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1.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.12.18.23299958

ABSTRACT

PurposeOrthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with symptoms and comorbidities. MethodsParticipants were recruited from 8 UK long covid clinics, and healthy volunteers from general population. All undertook standardised National Aeronautics and Space Administration Lean Test (NLT). Participants history of typical OI symptoms (e.g. dizziness, palpitations) prior to and during the NLT were recorded. Results277 long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or PoTS, 10% had asymptomatic OH. 130 (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. 41 (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive to one reading, resulted in 11% of long covid participants meeting criteria for PoTS, but not in healthy volunteers. ConclusionMore than half of long covid patients experienced OI symptoms during NLT and more than one in ten patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced. Trial registration numbers NCT05057260, ISRCTN15022307


Subject(s)
Hypotension, Orthostatic , Dizziness , Postural Orthostatic Tachycardia Syndrome , Osteogenesis Imperfecta , Orthostatic Intolerance
2.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.17.23294204

ABSTRACT

Background Exercise-based treatments can be harmful in people who were SARS-CoV-2 positive and living with post-COVID-19 condition (PL-PCC) and who have post-exertional malaise (PEM) or orthostatic intolerance (OI). Nevertheless, PEM and OI are not routinely assessed by clinicians. We estimated PEM and OI proportions in PL-PCC, as well in people not living with PCC (PnL-PCC) and negatives (i.e., never reported a SARS-CoV-2 positive test), and identified associated factors. Methods Participants from the PRIME post-COVID study were included. PEM and OI were assessed using validated questionnaires. PCC was defined as feeling unrecovered after SARS-CoV-2 infection. Multivariable regression analyses to study PEM and OI were stratified for sex. Results Data from 3,783 participants was analyzed. In PL-PCC, proportion of PEM was 48.1% and 41.2%, and proportion of OI was 29.3% and 27.9% in women and in men, respectively. Proportions were higher in PL-PCC compared to negatives, for PEM in women OR=4.38 [95%CI:3.01-6.38]; in men OR=4.78 [95%CI:3.13-7.29]; for OI in women 3.06 [95%CI:1.97-4.76]; in men 2.71 [95%CI:1.75-4.21]. Associated factors were age [≤]60 years, [≥]1 comorbidities and living alone. Conclusions High proportions of PEM and OI are observed in PL-PCC. Standard screening for PEM and OI is recommended in PL-PCC, to promote appropriate therapies. Trial registration ClinicalTrials.gov identifier:NCT05128695


Subject(s)
COVID-19 , Orthostatic Intolerance
3.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3112133.v1

ABSTRACT

Covid-19 outbreak has drawn attention to the fact that viral infections might present with clinical bradycardia. Seeking its clinical significance, not yet unveiled by the literature, we come across other viral infections that also show clinical bradycardia during its clinical course, such as dengue fever and viral diarrhea. The clinical presentation of the latest seems to be severe, often presenting with orthostatic intolerance and fatigue symptoms, requiring expert consultation irrespective of the infection stage, and in case of dengue fever, frequently during the recovery phase. Meanwhile, in Covid-19 infected patients, the bradycardia observed is mild, frugal, and usually asymptomatic. Thus, we conducted a comparison between two different groups of patients with viral infection displaying clinical bradycardia during hospital stay: Covid and non-Covid patients regarding clinical and Holter monitoring parameters. All patients had other causes of bradycardia excluded and echocardiography and cardiac biomarkers ruled out acute myocarditis. The results showed that non-Covid patients presented with significantly lower mean and minimum heart rates (HR) on Holter monitoring, as well as longer times in with HR < 50 beats per minute (bpm).  SDNN and pNN>50% were also significantly higher in non-Covid patients. The minimum systolic BP was significantly lower in non-Covid patients. The study shows that Covid-19 is not the only viral infection that may display with clinical bradycardia, but it’s much milder than other viral infections such as dengue fever and viral diarrhea. It remains unclear the mechanism throughout Covid-related bradycardia comes about.


Subject(s)
Orthostatic Intolerance , Dengue , Infections , Fatigue Syndrome, Chronic , Myocarditis , Virus Diseases , COVID-19 , Bradycardia , Heart Diseases , Diarrhea
4.
Int J Environ Res Public Health ; 20(10)2023 05 12.
Article in English | MEDLINE | ID: covidwho-20237187

ABSTRACT

INTRODUCTION: A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS. METHODS: NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman's rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score. RESULTS: Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor). CONCLUSIONS: We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency.


