Tag: long covid symptoms

Carotid body dysregulation contributes to the enigma of long COVID

Abstract:

The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID. During cardiopulmonary exercise testing, the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group than in the controls, indicating excessive hyperventilation.

The hypoxic ventilatory response, which measures carotid chemoreflex sensitivity, was increased in long COVID participants and correlated with the VE/VCO2 slope, suggesting that excessive hyperventilation may be related to carotid body hypersensitivity. Therefore, the carotid chemoreflex is sensitized in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.

Source: Ahmed El-Medany, Zoe H Adams, Hazel C Blythe, Katrina A Hope, Adrian H Kendrick, Ana Paula Abdala Sheikh, Julian FR Paton, Angus K Nightingale, Emma C Hart. Carotid body dysregulation contributes to the enigma of long COVID. medRxiv 2023.05.25.23290513; doi: https://doi.org/10.1101/2023.05.25.23290513 https://www.medrxiv.org/content/10.1101/2023.05.25.23290513v1.full-text (Full text)

Role of Vitamin D Supplementation for Symptoms and Lung Function Improvement in Long COVID Patient

Abstract:

Post-Acute COVID-19 Syndrome (PACS) or acute post-COVID-19 syndrome or also known as “Long Covid”, is a collection of persistent symptoms and long-term complications more than four weeks after the onset of initial symptoms. One of the leading causes of these long-term complications is pulmonary fibrosis, with an incidence of almost 25% in patients a year after hospitalization. Vitamin D is an important substance to our body homeostasis and regulation. Vitamin D has pleiotropic effect as pulmonary antifibrosis. This research aims to directly provide vitamin D3 supplements, especially in improving lung function in pulmonary fibrosis patients after COVID-19 infection.

This study was a one-group, quasiexperimental pretest-posttest design conducted at Labuang Baji hospitals in the eastern part of Indonesia. The population of this study was patients post-covid-19 infection with negative PCR results at least three months, had persistent symptoms of covid 19, and a CT scan confirmed pulmonary fibrosis or destroyed lung results. Lung function was measured using spirometry before and after the intervention (Vitamin D3 5000 IU supplementation with a frequency of once per day for two months). This study included 20 cases of Lung Fibrosis post-Covid-19. The majority of respondents were women and between the ages of 40 and 49. Among 20 patients, most of them fatigue or dyspneu or shortness of breath as their main symptoms.

After 2-months supplementation of Vitamin D 5000 IU, number of patients who had shortness of breath and fatigue reduced significantly (From 11 to 3 and from 11 to 2 patients, respectively). 85% of our patient had deficient-insufficient status of vitamin D. We found restrictive pattern as a dominant lung function in our patient. There was significant improvement in lung function status after 2-months vitamin D supplementation (p=0.02). Vitamin D supplementation for Long COVID may have benefit for symptoms and lung function improvement.

Source: Irawaty Djaharuddin, Muzakkir Amir, Jamaluddin Madolangan, Ahmad Fachry Toaha, Muthiah Nur Afifah, Muhammad Zaki Rahmani, Izza fauziah Irfan.Role of Vitamin D Supplementation for Symptoms and Lung Function Improvement in Long COVID Patient. Teikyo Medical Journal. Volume 45, Issue 09, November, 2022 https://www.teikyomedicaljournal.com/volume/TMJ/45/10/role-of-vitamin-d-supplementation-for-symptoms-and-lung-function-improvement-in-long-covid-patient-638db40f96abb.pdf (Full text)

Antihistamines improve cardiovascular manifestations and other symptoms of Long-COVID attributed to Mast Cell Activation

Abstract:

Introduction: Long-COVID is a hardly defined condition and there are no effective therapies. Cardiovascular manifestations of Long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of Long-COVID, including in the mechanisms of its cardiovascular manifestations. The aim of the study was to evaluate the effectiveness of a treatment with blockers of histamine receptors in Long-COVID patients who did not respond to other therapies.

Methods: Fourteen patients (F/M=9/5; 49.5±11.5 years) and 13 controls (F/M=8/5; 47.3±8.0 years) with Long-COVID symptoms attributed to MCA were evaluated. Patients were treated with fexofenadine (180 mg/day) and famotidine (40 mg/day). Fatigue, brain fog, abdominal disorders, and increased heart rate were evaluated in treated and untreated patients at baseline and 20 days later.

Results: Long-COVID symptoms disappeared completely in 29% of treated patients. There was significant improvement in each of the considered symptoms (improved or disappeared) in all treated patients, and the improvement grade was significantly greater in treated patients with respect to controls. No significant differences in the outcomes were observed in the controls.

Our data confirm that histamine receptors blockade may be an effective target to successfully treat long-COVID. Our finding supports the underlying role of MCA in the pathophysiology of Long-COVID.

