COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective

Abstract:

Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs. Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help. Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenals, and thyroid.

Source: Bansal R, Gubbi S, Koch CA. COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective. J Clin Transl Endocrinol. 2021 Dec 3:100284. doi: 10.1016/j.jcte.2021.100284. Epub ahead of print. PMID: 34877261; PMCID: PMC8641402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641402/ (Full text)

Chronic fatigue syndrome against the background of the COVID-19 pandemic

Abstract:

The more we learn about the new coronavirus infection, the more we understand that we will feel the echoes of the pandemic for many years, and those who have successfully endured the acute phase of COVID-19 may face the consequences of the infection. One of the most frequent manifestations will be the development of chronic fatigue syndrome (CFS) after COVID-19. This article discusses the possible causes of the development of CFS, as well as possible ways of its treatment and prevention.

Source: Nikitina AJ, Levin OS. Sindrom khronicheskoi ustalosti na fone pandemii COVID-19 [Chronic fatigue syndrome against the background of the COVID-19 pandemic]. Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(10. Vyp. 2):92-98. Russian. doi: 10.17116/jnevro202112110292. PMID: 34870921. https://pubmed.ncbi.nlm.nih.gov/34870921/  [in English, Russian]

Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection

Abstract:

Clinical features of Coronavirus disease 2019 (COVID-19) are caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial healthcare issue, and the development of long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as impaired capillary microcirculation, chronic fatigue syndrome (CFS), proinflammatory cytokines, and functional autoantibodies targeting G-protein-coupled receptors (GPCR-AAbs). Here, we present a case report of successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with a high affinity to GPCR-AAbs that neutralizes these AAbs.

A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from CFS, loss of taste, and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by constant improvement of the fatigue symptoms of the patient, taste, and retinal capillary microcirculation. Therefore, the removal of GPCR-AAb might ameliorate the characteristics of the LCD, such as capillary impairment, loss of taste, and CFS.

Source: Hohberger B, Harrer T, Mardin C, Kruse F, Hoffmanns J, Rogge L, Heltmann F, Moritz M, Szewczykowski C, Schottenhamml J, Kräter M, Bergua A, Zenkel M, Gießl A, Schlötzer-Schrehardt U, Lämmer R, Herrmann M, Haberland A, Göttel P, Müller J, Wallukat G. Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection. Front Med (Lausanne). 2021 Nov 18;8:754667. doi: 10.3389/fmed.2021.754667. PMID: 34869451; PMCID: PMC8637609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637609/ (Full text)

Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome

Abstract:

In this paper we highlight the presence of tachycardia in post-acute COVID-19 syndrome by introducing a new label for this phenomenon—post-COVID-19 tachycardia syndrome—and argue that this constitutes a phenotype or sub-syndrome in post-acute COVID-19 syndrome. We also discuss epidemiology, putative mechanisms, treatment options, and future research directions in this novel clinical syndrome.

Source: Ståhlberg M, Reistam U, Fedorowski A, et al. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome [published online ahead of print, 2021 Aug 11]. Am J Med. 2021;S0002-9343(21)00472-1. doi:10.1016/j.amjmed.2021.07.004  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356730/ (Full text)

Covid and ME/CFS

Announcement:

AMMES has recently added an informational page about COVID-19 and ME/CFS. The page includes physicians’ recommendations regarding the COVID vaccine for people with ME/CFS, patient surveys on how the vaccine has affected them, research articles on long-Covid and ME/CFS, related news items, and tips from doctors on how to treat patients with ME/CFS who contract COVID-19. You can find the page here:  https://ammes.org/covid-19/

Mistaken Identity: Many Diagnoses are Frequently Misattributed to Lyme Disease

Abstract:

Background: Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

Methods: This retrospective observational cohort study evaluated patients referred for Lyme disease to a Mid-Atlantic academic center between 2000-2013 who lacked evidence for Borrelia burgdorferi infection. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Results: Of 1261 referred patients, 1061 (84%) had no findings of active Lyme disease, with 690 (65%) receiving other diagnoses resulting in 405 (59%) having newly diagnosed medical conditions, 134 (19%) attributed to pre-existing medical issues, and 151 (22%) had both new and pre-existing conditions. Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%. Leading diagnoses were anxiety/depression 222 (21%), fibromyalgia 120 (11%), chronic fatigue syndrome 77 (7%), migraine disorder 74 (7%), osteoarthritis 62 (6%) and sleep disorder/apnea 48 (5%). Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis (11), malignancy (8), Parkinson’s disease (8), sarcoidosis (4) or amyotrophic lateral sclerosis (4).

