Tag: 2024

Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection

Abstract:

Background: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19.

Methods: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL.

Results: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (β=-0.080, p = 0.001) and long COVID (β=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (β=-0.147, p = 0.026) and long (β=-0.186, p < 0.001) COVID.

Conclusion: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.

Source: Soare IA, Ansari W, Nguyen JL, Mendes D, Ahmed W, Atkinson J, Scott A, Atwell JE, Longworth L, Becker F. Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection. Health Qual Life Outcomes. 2024 Jan 30;22(1):12. doi: 10.1186/s12955-024-02230-5. PMID: 38287294; PMCID: PMC10826014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826014/ (Full text)

Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe

Abstract:

Background: Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study.

Methods: A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe’s (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID.

Results: Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents’ place of residence.

Conclusion: Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

Source: Wilk P, Stranges S, Cuschieri S. Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe. Int J Obes (Lond). 2024 Jan 29. doi: 10.1038/s41366-024-01477-8. Epub ahead of print. PMID: 38287094. https://pubmed.ncbi.nlm.nih.gov/38287094/

Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C

Abstract:

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC.

We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence.

Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.

Source: Alexander Preiss, Abhishek Bhatia, Chengxi Zang, Leyna V. Aragon, John M. Baratta, Monika Baskaran, Frank Blancero, M. Daniel Brannock, Robert F. Chew, Iván Díaz, Megan Fitzgerald, Elizabeth P. Kelly, Andrea Zhou, Mark G. Weiner, Thomas W. Carton, Fei Wang, Rainu Kaushal, Christopher G. Chute, Melissa Haendel, Richard Moffitt, Emily Pfaff. Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C. medRxiv 2024.01.20.24301525; doi: https://doi.org/10.1101/2024.01.20.24301525 https://www.medrxiv.org/content/10.1101/2024.01.20.24301525v1.full-text (Full text)

The Microbiota in Long COVID

Abstract:

Interest in the coronavirus disease 2019 (COVID-19) has progressively decreased lately, mainly due to the great effectivity of vaccines. Furthermore, no new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants able to circumvent the protection of these vaccines, while presenting high transmissibility and/or lethality, have appeared. However, long COVID has emerged as a huge threat to human health and economy globally.
The human microbiota plays an important role in health and disease, participating in the modulation of innate and adaptive immune responses. Thus, multiple studies have found that the nasopharyngeal microbiota is altered in COVID-19 patients, with these changes associated with the onset and/or severity of the disease.
Nevertheless, although dysbiosis has also been reported in long COVID patients, mainly in the gut, little is known about the possible involvement of the microbiota in the development of this disease. Therefore, in this work, we aim to fill this gap in the knowledge by discussing and comparing the most relevant studies that have been published in this field up to this point.
Hence, we discuss that the relevance of long COVID has probably been underestimated, and that the available data suggest that the microbiota could be playing a pivotal role on the pathogenesis of the disease. Further research to elucidate the involvement of the microbiota in long COVID will be essential to explore new therapeutic strategies based on manipulation of the microbiota.
Source: Álvarez-Santacruz C, Tyrkalska SD, Candel S. The Microbiota in Long COVID. International Journal of Molecular Sciences. 2024; 25(2):1330. https://doi.org/10.3390/ijms25021330 https://www.mdpi.com/1422-0067/25/2/1330 (Full text)

Procedural Motor Memory Deficits in Patients With Long-COVID

Abstract:

Background and objectives: At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms (“Long-COVID”) including “brain fog” and deficits in declarative memory. It is not known if Long-COVID affects patients’ ability to form and retain procedural motor skill memories. The objective was to determine the ability of patients with Long-COVID to acquire and consolidate a new procedural motor skill over 2 training days. The primary outcome was to determine difference in early learning, measured as the increase in correct sequence typing speed over the initial 11 practice trials of a new skill. The secondary outcomes were initial and final typing speed on days 1 and 2, learning rate, overnight consolidation, and typing accuracy.

Methods: In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days (NCT05746624). Patients with Long-COVID (reporting persistent post-coronavirus disease 2019 [COVID-19] symptoms for more than 4 weeks) were recruited at the NIH. Patients were matched one-to-one by age and sex to controls recruited during the pandemic using a crowd-sourcing platform. Selection criteria included age 18-90 years, English speaking, right-handed, able to type with the left hand, denied active fever or respiratory infection, and no previous task exposure. Data were also compared with an age-matched and sex-matched control group who performed the task online before the COVID-19 pandemic (prepandemic controls).

Results: In total, 105 of 236 patients contacted agreed to participate and completed the experiment (mean ± SD age 46 ± 12.8 years, 82% female). Both healthy control groups had 105 participants (mean age 46 ± 13.1 and 46 ± 11.9 years, 82% female). Early learning was comparable across groups (Long-COVID: 0.36 ± 0.24 correct sequences/second, pandemic controls: 0.36 ± 0.53 prepandemic controls: 0.38 ± 0.57, patients vs pandemic controls [CI -0.068 to 0.067], vs prepandemic controls [CI -0.084 to 0.052], and between controls [CI -0.083 to 0.053], p = 0.82). Initial and final typing speeds on days 1 and 2 were slower in patients than controls. Patients with Long-COVID showed a significantly reduced overnight consolidation and a nonsignificant trend to reduced learning rates.

Discussion: Early learning was comparable in patients with Long-COVID and controls. Anomalous initial performance is consistent with executive dysfunction. Reduction in overnight consolidation may relate to deficits in procedural memory formation.

Source: Hayward W, Buch ER, Norato G, Iwane F, Dash D, Salamanca-Girón RF, Bartrum E, Walitt B, Nath A, Cohen LG. Procedural Motor Memory Deficits in Patients With Long-COVID. Neurology. 2024 Feb 13;102(3):e208073. doi: 10.1212/WNL.0000000000208073. Epub 2024 Jan 18. PMID: 38237090. https://pubmed.ncbi.nlm.nih.gov/38237090/

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)