Subject(s)
COVID-19 , Hypotension, Orthostatic , Orthostatic Intolerance , Postural Orthostatic Tachycardia Syndrome , Humans , Orthostatic Intolerance/diagnosis , Retrospective Studies , Post-Acute COVID-19 Syndrome , Dizziness/etiology , COVID-19/diagnosis , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/epidemiology , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/epidemiology
5.
Arq Neuropsiquiatr ; 81(2): 146-154, 2023 02.
Article in English | MEDLINE | ID: covidwho-2255782

ABSTRACT

BACKGROUND: The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. OBJECTIVE: To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. METHODS: Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. RESULTS: The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). CONCLUSION: A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.


ANTECEDENTES: As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. OBJETIVO: Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. MéTODOS: Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. RESULTADOS: A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91% dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). CONCLUSãO: Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.


Subject(s)
Ageusia , COVID-19 , Hypertension , Orthostatic Intolerance , Xerophthalmia , Humans , Male , Adult , Middle Aged , Aged , Female , COVID-19/complications , Anosmia/epidemiology , SARS-CoV-2 , Dizziness/epidemiology , Quality of Life , Brazil/epidemiology , Comorbidity , Hypertension/epidemiology
6.
Auton Neurosci ; 245: 103071, 2023 03.
Article in English | MEDLINE | ID: covidwho-2231377

ABSTRACT

Patients with long COVID suffer from many neurological manifestations that persist for 3 months following infection by SARS-CoV-2. Autonomic dysfunction (AD) or dysautonomia is one complication of long COVID that causes patients to experience fatigue, dizziness, syncope, dyspnea, orthostatic intolerance, nausea, vomiting, and heart palpitations. The pathophysiology behind AD onset post-COVID is largely unknown. As such, this review aims to highlight the potential mechanisms by which AD occurs in patients with long COVID. The first proposed mechanism includes the direct invasion of the hypothalamus or the medulla by SARS-CoV-2. Entry to these autonomic centers may occur through the neuronal or hematogenous routes. However, evidence so far indicates that neurological manifestations such as AD are caused indirectly. Another mechanism is autoimmunity whereby autoantibodies against different receptors and glycoproteins expressed on cellular membranes are produced. Additionally, persistent inflammation and hypoxia can work separately or together to promote sympathetic overactivation in a bidirectional interaction. Renin-angiotensin system imbalance can also drive AD in long COVID through the downregulation of relevant receptors and formation of autoantibodies. Understanding the pathophysiology of AD post-COVID-19 may help provide early diagnosis and better therapy for patients.


Subject(s)
Autonomic Nervous System Diseases , COVID-19 , Orthostatic Intolerance , Humans , COVID-19/complications , Post-Acute COVID-19 Syndrome , SARS-CoV-2 , Autonomic Nervous System Diseases/etiology
7.
Medicina (Kaunas) ; 58(12)2022 Dec 08.
Article in English | MEDLINE | ID: covidwho-2155201

ABSTRACT

Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection. The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID. We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels. We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability), also affects the vasa vasorum to impair the function of the capacitance vessels. In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.


Subject(s)
Autonomic Nervous System Diseases , COVID-19 , Fatigue Syndrome, Chronic , Orthostatic Intolerance , Humans , Orthostatic Intolerance/complications , Orthostatic Intolerance/diagnosis , Vasa Vasorum , Microcirculation , Post-Acute COVID-19 Syndrome , COVID-19/complications
8.
Auton Neurosci ; 241: 102997, 2022 09.
Article in English | MEDLINE | ID: covidwho-1889237

ABSTRACT

The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.


Subject(s)
COVID-19 , Hypotension, Orthostatic , Orthostatic Intolerance , Postural Orthostatic Tachycardia Syndrome , Blood Pressure , COVID-19/complications , Heart Rate , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/etiology , Orthostatic Intolerance/diagnosis , Postural Orthostatic Tachycardia Syndrome/complications , Postural Orthostatic Tachycardia Syndrome/diagnosis , Retrospective Studies , Tilt-Table Test , Post-Acute COVID-19 Syndrome
9.
Neurol Sci ; 43(8): 4635-4643, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1859006

ABSTRACT

INTRODUCTION: Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection. OBJECTIVE: The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients. METHODS: In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID - group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses. RESULTS: The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31. CONCLUSION: Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.


