Exaggerated blood pressure elevation in response to orthostatic challenge, a post-acute sequelae of SARS-CoV-2 infection (PASC) after hospitalization

Abstract:

Objective: Post-acute sequelae of SARS-COV-2 (PASC) are emerging as a major health challenge. Orthostatic intolerance secondary to autonomic failure has been found in PASC patients. This study investigated the effect of COVID-19 after recovery on blood pressure (BP) during the orthostatic challenge.

Research design and methods: Thirty-one out of 45 patients hospitalized due to COVID-19-related pneumonia that developed PASC and did not have hypertension at discharge were studied. They underwent a head-up tilt test (HUTT) at 10.8 ± 1.9 months from discharge. All met the PASC clinical criteria, and an alternative diagnosis did not explain the symptoms. This population was compared with 32 historical asymptomatic healthy controls.

Results: Exaggerated orthostatic blood pressure response (EOPR)/orthostatic hypertension (OHT) was detected in 8 out of 23 (34.7 %) patients, representing a significantly increased prevalence (7.67-fold increase p = 0.009) compared to 2 out of 32 (6.4 %) asymptomatic healthy controls matched by age, who underwent HUTT and were not infected with SARS-CoV-2.

Conclusions: This prospective evaluation in patients with PASC revealed abnormal blood pressure rise during the orthostatic challenge, suggesting of autonomic dysfunction in a third of the studied subjects. Our findings support the hypothesis that EOPR/OHT may be a phenotype of neurogenic hypertension. Hypertension in PASC patients may adversely affect the cardiovascular burden in the world.

Source: González-Hermosillo G JA, Galarza EJ, Fermín OV, González JMN, Tostado LMFÁ, Lozano MAE, Rabasa CR, Martínez Alvarado MDR. Exaggerated blood pressure elevation in response to orthostatic challenge, a post-acute sequelae of SARS-CoV-2 infection (PASC) after hospitalization. Auton Neurosci. 2023 Apr 21;247:103094. doi: 10.1016/j.autneu.2023.103094. Epub ahead of print. PMID: 37137186; PMCID: PMC10121145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121145/ (Full text)

Autonomic Dysfunction related to Post-Acute SARS-CoV-2 Syndrome

Introduction:

The SARS-CoV-2 virus, a member of the coronavirus family, has been responsible for the Coronavirus Disease-19 (COVID-19) pandemic with an acute phase causing pneumonia and pulmonary disorders, but it has been shown to extrapulmonary manifestations including cardiovascular and neurological diseases. Moreover, residual symptoms have been reported to persist past the acute phase. In a cross-sectional study of SARS-CoV-2 positive patients, at 48 days post-discharge the most common persistent symptoms were fatigue, difficulty breathing, and psychological distress.
 In a cohort study of 1,733 COVID-19 patients from Wuhan, China, patients reported persistence of fatigue, muscle weakness, sleeping difficulties, palpitations, anxiety, or depression at 6 months after initial onset.
 Numerous other studies now indicate the presence of persistent symptoms following COVID-19 infection, with over 200 symptoms reported. This syndrome has been coined as the Post-Acute SARS-CoV-2 Syndrome (PASC) and has been defined as the persistence of symptoms or development of new symptoms after the time of infection, which can include fatigue, brain fog, palpitations, and a plethora of other manifestations.
Source: Justin Haloot, DO, MS, MS, Ratna Bhavaraju-Sanka, MD, Jayasree Pillarisetti, MD Msc, Monica Verduzco-Gutierrez, MD. Autonomic Dysfunction related to Post-Acute SARS-CoV-2 Syndrome. Physical Medicine and Rehabiliation Clinics. Published: April 18, 2023. DOI:https://doi.org/10.1016/j.pmr.2023.04.003 (Full text)

Exercise Intolerance Associated with Impaired Oxygen Extraction in Patients with Long COVID

Abstract:

Objective: Chronic mental and physical fatigue and post-exertional malaise are the more debilitating symptoms of long COVID-19. The study objective was to explore factors contributing to exercise intolerance in long COVID-19 to guide development of new therapies. Exercise capacity data of patients referred for a cardiopulmonary exercise test (CPET) and included in a COVID-19 Survivorship Registry at one urban health center were retrospectively analyzed.

