Tag: 2023

Long COVID: a review and proposed visualization of the complexity of long COVID

Abstract:

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and public health officials to guide the global effort toward an improved understanding of Long COVID and the eventual mechanism-based provision of care to afflicted patients. The proposed visualization or framework for Long COVID should be an evidence-based, dynamic, modular, and systems-level approach to the condition.

Furthermore, with further research such a framework could establish the strength of the relationships between pre-existing conditions (or risk factors), biological mechanisms, and resulting clinical phenotypes and outcomes of Long COVID. Notwithstanding the significant contribution that disparities in access to care and social determinants of health have on outcomes and disease course of long COVID, our model focuses primarily on biological mechanisms. Accordingly, the proposed visualization sets out to guide scientific, clinical, and public health efforts to better understand and abrogate the health burden imposed by long COVID.

Source: Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D, Garzino-Demo A, Brechot C, Parthasarathy S, Vahlne A, Nikolich JŽ. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol. 2023 Apr 20;14:1117464. doi: 10.3389/fimmu.2023.1117464. PMID: 37153597; PMCID: PMC10157068. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157068/ (Full text)

Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation

Abstract:

Abstract available online: https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

Source: S. Jothi, G. Claessen, M. Insel, S. Kubba, E. Howden, S.-R. Carmona, F.P. Rischard. Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

ME/CFS Pathophysiology Investigated by Invasive Cardiopulmonary Exercise Testing and Autonomic Function Testing

Abstract

Introduction: Mechanisms underlying exercise and orthostatic intolerance in myalgic encephalomyelitis/chronic
fatigue syndrome (ME/CFS) have been uncovered by invasive cardiopulmonary exercise testing (iCPET) and
autonomic function testing (AFT), but the relationships between the two are not known. This study aims to determine
if there is overlap of cardiovascular and respiratory pathophysiology in patients who have undergone both
tests.

Methods: Between January 2017 and April 2022, 62 patients were identified with a contemporary iCPET and
AFT. Key variables from the iCPET included peak oxygen uptake (pVO2), cardiac output (pQc), right atrial pressure
(pRAP), and systemic oxygen extraction (Ca-vOy/Hgb) at peak exercise. Key variables from the autonomic testing
included epidermal and sweat gland small fiber neurite density, electrochemical skin conductance, and change in
heart rate (AH) and end tidal carbon dioxide (AETCO2) from supine to upright during the tilt table test
(TTT).

Results: All 62 patients demonstrated preload failure (pRAP < 6.5mmHg). Of this group, 54 patients (87.1%) fulfilled NAM criteria for ME/CFS, with 32 testing positive (59.3%) for small fiber neuropathy (SFN) using either morphological and/or functional testing. Significant correlations were found between pVOg and both AH (r=-0.439. P<0.05) and AETCO, (r=0.474, P<0.05) during TTT. The same tilt table variables were found to be significantly correlated with pQc (r=-0.365, P<0.05 and r=0.351, P<0.05) from the iCPET. It should be noted that 8 of the ME/CFS SFN patients (25%) fulfilled diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) based on the tilt table test.

Conclusion: Decreased oxygen uptake and cardiac output at peak exercise during iCPET correlated with a greater change in heart rate and ETCO from supine to upright during TTT. There appears to be significant overlap of cardiopulmonary pathophysiology in ME/CFS underlying exercise and orthostatic symptoms.

Source: J. Squires, K. Wichmann Madsen, M.C. Stovall, S. Al-Zayer, W. Xiao, C.-J. Chang, P. Novak, D.M. Systrom. ME/CFS Pathophysiology Investigated by Invasive Cardiopulmonary Exercise Testing and Autonomic Function Testing. American Journal of Respiratory and Critical Care Medicine 2023;207:A2996. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2996

Sex Differences in Hemodynamic Response to Exercise in Patients With Myalgic Encephalomyelitis: Insights From Invasive Cardiopulmonary Exercise Testing

Abstract:

Abstract available online: https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2995

Source: K. Wichmann Madsen, J. Squires, M.C. Stovall, S. Al-Zayer, C.-J. Chang, W. Xiao, R. Pari, P. Joseph, D.M. Systrom. Sex Differences in Hemodynamic Response to Exercise in Patients With Myalgic Encephalomyelitis: Insights From Invasive Cardiopulmonary Exercise Testing. American Journal of Respiratory and Critical Care Medicine 2023;207:A2995 https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2995

Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Highlights:

  • Adults with ME/CFS experience a 3-fold greater reduction in cerebral blood flow during end-tilt tilt compared to healthy controls, confirming orthostatic intolerance.
  • During tilt testing we found that in 134/362 (37%) patients with ME/CFS without POTS or hypotension, the heart rate increase was below the lower limit of the 95% prediction interval of the heart rate increase of controls, indicative of orthostatic chronotropic incompetence.
  • These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing, confirming another abnormality in the circulatory response to upright posture in ME/CFS.