Subject(s)
Autonomic Nervous System Diseases , COVID-19 , Orthostatic Intolerance , Autonomic Nervous System Diseases/diagnosis , COVID-19/complications , Cross-Sectional Studies , Humans , SARS-CoV-2
10.
Ann Clin Transl Neurol ; 9(6): 778-785, 2022 06.
Article in English | MEDLINE | ID: covidwho-1782552

ABSTRACT

BACKGROUND: The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking. OBJECTIVE: To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome. METHODS: We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19. RESULTS: We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001). CONCLUSIONS: Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.


Subject(s)
COVID-19 , Orthostatic Intolerance , Primary Dysautonomias , COVID-19/complications , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Primary Dysautonomias/epidemiology , Primary Dysautonomias/etiology , Syndrome , Post-Acute COVID-19 Syndrome
11.
J Am Coll Cardiol ; 79(23): 2325-2330, 2022 06 14.
Article in English | MEDLINE | ID: covidwho-1768221

ABSTRACT

BACKGROUND: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed. OBJECTIVES: This study performed head-up tilt table (HUTT) testing in symptomatic patients with PASC to evaluate for orthostatic intolerance suggestive of autonomic dysfunction. METHODS: We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT. RESULTS: Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and 1 orthostatic hypotension. Compared with those with POTS, patients with POI described significantly earlier improvement of symptoms. CONCLUSIONS: This prospective evaluation of HUTT in patients with PASC revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.


Subject(s)
COVID-19 , Orthostatic Intolerance , Postural Orthostatic Tachycardia Syndrome , COVID-19/complications , Heart Rate , Humans , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/etiology , Postural Orthostatic Tachycardia Syndrome/diagnosis , Tilt-Table Test
12.
J Neurovirol ; 28(1): 158-161, 2022 02.
Article in English | MEDLINE | ID: covidwho-1709619

ABSTRACT

Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.


Subject(s)
COVID-19 , Orthostatic Intolerance , Postural Orthostatic Tachycardia Syndrome , COVID-19/complications , Disease Progression , Fatigue/complications , Humans , Orthostatic Intolerance/complications , Orthostatic Intolerance/diagnosis , Postural Orthostatic Tachycardia Syndrome/complications , Postural Orthostatic Tachycardia Syndrome/diagnosis , SARS-CoV-2
13.
Ann Neurol ; 91(3): 367-379, 2022 03.
Article in English | MEDLINE | ID: covidwho-1636023

ABSTRACT

OBJECTIVE: The purpose of this study was to describe cerebrovascular, neuropathic, and autonomic features of post-acute sequelae of coronavirus disease 2019 ((COVID-19) PASC). METHODS: This retrospective study evaluated consecutive patients with chronic fatigue, brain fog, and orthostatic intolerance consistent with PASC. Controls included patients with postural tachycardia syndrome (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor, and tilt tests), cerebrovascular (cerebral blood flow velocity [CBFv] monitoring in middle cerebral artery), respiratory (capnography monitoring), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers. RESULTS: Nine patients with PASC were evaluated 0.8 ± 0.3 years after a mild COVID-19 infection, and were treated as home observations. Autonomic, pain, brain fog, fatigue, and dyspnea surveys were abnormal in PASC and POTS (n = 10), compared with controls (n = 15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0 ± 13.4%) and POTS (-20.3 ± 15.1%), compared with controls (-3.0 ± 7.5%, p = 0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n = 6) and with (n = 3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p = 0.002). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs 60%) but not in inflammatory markers (67% vs 70%). Supine and orthostatic hypocapnia was observed in PASC. INTERPRETATION: PASC following mild COVID-19 infection is associated with multisystem involvement including: (1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; (2) small fiber neuropathy and related dysautonomia; (3) respiratory dysregulation; and (4) chronic inflammation. ANN NEUROL 2022;91:367-379.


