Category: Overlapping Illnesses

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)

A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms

Abstract:

Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints.

To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the “sick recovered” from the “healthy recovered.”

Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.

Source: Guest PC, Neyazi A, Braun-Dullaeus RC, Müller P, Schreiber J, Haghikia A, Vasilevska V, Steiner J. A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms. Adv Exp Med Biol. 2023;1412:97-115. doi: 10.1007/978-3-031-28012-2_5. PMID: 37378763. https://pubmed.ncbi.nlm.nih.gov/37378763/

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)

Long COVID in Young Patients: Impact on Lung Volume Evaluated Using Multidetector CT

Abstract:

Purpose: To evaluate using quantitative analysis on chest CT images a possible lung volume reduction in Long COVID patients who complain mild respiratory symptoms, with chest CT negative for inflammatory findings.
Materials and Methods: CT images of patients from 18 to 40 years old who underwent chest CT scan at our institution were analyzed retrospectively, using AwServer Thoracic VCAR software for a quantitative study. Exclusion criteria were inflammatory findings at CT, previous lung surgery, lung cancer, and breath artifacts that invalidate the quality of images. Patients were divided into two groups: in the first one (“post-COVID”) were patients who had previous SARS-CoV-2 infection, confirmed by an RT-PCR, who underwent chest CT from 3 to 6 months after their negativization for long COVID symptoms; in the control group (“non-COVID”), were enrolled patients who underwent a chest CT scan from January 2018 to December 2019, before the spread of COVID in Italy.
Results: Our final population included 154 TC, 77 post-COVID patients (mean age 33 ± 6) and 77 non-COVID patients (mean age 33 ± 4.9). Non statistical significative differences were obtained between groups in terms of age, sex, and other characteristics that affect total lung capacity such as obesity, thoracic malformations, and smoking habit. Mean values of the total lung volume (TV), right-lung volume (RV), and left-lung volume (LV) in the post-COVID group compared with non-COVID group were, respectively: 5.25 ± 0.25 L vs. 5.72 ± 0.26 L (p = 0.01); 2.76 ± 0.14 L vs. 3 ± 0.14 L (p = 0.01); 2.48 ± 0.12 L vs. 2.72 ± 0.12 L (p = 0.01).
Conclusion: In patients with symptoms suggesting Long COVID and negative chest CT macroscopic findings, quantitative volume analysis demonstrated a mean value of reduction in lung volume of 10% compared to patients of the same age who never had COVID. A chest CT negative for inflammatory findings may induce clinicians to attribute Long COVID mild respiratory symptoms to anxiety, especially in young patients. Our study brings us beyond appearances and beyond the classic radiological signs, introducing a quantitative evaluation of lung volumes in these patients. It is hard to establish to what extent this finding may contribute to Long COVID symptoms, but this is another step to gain a wider knowledge of the potential long-term effects caused by this new virus.
Source: Bellini D, Capodiferro P, Vicini S, Rengo M, Carbone I. Long COVID in Young Patients: Impact on Lung Volume Evaluated Using Multidetector CT. Tomography. 2023; 9(4):1276-1285. https://doi.org/10.3390/tomography9040101 https://www.mdpi.com/2379-139X/9/4/101 (Full text)
Source:

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID

Abstract:

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed.
Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI).
Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group.
Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.
Source: Chung TW-H, Zhang H, Wong FK-C, Sridhar S, Lee TM-C, Leung GK-K, Chan K-H, Lau K-K, Tam AR, Ho DT-Y, et al. A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID. Brain Sciences. 2023; 13(7):1014. https://doi.org/10.3390/brainsci13071014 https://www.mdpi.com/2076-3425/13/7/1014 (Full text)

Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives

Abstract:

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. As a result, to monitor the health of individuals affected by these conditions, they must maintain up-to-date health records using digital health informatics apps for surveillance.

In this review, we provide an overview of the existing literature on identifying long COVID manifestations through hierarchical classification and the characterization of long COVID by different hierarchical groups based on the Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) in artificial intelligence (AI) to identify long COVID.