Source: Fabrizio Salvucci, Roberto Codella, ADRIANA COPPOLA, Irene Zacchei, Gabriella Grassi, Maria L. Anti, Nicolita Nitisoara, Livio Luzi, and Carmine Gazzaruso. Antihistamines improve cardiovascular manifestations and other symptoms of Long-COVID attributed to Mast Cell Activation. Front. Cardiovasc. Med. Sec. General Cardiovascular Medicine. Volume 10 – 2023 | doi: 10.3389/fcvm.2023.1202696 https://www.frontiersin.org/articles/10.3389/fcvm.2023.1202696/abstract

Long COVID, the Brain, Nerves, and Cognitive Function

Abstract:

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms.
Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies.
This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored.
Source: Reiss AB, Greene C, Dayaramani C, Rauchman SH, Stecker MM, De Leon J, Pinkhasov A. Long COVID, the Brain, Nerves, and Cognitive Function. Neurology International. 2023; 15(3):821-841. https://doi.org/10.3390/neurolint15030052 https://www.mdpi.com/2035-8377/15/3/52 (Full text)

Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019

Abstract:

Fatigue from post-acute sequelae of coronavirus disease 2019 is a complex constellation of symptoms that could be driven by a wide spectrum of underlying etiologies. Despite this, there seems to be hope for treatment plans that focus on addressing possible etiologies and creating a path to improving quality of life and a paced return to activity.

Source: Abbott Z, Summers W, Niehaus W. Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019. Phys Med Rehabil Clin N Am. 2023 Aug;34(3):607-621. doi: 10.1016/j.pmr.2023.04.006. Epub 2023 Apr 24. PMID: 37419535; PMCID: PMC10123359. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123359/ (Full text)

Determinants of the Onset and Prognosis of the Post-COVID-19 Condition: A 2-Year Prospective Cohort Study

Abstract:

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or “Long COVID”. The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. In a large crossectional evaluation, the RECOVER study in the US identified four clusters of subjects with PCC according to their presenting symptoms. The long-term clinical implications of PCC remain unknown.

Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modeled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach.

Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16·5 – 23·5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7·6%) recovered from PCC during follow-up; almost all of them (n=24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC.

Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, predict the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems.

Source: Mateu, Lourdes and Tebe, Cristian and Loste, Cora and Santos, José Ramón and Lladós, Gemma and López, Cristina and España-Cueto, Sergio and Toledo, Ruth and Font, Marta and Chamorro, Anna and Muñoz-López, Francisco and Nevot, Maria and Vallejo, Nuria and Teis, Albert and Puig, Jordi and Fumaz, Carmina Rodríguez and Muñoz-Moreno, José Antonio and Prats, Anna and Estany-Quera, Carla and Coll-Fernández, Roser and Herrero, Cristina and Casares, Patricia and Garcia, Anna and Paredes, Roger and Clotet, Bonaventura and Massanella, Marta, Determinants of the Onset and Prognosis of the Post-COVID-19 Condition: A 2-Year Prospective Cohort Study. Available at SSRN: https://ssrn.com/abstract=4505315 or http://dx.doi.org/10.2139/ssrn.4505315 (Full text available as PDF file)

The immunology of long COVID

Abstract:

Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge.

Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities.

Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.

Source: Altmann, D.M., Whettlock, E.M., Liu, S. et al. The immunology of long COVID. Nat Rev Immunol (2023). https://doi.org/10.1038/s41577-023-00904-7 https://www.nature.com/articles/s41577-023-00904-7 (Full text)

Long COVID prevalence and impact on quality of life 2 years after acute COVID-19

Abstract:

There has been an increasing interest in the long-term impact of long COVID. However, only a few studies have investigated the clinical manifestations of long COVID after 24 months of acute infection. In this study, prospective online surveys were conducted in adults previously diagnosed with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13, 2020, at 6, 12, and 24 months after COVID-19.

We investigated self-reported symptoms and the EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys. After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis. Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%), insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the incidence of long COVID at 24 months in terms of the number of vaccinations received.

Although the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants. Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time, and COVID-19 vaccination or the number of vaccinations received may not significantly affect the incidence of long COVID.

Source: Kim Y, Bae S, Chang HH, Kim SW. Long COVID prevalence and impact on quality of life 2 years after acute COVID-19. Sci Rep. 2023 Jul 11;13(1):11207. doi: 10.1038/s41598-023-36995-4. PMID: 37433819. https://www.nature.com/articles/s41598-023-36995-4 (Full text)

Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or “brain fog”. Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein–Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms.

Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID.

In addition, the author discusses potential therapeutic approaches based on the gut–brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.

Source: Hashimoto, K. Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02161-5 https://www.nature.com/articles/s41380-023-02161-5 (Full text)

Long COVID and its cardiovascular consequences: What is known?

Abstract:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems.

This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Source: Składanek JA, Leśkiewicz M, Gumiężna K, Baruś P, Piasecki A, Klimczak-Tomaniak D, Sygitowicz G, Kochman J, Grabowski M, Tomaniak M. Long COVID and its cardiovascular consequences: What is known? Adv Clin Exp Med. 2023 Jun 30. doi: 10.17219/acem/167482. Epub ahead of print. PMID: 37386857. https://advances.umw.edu.pl/en/ahead-of-print/167482/ (Full text)