Tag: long Covid

The molecular fingerprint of neuroinflammation in COVID-19: A comprehensive discussion on molecular mechanisms of neuroinflammation due to SARS-COV2 antigens

Abstract:

Background and objective: Severe acute respiratory syndrome coronavirus 2 attacks the neural system directly and indirectly via various systems, such as the nasal cavity, olfactory system, and facial nerves. Considering the high energy requirement, lack of antioxidant defenses, and high amounts of metal ions in the brain, oxidative damage is very harmful to the brain. Various neuropathic pain conditions, neurological disorders, and neuropsychiatric complications were reported in Coronavirus disease 2019, prolonged Coronavirus disease 2019, and after Coronavirus disease 2019 immunization. This manuscript offers a distinctive outlook on the interconnectedness between neurology and neuropsychiatry through its meticulous analysis of complications.

Discussion: After recovering from Coronavirus disease 2019, approximately half of the patients reported developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Long Coronavirus disease 2019 imaging reports illustrated the hypometabolism in various parts of the brain, such as olfactory bulbs, limbic/paralimbic domains, the brainstem, and the cerebellum. Ninety imaging and neuropathological studies of Coronavirus disease 2019 have shown evidence of white matter, brainstem, frontotemporal, and oculofrontal lesions. Emotional functions, such as pleasant, long/short-term memory, movement, cognition and cognition in decision-making are controlled by these regions. The neuroinflammation and the mechanisms of defense are well presented in the discussion. The role of microglia activation, Inducible NO synthase, Cyclooxygenases ½, Reactive oxygen species, neurotoxic toxins and pro-inflammatory cytokines, such as Interleukin-1 beta, Interleukin-6 and Tumor Necrosis Factor-alpha are highlighted in neuronal dysfunction and death. Nuclear factor kappa-light-chain-enhancer of activated B cells, Mitogen-activated protein kinase, Activator Protein 1, and Interferon regulatory factors are the main pathways involved in microglia activation in Coronavirus disease 2019 neuroinflammation.

Conclusion: The neurological aspect of Coronavirus disease 2019 should be highlighted. Neurological, psychological, and behavioral aspects of Coronavirus disease 2019, prolonged Coronavirus disease 2019, and Coronavirus disease 2019 vaccines can be the upcoming issues. We need a global awareness where this aspect of the disease should be more considered in health research.

Source: Zayeri ZD, Torabizadeh M, Kargar M, Kazemi H. The molecular fingerprint of neuroinflammation in COVID-19: A comprehensive discussion on molecular mechanisms of neuroinflammation due to SARS-COV2 antigens. Behav Brain Res. 2024 Jan 20;462:114868. doi: 10.1016/j.bbr.2024.114868. Epub ahead of print. PMID: 38246395. https://www.sciencedirect.com/science/article/abs/pii/S016643282400024X

Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022

Abstract:

Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors associated with long COVID and the individual symptoms. Prevalence differences were conducted to examine differences in long COVID by vaccination status.

Overall, more than one in five adults who ever had COVID-19 reported symptoms consistent with long COVID (21.8%). The most common symptom was tiredness or fatigue (26.2%), followed by difficulty breathing or shortness of breath (18.9%), and loss of taste or smell (17.0%). Long COVID was more common among adults under 65 years, women, American Indian or Alaska Native or other/multi race group, smokers, and people with a disability, depression, overweight or obesity compared to their respective counterparts.

The prevalence of long COVID was higher among unvaccinated adults (25.6%) than vaccinated adults (21.6%) overall, and for 20 of 32 subgroups assessed. These findings underscore the benefits of vaccination, the importance of early treatment, and the need to better inform health care resource allocation and support services for those experiencing long COVID.