Results: Most subjects did not meet normative criteria for a maximal test, consistent with suboptimal effort and early exercise termination. Mean O2 pulse peak % predicted (of 79 ± 12.9) was reduced, supporting impaired energy metabolism as a mechanism of exercise intolerance in long COVID, n=59. We further identified blunted rise in heart rate peak during maximal CPET. Our preliminary analyses support therapies that optimize bioenergetics and improve oxygen utilization for treating long COVID-19.

Source: Norweg A, Yao L, Barbuto S, Nordvig AS, Tarpey T, Collins E, Whiteson J, Sweeney G, Haas F, Leddy J. Exercise Intolerance Associated with Impaired Oxygen Extraction in Patients with Long COVID. Respir Physiol Neurobiol. 2023 Apr 17;313:104062. doi: 10.1016/j.resp.2023.104062. Epub ahead of print. PMID: 37076024; PMCID: PMC10108551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108551/ (Full text)

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan

Abstract:

Purpose: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters.

Methods: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal–Wallis test. Multiple comparison tests were performed using the Dunn’s test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals.

Results: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively.

Conclusions: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

Source: Tsuchida, T., Yoshimura, N., Ishizuka, K. et al. Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan. Clin Exp Med (2023). https://doi.org/10.1007/s10238-023-01057-6 (Full text)

Cardiovascular Considerations in the Management of People with Suspected Long COVID

Abstract:

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks post-acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection may present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat.

When assessing patients with these symptoms, clinicians need to keep in mind Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), post-exertional malaise and post-exertional symptom exacerbation (PEM/PESE), cardiac dysautonomia such as Inappropriate Sinus Tachycardia (IST), and Postural Orthostatic Tachycardia Syndrome (POTS), and occasionally Mast Cell Activation Syndrome (MCAS).

This paper summarizes the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, this review includes a Canadian perspective, consisting of a panel of expert opinions from experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.

Source: Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. https://www.onlinecjc.ca/article/S0828-282X(23)00303-3/fulltext (Full text)

Heart Rate Variability and Salivary Biomarkers Differences between Fibromyalgia and Healthy Participants after an Exercise Fatigue Protocol: An Experimental Study

Abstract:

Previous studies showed that people with Fibromyalgia (FM) suffer from dysautonomia. Dysautonomia consists of persistent autonomic nervous system hyperactivity at rest and hyporeactivity during stressful situations. There is evidence that parameters reflecting the complex interplay between the autonomic nervous system and the cardiovascular system during exercise can provide significant prognostic information. Therefore, this study aimed to investigate the differences between people with FM and healthy controls on heart rate variability (HRV) and salivary parameters (such as flow, protein concentration, enzymatic activities of amylase, catalase and glutathione peroxidase) in two moments: (1) at baseline, and (2) after an exercise fatigue protocol.

A total of 37 participants, twenty-one were people with fibromyalgia and sixteen were healthy controls, participated in this cross-sectional study. HRV and salivary samples were collected before and after an exercise fatigue protocol. The fatigue protocol consisted of 20 repetitions of knee extensions and flexions of the dominant leg at 180 °·s-1 (degrees per second).

Significant differences were found in the HRV (stress index, LF and HF variables) and salivary biomarkers (with a higher concentration of salivary amylase in people with FM compared to healthy controls). Exercise acute effects on HRV showed that people with FM did not significantly react to exercise. However, significant differences between baseline and post-exercise on HRV significantly induce alteration on the HRV of healthy controls. Catalase significantly increased after exercise in healthy controls whereas salivary flow significantly increased in women with FM after an exercise fatigue protocol.

Our study suggests that a higher α-amylase activity and an impaired HRV can be used as possible biomarkers of fibromyalgia, associated with a reduction in salivary flow without changes in HRV and catalase activity after a fatigue exercise protocol. More studies should be carried out in the future to evaluate this hypothesis, in order to find diagnostic biomarkers in fibromyalgia.

Source: Costa AR, Freire A, Parraca JA, Silva V, Tomas-Carus P, Villafaina S. Heart Rate Variability and Salivary Biomarkers Differences between Fibromyalgia and Healthy Participants after an Exercise Fatigue Protocol: An Experimental Study. Diagnostics (Basel). 2022 Sep 14;12(9):2220. doi: 10.3390/diagnostics12092220. PMID: 36140620; PMCID: PMC9497903. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497903/ (Full text)

Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy

Abstract:

Postural Orthostatic Tachycardia Syndrome (POTS) is a rare disorder of the autonomic nervous system. The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed.

This case report is about a patient with post-viral neuropathic POTS.

Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia.

