuals with ≥12 weeks of symptoms (N = 495, β = -0.22 SDs, 95% CI: -0.35, -0.09). Effects were comparable to hospital presentation during illness (N = 281, β = -0.31 SDs, 95% CI: -0.44, -0.18), and 10 years age difference (60-70 years vs. 50-60 years, β = -0.21 SDs, 95% CI: -0.30, -0.13) in the whole study population. Stratification by self-reported recovery revealed that deficits were only detectable in SARS-CoV-2 positive individuals who did not feel recovered from COVID-19, whereas individuals who reported full recovery showed no deficits. Longitudinal analysis showed no evidence of cognitive change over time, suggesting that cognitive deficits for affected individuals persisted at almost 2 years since initial infection.

Interpretation: Cognitive deficits following SARS-CoV-2 infection were detectable nearly two years post infection, and largest for individuals with longer symptom durations, ongoing symptoms, and/or more severe infection. However, no such deficits were detected in individuals who reported full recovery from COVID-19. Further work is needed to monitor and develop understanding of recovery mechanisms for those with ongoing symptoms.

Source: Cheetham NJ, Penfold R, Giunchiglia V, Bowyer V, Sudre CH, Canas LS, Deng J, Murray B, Kerfoot E, Antonelli M, Rjoob K, Molteni E, Österdahl MF, Harvey NR, Trender WR, Malim MH, Doores KJ, Hellyer PJ, Modat M, Hammers A, Ourselin S, Duncan EL, Hampshire A, Steves CJ. The effects of COVID-19 on cognitive performance in a community-based cohort: a COVID symptom study biobank prospective cohort study. EClinicalMedicine. 2023 Jul 21;62:102086. doi: 10.1016/j.eclinm.2023.102086. PMID: 37654669; PMCID: PMC10466229. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466229/ (Full text)

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization

Abstract:

Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown.

In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19.

A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety.

Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

Source: Taquet, M., Skorniewska, Z., Hampshire, A. et al. Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization. Nat Med (2023). https://doi.org/10.1038/s41591-023-02525-y https://www.nature.com/articles/s41591-023-02525-y (Full text)

Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review

Summary:

  • Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware.
  • The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease.
  • Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain–Barré syndrome, and cerebrovascular disease.
  • Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease.
  • Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19.
  • The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance.

Source: Wesselingh, R. (2023), Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review. Med J Aust. https://doi.org/10.5694/mja2.52063 https://onlinelibrary.wiley.com/doi/10.5694/mja2.52063 (Full text available as PDF file)

 

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Abstract:

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome.

Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.

Source: Brown R L, Benjamin L, Lunn M P, Bharucha T, Zandi M S, Hoskote C et al. Pathophysiology, diagnosis, and management of neuroinflammation in covid-19 BMJ 2023; 382 :e073923 doi:10.1136/bmj-2022-073923 https://www.bmj.com/content/382/bmj-2022-073923.abstract (Full text available as PDF file)

Evaluation of Post–COVID-19 Cognitive Dysfunction: Recommendations for Researchers

Opinion:

SARS-CoV-2 infection is associated with increased rates of postillness cognitive dysfunction, colloquially referred to as “brain fog,”1 that may portend significant consequences for patient functioning and quality of life. Post–COVID-19 cognitive dysfunction is 1 of approximately 200 symptoms of post–COVID-19 condition (PCC), defined by the World Health Organization as developing within 3 months of an initial SARS-CoV-2 infection, lasting at least 2 months, and cannot be explained by an alternative diagnosis. A pooled analysis of 54 studies and 1.2 million individuals found that 3.2% of patients’ self-reported cognitive problems 3 months after symptomatic infection,1 while other studies have shown objective evidence of cognitive dysfunction in approximately 24% of patients nearly 1 year later.2 Accumulating evidence also supports the hypothesis that COVID-19 may increase risk for later neurodegeneration3 and exacerbate preexisting cognitive dysfunction.4 As one of the most common symptoms of PCC and one for which affected individuals may seek accommodations and disability benefits in accordance with the Americans With Disabilities Act, it is imperative that we use more rigorous studies of cognitive outcomes. Accordingly, the following recommendations have been generated by members of the NeuroCOVID International Neuropsychology Taskforce based on initial guidelines.5

Source: Jaqueline H. Becker, PhD; Tracy D. Vannorsdall, PhD; Sara L. Weisenbach, PhD. JAMA Psychiatry. Published online August 16, 2023. doi:10.1001/jamapsychiatry.2023.2820 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2808155