Knowledge exploration, using the concept map for the clinical pathways of long COVID presented in this paper, provides an overview of the data needed to explore tackling the long-term effect of COVID-19 by integrating innovative cohesive frameworks and designing health informatics-based applications. To the best of our knowledge, this is the first paper to explore the potential incorporation of long COVID as a variable risk factor within a digital health informatics application.

Source: Ambalavanan, R.; Snead, R.S.; Marczika, J.; Kozinsky, K.; Aman, E. Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives. Preprints.org2023, 2023062111. https://doi.org/10.20944/preprints202306.2111.v1 https://www.preprints.org/manuscript/202306.2111/v1 (Full text available as PDF file)

Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension

Abstract:

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated.
Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort.
Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40–65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3–6 and 12–18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient’s home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data.
Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3–6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories.
Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.
Source: Baalbaki N, Blankestijn JM, Abdel-Aziz MI, de Backer J, Bazdar S, Beekers I, Beijers RJHCG, van den Bergh JP, Bloemsma LD, Bogaard HJ, et al. Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension. Journal of Personalized Medicine. 2023; 13(7):1060. https://doi.org/10.3390/jpm13071060 https://www.mdpi.com/2075-4426/13/7/1060 (Full text)

Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study

Abstract:

Fatigue and dyspnoea are common post-COVID symptoms. The aim of this study was to apply Sankey plots and exponential bar plots for visualizing the evolution and trajectory of post-COVID fatigue and dyspnoea symptoms in a cohort of previously hospitalized COVID-19 survivors. A total of 1266 previously hospitalized patients due to COVID-19 participated in this multicentre study. They were assessed at hospital admission (T0), 8.4 months (T1), 13.2 months (T2) and 18.3 months (T3) after hospital discharge and were asked about the presence of self-reported fatigue or dyspnoea symptoms.
Fatigue was defined as a self-perceived feeling of constant tiredness and/or weakness whereas dyspnoea was defined as a self-perceived feeling of shortness of breath at rest. We specifically asked for fatigue and dyspnoea that participants attributed to the infection. Clinical/hospitalization data were collected from hospital medical records.
The prevalence of post-COVID fatigue was 56.94% (n = 721) at T1, 52.31% (n = 662) at T2 and 42.66% (n = 540) at T3. The prevalence of dyspnoea at rest decreased from 28.71% (n = 363) at hospital admission (T0), to 21.29% (n = 270) at T1, to 13.96% (n = 177) at T2 and 12.04% (n = 153) at T3. The Sankey plots revealed that 469 (37.08%) and 153 (12.04%) patients exhibited fatigue and dyspnoea at all follow-up periods.
The recovery exponential curves show a decreased prevalence trend, showing that fatigue and dyspnoea recover the following three years after hospitalization. The regression models revealed that the female sex and experiencing the symptoms (e.g., fatigue, dyspnoea) at T1 were factors associated with the presence of post-COVID fatigue or dyspnoea at T2 and T3.
The use of Sankey plots shows a fluctuating evolution of post-COVID fatigue and dyspnoea during the first two years after infection. In addition, exponential bar plots revealed a decreased prevalence of these symptoms during the first years after. The female sex is a risk factor for the development of post-COVID fatigue and dyspnoea.
Source:Fernández-de-las-Peñas C, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Fuensalida-Novo S, Martín-Guerrero JD, Pellicer-Valero OJ, de-la-Llave-Rincón AI. Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study. Biomedicines. 2023; 11(7):1863. https://doi.org/10.3390/biomedicines11071863 https://www.mdpi.com/2227-9059/11/7/1863 (Full text)

The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue

Abstract:

Fatigue and physical exhaustion are the dominant symptoms of post-coronavirus (COVID-19) conditions that might even develop after only mild acute disease. Post-acute infection syndromes have been observed after various infections, e.g., Coxiella burnetii, Ebola, Dengue, Polio, severe acute respiratory syndrome (SARS), Chikungunya, West Nile Virus, Borrelia, or Giardina lamblia. The similarities in symptoms and courses suggest a high likelihood of common pathogenetic pathways, including persistent infection, autoimmune reactions, dysregulation of the microbiome, inability to repair tissue damage, or endothelial dysfunction.