Current literature emphasizes a treatment that is based on lifestyle modifications, such as increasing water and salt intake, and symptomatic pharmacological treatment.

In this case, the 39-year-old male patient was treated with osteopathic manipulative treatment (OMT), specifically the compression of the fourth ventricle (CV4), which has been associated with the production of hyperparasympathetic and anti-inflammatory effects and, hence, helps overcome the small-fiber neuropathy caused by the viral illness.

We found that the CV4 technique led to the successful remission of the patient’s symptoms. Therefore, we propose craniosacral therapy as a successful single management modality in patients with POTS.

Source: Tafler L, Chaudry A, Cho H, Garcia A. Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy. Cureus. 2023 Feb 15;15(2):e35009. doi: 10.7759/cureus.35009. PMID: 36938206; PMCID: PMC10021347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021347/ (Full text)

Autoimmunity in Long Covid and POTS

Abstract:

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalised immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but prevalence with its supporting evidence is compelling.

In this review, we discuss the role of the autonomic nervous and immune systems in Covid and Long Covid and their potential influence on symptoms and clinical practice. Additionally, overlap with non-Covid autonomic dysfunction is considered. Understanding these new disorders can inform both neuro-immunology and Long Covid management.

Source: Fatema-Zahra El-Rhermoul, Artur Fedorowski, Philip Eardley, Patricia Taraborrelli, Dimitrios Panagopoulos, Richard Sutton, Phang Boon Lim, Melanie Dani, Autoimmunity in Long Covid and POTS, Oxford Open Immunology, 2023;, iqad002, https://doi.org/10.1093/oxfimm/iqad002 (Full text available as PDF file)

Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID

Abstract:

Background: Dysautonomia seems to be important for the pathophysiology of psychosomatic diseases and, more recently, for long COVID. This concept may explain the clinical symptoms and could help open new therapeutic approaches.
Methods: We compared our data from an analysis of heart rate variability (HRV) in an active standing test in 28 adolescents who had developed an inappropriate sinus tachycardia (IST, n = 13) or postural orthostatic tachycardia syndrome (POTS, n = 15) after contracting COVID-19 disease and/or vaccination with 64 adolescents from our database who developed dysautonomia due to psychosomatic diseases prior to the COVID-19 pandemic. We prove the effects of our treatment: omega-3 fatty acid supplementation (O3-FA, n = 18) in addition to propranolol (low dose, up to 20-20-0 mg, n = 32) or ivabradine 5-5-0 mg (n = 17) on heart rate regulation and heart rate variability (HRV).
Results: The HRV data were not different between the adolescents with SARS-CoV-2-related disorders and the adolescents with dysautonomia prior to the pandemic. The heart rate increases in children with POTS while standing were significantly lower after low-dose propranolol (27.2 ± 17.4 bpm***), ivabradine (23.6 ± 8.12 bpm*), and O-3-FA (25.6 ± 8.4 bpm*). The heart rate in children with IST while lying/standing was significantly lower after propranolol (81.6 ± 10.1 bpm**/101.8 ± 18.8***), ivabradine (84.2 ± 8.4 bpm***/105.4 ± 14.6**), and O-3-FA (88.6 ± 7.9 bpm*/112.1/14.9*).
Conclusions: The HRV data of adolescents with dysautonomia after COVID-19 disease/vaccination are not significantly different from a historical control of adolescents with dysautonomia due to psychosomatic diseases prior to the pandemic. Low-dose propranolol > ivabradine > omega-3 fatty acids significantly decrease elevated heart rates in patients with IST and the heart rate increases in patients with POTS and may be beneficial in these children with dysautonomia.
Source: Buchhorn R. Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID. Children. 2023; 10(2):316. https://doi.org/10.3390/children10020316 https://www.mdpi.com/2227-9067/10/2/316 (Full text)

Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome

Abstract:

The post-acute sequelae of COVID-19 present major problems for many patients, their physicians and the health-care system. They are unrelated to the severity of the initial infection, are often highly symptomatic and can occur after vaccination. Many sequelae involve cardiovascular autonomic dysfunction, with postural orthostatic tachycardia syndrome in 30% of individuals. Prognosis is unknown, and treatment is still unsatisfactory.

Source: Fedorowski A, Sutton R. Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome. Nat Rev Cardiol. 2023 Feb 2:1–2. doi: 10.1038/s41569-023-00842-w. Epub ahead of print. PMID: 36732397; PMCID: PMC9893964. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893964/ (Full text)