Abstract:

Background: Orthostatic intolerance (OI) is a core diagnostic criterion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The majority of ME/CFS patients have no evidence of hypotension or postural orthostatic tachycardia syndrome (POTS) during head-up tilt, but do show a significantly larger reduction in stroke volume index (SVI) when upright compared to controls. Theoretically a reduction in SVI should be accompanied by a compensatory increase in heart rate (HR). When there is an incomplete compensatory increase in HR, this is considered chronotropic incompetence.

This study explored the relationship between HR and SVI to determine whether chronotropic incompetence was present during tilt testing in ME/CFS patients.

Methods: From a database of individuals who had undergone tilt testing with Doppler measurements for SVI both supine and end-tilt, we selected ME/CFS patients and healthy controls (HC) who had no evidence of POTS or hypotension during the test.

To determine the relation between the HR increase and SVI decrease during the tilt test in patients, we calculated the 95% prediction intervals of this relation in HC. Chronotropic incompetence in patients was defined as a HR increase below the lower limit of the 95th % prediction interval of the HR increase in HC.

Results: We compared 362 ME/CFS patients with 52 HC. At end-tilt, tilt lasting for 15 (4) min, ME/CFS patients had a significantly lower SVI (22 (4) vs. 27 (4) ml/m2; p<0.0001) and a higher HR (87 (11) vs. 78 (15) bpm; p<0.0001) compared to HC. There was a similar relationship between HR and SVI between ME/CFS patients and HC in the supine position.

During tilt ME/CFS patients had a lower HR for a given SVI; 37% had an inadequate HR increase. Chronotropic incompetence was more common in more severely affected ME/CFS patients.

Conclusion: These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing in ME/CFS patients.

Source: C. (Linda) M.C. van Campen, Freek W.A. Verheugt, Peter C. Rowe, Frans C. Visser. Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). IBRO Neuroscience Reports [In Press, Journal Pre-proof]  Available online 2 May 2023 https://www.sciencedirect.com/science/article/pii/S2667242123000374 (Full text)

Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review

Abstract:

Objectives: Fibromyalgia (FM), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other syndromes with medically unexplained symptoms (MUS) pose significant healthcare challenges. We aimed to synthesize qualitative evidence regarding the experiences of persons with these conditions (PwC) and their healthcare professionals (HCPs).

Methods & Measures: Databases were searched using terms relating to FM/ME/CFS/MUS, Experience and Qualitative research. Studies published between 2001-2021 concerning adult PwC or HCP perspectives were included and synthesized using Meta-Aggregation, with confidence established following the ConQual approach.

Results: 143 studies were included, with 708 findings aggregated into 82 categories and 13 synthesized findings. PwC narratives reflected a range of themes concerning: The experience of symptoms; The patient journey; Identity loss and change; Managing chronic illness; Understanding and legitimacy; Support needs and experiences; Healthcare needs and experiences; and Managing the healthcare encounters. HCPs perspective themes included: Beliefs and attitudes towards patients; Sensemaking at the limits of medical knowledge; Consultation and management; The patient-clinician relationship; and Barriers and facilitators to care.

Conclusion: Sensemaking challenges are at the core of the patient and clinician experience of MUS, FM and ME/CFS. While gaps in biomedical knowledge are clear, this review highlights the need to address the patient-clinician dynamic in the context of uncertainty.

Source: Duda N, Maguire R, Gitonga I, Corrigan S. Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review. PsyArXiv [Preprint], 28 Apr 2023  https://psyarxiv.com/5ct4k/ (Full text)

Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles

Abstract:

It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity.

However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID.

In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both?

Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.