Source: Nguyen KH, Bao Y, Mortazavi J, Allen JD, Chocano-Bedoya PO, Corlin L. Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022. Vaccines (Basel). 2024 Jan 18;12(1):99. doi: 10.3390/vaccines12010099. PMID: 38250912; PMCID: PMC10820629. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820629/ (Full text)

Long COVID Diagnostic with Differentiation from Chronic Lyme Disease using Machine Learning and Cytokine Hubs

Abstract:

The absence of a diagnostic for long COVID (LC) or post-acute sequelae of COVID-19 (PASC) has profound implications for research and potential therapeutics. Further, symptom-based identification of patients with long-term COVID-19 lacks the specificity to serve as a diagnostic because of the overlap of symptoms with other chronic inflammatory conditions like chronic Lymedisease (CLD), myalgic encephalomyelitis-chronic fatigue syndrome (ME-CFS), and others. Here, we report a machine-learning approach to long COVID diagnosis using cytokine hubs that are also capable of differentiating long COVID from chronic Lyme.

We constructed three tree-based classifiers: decision tree, random forest, and gradient-boosting machine (GBM) and compared their diagnostic capabilities. A 223 patient dataset was partitioned into training (178 patients) and evaluation (45 patients) sets. The GBM model was selected based on performance (89% Sensitivity and 96% Specificity for LC) with no evidence of overfitting.

We tested the GBM on a random dataset of 124 individuals (106 PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity 90% for LC). A Lyme Index composed of two features ((TNF-alpha +IL-4)/(IFN-gamma + IL-2) and (TNF-alpha *IL-4)/(IFN-gamma + IL-2 + CCL3) was constructed as a confirmatory algorithm to discriminate between LC and CLD.

Source: Bruce Patterson, Jose Guevara-Coto, Javier Mora et al. Long COVID Diagnostic with Differentiation from Chronic Lyme Disease using Machine Learning and Cytokine Hubs, 18 January 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3873244/v1] https://www.researchsquare.com/article/rs-3873244/v1 (Full text)

Long Covid

Abstract:

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID.

Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children.

The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored.

Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.

Source: Asiya Kamber Zaidi and Puya Dehgani-Mobaraki. Long Covid. Progress in Molecular Biology and Translational Science, Volume 202, 2024, Pages 113-125 https://www.sciencedirect.com/science/article/abs/pii/S1877117323001771

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

Abstract:

Background: As about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.

Method: To this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.

Results: None of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).

Conclusions: Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.

Source: Cezar R, Kundura L, André S, Lozano C, Vincent T, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Loubet P, Sotto A, Tran TA, Estaquier J, Corbeau P. T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID. Front Immunol. 2024 Jan 3;14:1335352. doi: 10.3389/fimmu.2023.1335352. PMID: 38235145; PMCID: PMC10791767. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791767/ (Full text)

Psychometric evaluation of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) among adults with Long COVID, ME/CFS, and healthy controls: A machine learning approach

Abstract:

Long COVID shares a number of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including post-exertional malaise, severe fatigue, and neurocognitive deficits. Utilizing validated assessment tools that accurately and efficiently screen for these conditions can facilitate diagnostic and treatment efforts, thereby improving patient outcomes.

In this study, we generated a series of random forest machine learning algorithms to evaluate the psychometric properties of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) in classifying large groups of adults with Long COVID, ME/CFS (without Long COVID), and healthy controls.

We demonstrated that the DSQ-SF can accurately classify these populations with high degrees of sensitivity and specificity. In turn, we identified the particular DSQ-SF symptom items that best distinguish Long COVID from ME/CFS, as well as those that differentiate these illness groups from healthy controls.

Source: McGarrigle WJ, Furst J, Jason LA. Psychometric evaluation of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) among adults with Long COVID, ME/CFS, and healthy controls: A machine learning approach. J Health Psychol. 2024 Jan 28:13591053231223882. doi: 10.1177/13591053231223882. Epub ahead of print. PMID: 38282368. https://pubmed.ncbi.nlm.nih.gov/38282368/

The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study

Abstract:

Long Covid-19 syndrome (LCS) manifests with a wide range of clinical symptoms, yet the factors associated with LCS remain poorly understood. The current study aimed to investigate the relationships that demographic characteristics, clinical history, laboratory indicators, and the frequency of HLA-I alleles have with the likelihood of developing LCS.

We extracted the demographic characteristics and clinical histories from the medical records of 88 LCS cases (LCS+ group) and 96 individuals without LCS (LCS− group). Furthermore, we evaluated the clinical symptoms, serum levels of interleukin (IL)-6 and tumor necrosis factor-α, laboratory parameters, and the frequencies of HLA-I alleles.

