Tag: long covid pathophysiology

Understanding the neurological implications of acute and long COVID using brain organoids

Abstract:

As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years.

Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature.

In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.

Source: García-González L, Martí-Sarrias A, Puertas MC, Bayón-Gil Á, Resa-Infante P, Martinez-Picado J, Navarro A, Acosta S. Understanding the neurological implications of acute and long COVID using brain organoids. Dis Model Mech. 2023 Jul 1;16(7):dmm050049. doi: 10.1242/dmm.050049. Epub 2023 Jul 17. PMID: 37458167. https://journals.biologists.com/dmm/article/16/7/dmm050049/323961/Understanding-the-neurological-implications-of  (Full text)

Long COVID, linking etiopathogenic theories

Abstract:

In this letter we discuss the various theories involved in the pathogenesis of Long COVID and how they are closely interrelated, conditioning the full range of symptoms and signs presented by patients affected by this condition, as well as calling for the recognition of the disease by the health authorities that must begin to streamline their health processes to limit the burden of this disease, which tends to be chronic and degenerative.

Source: Luis del Carpio-Orantes, Andrés Aguilar-Silva. Long COVID, linking etiopathogenic theories. Qeios, CC-BY 4.0. https://www.qeios.com/read/A7TYBN (Full text)

Hematological alterations associated with long COVID-19

Abstract:

Long COVID-19 is a condition characterized by persistent symptoms lasting beyond the acute phase of COVID-19. Long COVID-19 produces diverse symptomatology and can impact organs and systems, including the hematological system. Several studies have reported, in COVID-19 patients, hematological abnormalities. Most of these alterations are associated with a higher risk of severe disease and poor outcomes.

This literature review identified studies reporting hematological parameters in individuals with Long COVID-19. Findings suggest that Long COVID-19 is associated with a range of sustained hematological alterations, including alterations in red blood cells, anemia, lymphopenia, and elevated levels of inflammatory markers such as ferritin, D-dimer, and IL-6.

These alterations may contribute to a better understanding of the pathophysiology of Long COVID-19 and its associated symptoms. However, further research is needed to elucidate the underlying mechanisms and potential treatments for these hematological changes in individuals with Long COVID-19.

Source: Lechuga Guilherme C., Giovanni De-Simone Salvatore, Morel Carlos M. Hematological alterations associated with long COVID-19. Frontiers in Physiology, Vol 14, 2023. DOI: 10.3389/fphys.2023.1203472  ISSN: 1664-042X https://www.frontiersin.org/articles/10.3389/fphys.2023.1203472 https://www.frontiersin.org/articles/10.3389/fphys.2023.1203472/full (Full text)

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)

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors

Abstract:

In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10–20% of these survivors have been reported to encounter long-term health problems, defined as ‘long COVID-19’, e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence.
At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation.
Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.
Source: Zaira B, Yulianti T, Levita J. Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors. Current Issues in Molecular Biology. 2023; 45(7):5725-5740. https://doi.org/10.3390/cimb45070361 https://www.mdpi.com/1467-3045/45/7/361 (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

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)

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)

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2

Abstract:

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis.

Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL).

Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)].

Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Source: Mouchati C, Durieux JC, Zisis SN, Labbato D, Rodgers MA, Ailstock K, Reinert BL, Funderburg NT, McComsey GA. Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2. Front Immunol. 2023 May 12;14:1182544. doi: 10.3389/fimmu.2023.1182544. PMID: 37251403; PMCID: PMC10217362. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217362/ (Full text)