Source: El-Maradny YA, Rubio-Casillas A, Uversky VN, Redwan EM. Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles. J Cell Biochem. 2023 May;124(5):656-673. doi: 10.1002/jcb.30415. Epub 2023 May 1. PMID: 37126363. https://pubmed.ncbi.nlm.nih.gov/37126363/

Netosis -A double-edged sword in the Pathogenesis of LONG COVID

Abstract:

The emergence of COVID-19 as a global pandemic has had far-reaching effects on the health of individuals worldwide. Although there has been a decrease in the severity of the disease, there is a growing concern about the long-term impact of COVID-19 on the health of individuals, particularly cardiovascular complications, known as Long-COVID, which can significantly increase morbidity and mortality rates in people recovering from COVID-19 in the recent past.
The severity of COVID-19 has been linked to various factors, including the role of neutrophils and neutrophil extracellular traps (NET). These extracellular webs, composed of chromatin, microbicidal proteins, and oxidant enzymes, are released by neutrophils to fight infections. However, if not properly regulated, NETs can lead to thrombo-inflammatory states and microangiopathy in the body, resulting in complications such as sepsis, thrombosis, and respiratory failure.
Understanding the detailed pathophysiology and association of NETs with the prognosis of COVID-19 infection is crucial for future implications and management. The purpose of this review is to analyze the potential contribution of NETosis in the pathophysiology of COVID-19 and its subsequent complications apart from its beneficial effect. This may provide insight into potential therapeutic interventions for COVID-19 patients.
Source: Durre Aden, vagisha sharma, sufian zaheer, et al. Netosis -A double-edged sword in the Pathogenesis of LONG COVID. Authorea. April 28, 2023. https://www.authorea.com/users/570888/articles/640398-netosis-a-double-edged-sword-in-the-pathogenesis-of-long-covid (Full text available as PDF file)

Antihistamines as an early treatment for Covid-19

Abstract:

Infection with SARs-COV-2 results in COVID-19 disease. Between March 2020 and August 2021, 468 COVID-19 patients confirmed by PCR or antigen test, in Yepes, Spain, received early treatment with antihistamines, adding azithromycin in selected cases. The primary endpoint is the hospitalization rate of COVID-19 patients, and the secondary endpoints are ICU admission and mortality rates. All endpoints are compared with the official Spanish rates during the time period of the study.

There were 20 hospital admissions (hospitalization rate 4,3%), 5 ICU admissions (ICU admission rate 1,1%) and 3 deaths (fatality rate of 0,6%). No patients in the study required follow up treatment, which suggest they did not develop long COVID. Results from this retrospective trail indicate that early treatment of SARS-COV-2 positive patients with antihistamines may reduce the odds of hospitalization (OR: 0.490, CI: 0.313-0.767, p-value: 0.001). Randomized controlled clinical trials are needed to further evaluate the effects of early antihistamine treatment of SARS-CoV-2 patients to prevent hospitalization, ICU admission, mortality and long-covid.

Source: Morán Blanco JI, Alvarenga Bonilla JA, Fremont-Smith P, Villar Gómez de Las Heras K. Antihistamines as an early treatment for Covid-19. Heliyon. 2023 May;9(5):e15772. doi: 10.1016/j.heliyon.2023.e15772. Epub 2023 Apr 25. PMID: 37128299; PMCID: PMC10129342. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129342/ (Full text)

Long-COVID, is a New Syndrome?

Abstract:

The ongoing or developing new symptoms after acute coronavirus disease-2019 (COVID-19) infection has emerged as a new clinical problem. This has become a problem facing the globally infected population and health systems. “Long-COVID” can be defined as patients with laboratory-confirmed or clinically present COVID-19 whose symptoms persist for four weeks after diagnosis. Symptoms are remarkably heterogeneous, as seen in acute COVID-19. These symptoms may remain stable or fluctuate. Controversy over its definition complicates accurate diagnosis and management of the disease. The most prominent symptoms were fatigue, sleep disturbances, chest pain, and shortness of breath. Recent reports also highlight the risk of long-term sequelae in those recovering from acute COVID-19, affecting almost all organs such as the skin, respiratory system, cardiovascular system, neuropsychiatric system, and renal system. The long-term effects of COVID-19, in hospitalized and non-hospitalized individuals, across all age groups, should be a priority for future research with standardized and controlled studies.

Source: Özlem Alıcı. Long-COVID, is a New Syndrome?. Cam Sakura Med J. 2023; 3(1): 1-5 https://jag.journalagent.com/csmedj/pdfs/CSM_3_1_1_5.pdf (Full text available as PDF file)