Subject(s)
Blood Pressure/physiology , COVID-19/complications , Cerebrovascular Circulation/physiology , Heart Rate/physiology , Inflammation Mediators/blood , Adult , COVID-19/blood , COVID-19/diagnosis , COVID-19/physiopathology , Fatigue/blood , Fatigue/diagnosis , Fatigue/physiopathology , Female , Humans , Male , Middle Aged , Orthostatic Intolerance/blood , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/physiopathology , Retrospective Studies , Post-Acute COVID-19 Syndrome
14.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.24.21268370

ABSTRACT

Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e. self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. To accomplish such an investigation, a wide range of continuous non-invasive biomedical technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. With the novel technique described and exemplified in this paper, we were able to integrate signals from all instruments used in the assessment in a precisely synchronized fashion. We demonstrate that it is possible to visualize the interactions between all different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. The proposed multimodal data visualization can offer an overview of the functioning of the muscle pump during both supine rest and orthostatic recovery and can conduct comparison studies with signals from multiple participants at any given time in the assessment. This could help researchers and clinicians generate and test hypotheses based on the multimodal inspection of raw data, in long COVID and other clinical cohorts.


Subject(s)
Neuromuscular Diseases , Tremor , Nervous System Diseases , Fatigue , Orthostatic Intolerance , Chromosomal Instability
15.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.19.21268060

ABSTRACT

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults with long COVID. Participants underwent a 3-minute active stand (AS) with Finapres® NOVA, followed by a 10-minute unmedicated 70-degree head-up tilt test. 85 participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OI AS ). OI AS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the 1 st minute post-stand (mean HR nadir 88 vs 75 bpm, P=0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HR nadir was the only OI AS predictor (OR=1.09, 95% CI: 1.01-1.18, P=0.027). 22 participants had initial (iOH) and 5 classical (cOH) orthostatic hypotension, but neither correlated with OI AS . 71 participants proceeded to tilt, of which 28 had OI during tilt (OI tilt ). Of the 53 who had a 10-minute tilt, 7 (13%) fulfilled hemodynamic postural orthostatic tachycardia syndrome (POTS) criteria, but 6 did not report OI tilt . OI AS was associated with a higher initial HR on AS, which after 1 minute equalized with the non-OI AS group. Despite these initial orthostatic HR differences, POTS was infrequent and largely asymptomatic. ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).


Subject(s)
Postural Orthostatic Tachycardia Syndrome , Orthostatic Intolerance
16.
J Am Geriatr Soc ; 69(3): 767-772, 2021 03.
Article in English | MEDLINE | ID: covidwho-975561

ABSTRACT

BACKGROUND: Exacerbation of or new onset orthostatic hypotension in perioperative patients can occur. There is complex underlying pathophysiology with further derailment likely caused by acute cardiovascular changes associated with surgery. The implications for post-operative recovery are unclear, particularly in frail and older patients. We retrospectively explored patient notes for evidence of post-operative orthostatic intolerance in relation to pre-operative orthostatic hypotension. METHODS: Supine and 1-minute and 3-minute standing blood pressure measures obtained from adult patients before mainly general, orthopedic or uro/gynecology surgery were compared to post-operative outcome, specifically, evidence in patient notes about falls, feeling dizzy/unsteady and/or fearful to stand. Orthostatic hypotension was defined as a 20 mmHg or more and/or 10 mmHg or more fall in systolic and diastolic blood pressure, respectively, within ~3 minutes of standing after lying supine for an electrocardiogram. RESULTS: Whilst all patients included had a 1-minute standing blood pressure assessment (N = 170), 3-minute assessment was performed less commonly (N = 113). Nevertheless, one-quarter (23.5%; N = 40) of 170 patients had pre-operative orthostatic hypotension. This was not clearly explained by cardiac or neurological disease or by common medications, but did occur more frequently in older patients and in those aged 65 years or more with higher clinical frailty scale scores. The COVID-19 pandemic reduced the number of patients progressing to surgery within the planned study timescale (N = 143/170; 84.1%). Nevertheless, patients with orthostatic hypotension stayed longer in hospital post-operatively and were more likely to have an episode of fall, unsteadiness and/or dizziness documented (un-prompted) in their notes. CONCLUSIONS: These data provide further impetus for research into modifiable perioperative risk factors associated with orthostatic hypotension. These risks are not confined to those with a pre-existing dysautonomia diagnosis.


Subject(s)
Blood Pressure , Frailty/physiopathology , Hypotension, Orthostatic/diagnosis , Orthostatic Intolerance/etiology , Postoperative Complications/etiology , Aged , Aged, 80 and over , Blood Pressure Determination , COVID-19 , Female , Frailty/complications , Frailty/surgery , Geriatric Assessment , Humans , Hypotension, Orthostatic/etiology , Male , Preoperative Period , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome
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