Following this we used multiple logistic regression to investigate the association these variables had with LCS. Subjects in the LCS+ group were more likely to have experienced severe Covid-19 symptoms and had higher body mass index (BMI), white blood cell, lymphocyte counts, C-reactive protein (CRP), and IL-6 levels than those in the LCS− group (for all: P < 0.05).

Moreover, the frequencies of the HLA-A*11, -B*14, -B*38, -B*50, and -C*07 alleles were higher in the LCS+ group (for all: P < 0.05). After adjusting for the most important variables, the likelihood of suffering from LCS was significantly associated with BMI, CRP, IL-6, the HLA-A*11, and -C*07 alleles, as well as a positive history of severe Covid-19 (for all: P < 0.05).

Our study showed that a history of severe Covid-19 during the acute phase of the disease, the HLA-A*11, and -C*07 alleles, higher BMI, as well as elevated serum CRP and IL-6 levels, were all associated with an increased likelihood of LCS.

Source: Torki, E., Hoseininasab, F., Moradi, M. et al. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med 24, 1 (2024). https://doi.org/10.1007/s10238-023-01256-1 https://link.springer.com/article/10.1007/s10238-023-01256-1 (Full text)

Long COVID in pediatrics-epidemiology, diagnosis, and management

Abstract:

This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID — at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities.

Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.

Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions.

Source: Toepfner N, Brinkmann F, Augustin S, Stojanov S, Behrends U. Long COVID in pediatrics-epidemiology, diagnosis, and management. Eur J Pediatr. 2024 Jan 27. doi: 10.1007/s00431-023-05360-y. Epub ahead of print. PMID: 38279014. https://link.springer.com/article/10.1007/s00431-023-05360-y (Full text available as PDF file)

Confirmation of COVID-19 infection status and reporting of Long COVID symptoms in a population-based birth cohort: No evidence of a nocebo effect

Abstract:

Some patients with COVID-19 develop symptoms after the acute infection, known as ‘Long COVID’. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort.
We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test vs unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators.
There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.
Source: 1.
Macleod-Hall CI, Munafò MR, Dyer ML. Confirmation of COVID-19 infection status and reporting of Long COVID symptoms in a population-based birth cohort: No evidence of a nocebo effect. Journal of Health Psychology. 2024;0(0). doi:10.1177/13591053241228711 https://journals.sagepub.com/doi/10.1177/13591053241228711

Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS

Abstract:

Post-COVID Syndrome (PCS) refers to a diverse array of symptoms that persist beyond 3 months of the acute phase of a SARS-CoV-2 infection. The most frequent symptom is fatigue, which can manifest both mentally and physically. In this study, handgrip strength (HGS) parameters were determined as an objective measure of muscle fatigue and fatigability. HGS parameters were correlated with other frequent symptoms among 144 female PCS patients suffering from fatigue, exertional intolerance, and cognitive impairment.

Seventy-eight patients met the Canadian Consensus Criteria (CCC) for post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disability and key symptoms were evaluated utilizing self-reported questionnaires.

Notably, patients diagnosed with ME/CFS exhibited a higher overall severity of symptoms, including lower physical function (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), post-exertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004). While HGS was similarly impaired in both PCS and ME/CFS patients, the associations between HGS and the severity of symptoms and disability revealed striking differences.

We observed significant correlations of HGS parameters with physical function across all patients, but with the key symptoms PEM, fatigue, cognitive impairment, and autonomic dysfunction in ME/CFS patients only. This points to a common mechanism for these symptoms in the ME/CFS subtype, distinct from that in other types of PCS. Further HGS provides an objective marker of disease severity in ME/CFS.

Source: Anna Paffrath, Laura Kim, Claudia Kedor, Elisa Stein, Rebekka Rust, Helma Freitag, Uta Hoppmann, Leif G Hanitsch, Judith Bellmann-Strobl, Kirsten Wittke, Carmen Scheibenbogen, Franziska Sotzny. Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS.
medRxiv 2024.01.25.24301776;  https://www.medrxiv.org/content/10.1101/2024.01.25.24301776v1 (Full text available as PDF file)