Conclusions: Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

Source: Kobayashi T, Higgins Y, Melia MT, Auwaerter PG. Mistaken Identity: Many Diagnoses are Frequently Misattributed to Lyme Disease. Am J Med. 2021 Nov 30:S0002-9343(21)00792-0. doi: 10.1016/j.amjmed.2021.10.040. Epub ahead of print. PMID: 34861197. https://www.sciencedirect.com/science/article/pii/S0002934321007920  (Full text)

Persistent Exertional Intolerance After COVID-19

Abstract:

Background: Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by conventional investigative studies.

Research question: What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome after COVID-19 in patients without cardiopulmonary disease?

Study design and methods: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19.

Results: The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation.

Interpretation: Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.

Source: Singh I, Joseph P, Heerdt PM, Cullinan M, Lutchmansingh DD, Gulati M, Possick JD, Systrom DM, Waxman AB. Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. Chest. 2021 Aug 11:S0012-3692(21)03635-7. doi: 10.1016/j.chest.2021.08.010. Epub ahead of print. PMID: 34389297; PMCID: PMC8354807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354807/  (Full text)

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease

Abstract:

Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Conclusions: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

Source: Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease. JACC Heart Fail. 2021 Dec;9(12):927-937. doi: 10.1016/j.jchf.2021.10.002. PMID: 34857177.  https://pubmed.ncbi.nlm.nih.gov/34857177/

Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19

Abstract:

Background and methods: Skeletal muscle-related symptoms are common in both acute Covid-19 and Post-Acute Sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected, and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy and post-viral fatigue syndrome.
Results: Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fiber atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxemia, and malnutrition. These factors also contribute to post-ICU syndrome and ICU-acquired weakness, and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure and different factors likely contribute. Direct SARS-CoV-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study.
Conclusion: Both SARS-CoV-2 specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid 19 and PASC.
Source: Soares, M., Eggelbusch, M., Naddaf, E., Gerrits, K., van der Schaaf, M., van den Borst, B., Wiersinga, W. J., et al. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. Journal of Cachexia, Sarcopenia and Muscle. https://doi.org/10.17863/CAM.78509 https://www.repository.cam.ac.uk/handle/1810/331064

Intestinal flora and neurological disorders

Abstract:

The human intestinal flora is a highly diverse ecosystem composed of trillions of bacteria. The imbalance of the flora is related to a variety of diseases. The intestinal flora interacts with the nervous system bidirectionally in many ways through the gut-brain axis. It causes neuroimmune inflammatory response, dysfunction of gut mucosa and blood-brain barrier, direct stimulation of the vagus nerve, spinal nerve of the enteric nervous system, and the neuroendocrine hypothalamus-pituitary-adrenal axis, causing neurological disorders. The metabolites of the intestinal microbial community also play a role.

This article summarizes the characteristics of the altered intestinal flora and intervention measures in autism spectrum disorder, multiple sclerosis, Parkinson’s disease, epilepsy, Guillain-Barré syndrome, Alzheimer’s disease, neuromyelitis optica, hepatic encephalopathy, amyotrophic lateral sclerosis, schizophrenia, depression, chronic fatigue syndrome, Huntington’s disease and stroke. The current research on intestinal flora is still in its infancy, and very few studies were carried out on causality and the underlying mechanisms, which prevents the development of precise flora-based clinical intervention measures. It is expected the research on intestinal flora would lead to novel approaches for treatment of some neurological disorders.

Source: Tang Q, Cao L. [Intestinal flora and neurological disorders]. Sheng Wu Gong Cheng Xue Bao. 2021 Nov 25;37(11):3757-3780. Chinese. doi: 10.13345/j.cjb.210253. PMID: 34841782. https://pubmed.ncbi.nlm.nih.gov/34841782/