Some herbal drugs, so-called adaptogens, exert effects resulting in an increase in the resistance or regulatory potential of organisms against biological, chemical and physical burden or stress. Therefore, it seems possible that adaptogens can be helpful in cases of post-COVID-19 symptoms. One of these adaptogens is Rhodiola rosea L. The proprietary ethanolic extract made from roots and rhizomes of Rhodiola rosea WS® 1375 has been reported to modulate neuroinflammation in response to stress stimuli in preclinical models. Moreover, it activated the synthesis or resynthesis of adenosine triphosphate (ATP) in skeletal muscle mitochondria and counteracted muscle fatigue.

In three clinical trials with subjects suffering from burnout symptoms, prolonged or chronic fatigue symptoms or life-stress symptoms, clinically relevant improvements of fatigue and exhaustion were reported over 4 to 12 weeks of treatment at a very favorable tolerability and safety profile in heterogeneous patient populations. In conclusion, Rhodiola rosea extract WS® 1375 has a promising pharmacological and therapeutic profile for the treatment of fatigue and physical exhaustion associated with post-COVID-19 conditions.

Source: Wegener T, Edwards D, Kasper S. The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue. hb TIMES Schw Aerztej. 2023;8(1):56-61. doi:10.36000/hbT.2023.09.001 https://schw-aerztej.healthbooktimes.org/article/74319-the-potential-role-of-rhodiola-rosea-l-extract-ws-1375-for-patients-with-post-covid-19-fatigue (Full text)

Chronic inflammation, neuroglia dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Plasmalogens (Pls) are lipids containing a vinyl-ether bond in their glycerol backbone
  • Pls have antioxidant properties and are important for curved membrane assemblies
  • Post-COVID-19 symptoms are highly prevalent and share several features with ME/CFS
  • Pls depletion is a shared biological hallmark of ME/CFS and acute COVID-19 syndrome
  • Pls replacement is a promising tool against neuroinflammation in these two conditions

Abstract:

After five waves of COVID-19 outbreaks, it has been recognized that a significant portion of the affected individuals developed long-term debilitating symptoms marked by chronic fatigue, cognitive difficulties (“brain fog”), post-exertional malaise, and autonomic dysfunction. The onset, progression, and clinical presentation of this condition, generically named post-COVID-19 syndrome, overlap significantly with another enigmatic condition, referred to as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Several pathobiological mechanisms have been proposed for ME/CFS, including redox imbalance, systemic and central nervous system inflammation, and mitochondrial dysfunction. Chronic inflammation and glial pathological reactivity are common hallmarks of several neurodegenerative and neuropsychiatric disorders and have been consistently associated with reduced central and peripheral levels of plasmalogens, one of the major phospholipid components of cell membranes with several homeostatic functions.

Of great interest, recent evidence revealed a significant reduction of plasmalogens contents, biosynthesis, and metabolism in ME/CFS and acute COVID-19, with a strong association to symptom severity and other relevant clinical outcomes. These bioactive lipids have increasingly attracted attention due to their reduced levels representing a common pathophysiological manifestation between several disorders associated with aging and chronic inflammation. However, alterations in plasmalogen levels or their lipidic metabolism have not yet been examined in individuals suffering from post-COVID-19 symptoms.

Here, we proposed a pathobiological model for post-COVID-19 and ME/CFS based on their common inflammation and dysfunctional glial reactivity, and highlighted the emerging implications of plasmalogen deficiency in the underlying mechanisms. Along with the promising outcomes of plasmalogen replacement therapy (PRT) for various neurodegenerative/neuropsychiatric disorders, we sought to propose PRT as a simple, effective, and safe strategy for the potential relief of the debilitating symptoms associated with ME/CFS and post-COVID-19 syndrome.

Source: Chaves AM, Braniff O, Angelova A, Deng Y, Tremblay MÈ. Chronic inflammation, neuroglia dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome. Brain Res Bull. 2023 Jul 7:110702. doi: 10.1016/j.brainresbull.2023.110702. Epub ahead of print. PMID: 37423295. https://www.sciencedirect.com/science/article/pii/S0361923023001272?via%3Dihub (Full text)