Tag: 2023

The Role of Interferons in Long Covid Infection

Abstract:

Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia.

There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology.

In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.

Source: Karbalaeimahdi M, Farajnia S, Bargahi N, Ghadiri-Moghaddam F, Rasouli Jazi HR, Bakhtiari N, Ghasemali S, Zarghami N. The Role of Interferons in Long Covid Infection. J Interferon Cytokine Res. 2023 Feb;43(2):65-76. doi: 10.1089/jir.2022.0193. PMID: 36795973. https://pubmed.ncbi.nlm.nih.gov/36795973/

Association of Post-COVID-19 Condition Symptoms and Employment Status

Abstract:

Importance: Little is known about the functional correlates of post-COVID-19 condition (PCC), also known as long COVID, particularly the relevance of neurocognitive symptoms.

Objective: To characterize prevalence of unemployment among individuals who did, or did not, develop PCC after acute infection.

Design, setting, and participants: This survey study used data from 8 waves of a 50-state US nonprobability internet population-based survey of respondents aged 18 to 69 years conducted between February 2021 and July 2022.

Main outcomes and measures: The primary outcomes were self-reported current employment status and the presence of PCC, defined as report of continued symptoms at least 2 months beyond initial month of symptoms confirmed by a positive COVID-19 test.

Results: The cohort included 15 308 survey respondents with test-confirmed COVID-19 at least 2 months prior, of whom 2236 (14.6%) reported PCC symptoms, including 1027 of 2236 (45.9%) reporting either brain fog or impaired memory. The mean (SD) age was 38.8 (13.5) years; 9679 respondents (63.2%) identified as women and 10 720 (70.0%) were White. Overall, 1418 of 15 308 respondents (9.3%) reported being unemployed, including 276 of 2236 (12.3%) of those with PCC and 1142 of 13 071 (8.7%) of those without PCC; 8229 respondents (53.8%) worked full-time, including 1017 (45.5%) of those with PCC and 7212 (55.2%) without PCC. In survey-weighted regression models excluding retired respondents, the presence of PCC was associated with a lower likelihood of working full-time (odds ratio [OR], 0.71 [95% CI, 0.63-0.80]; adjusted OR, 0.84 [95% CI, 0.74-0.96]) and with a higher likelihood of being unemployed (OR, 1.45 [95% CI, 1.22-1.73]; adjusted OR, 1.23 [95% CI, 1.02-1.48]). The presence of any cognitive symptom was associated with lower likelihood of working full time (OR, 0.70 [95% CI, 0.56-0.88]; adjusted OR, 0.75 [95% CI, 0.59-0.84]).

Conclusions and relevance: PCC was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. The presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to treat and manage PCC symptoms.

Source: Perlis RH, Lunz Trujillo K, Safarpour A, Santillana M, Ognyanova K, Druckman J, Lazer D. Association of Post-COVID-19 Condition Symptoms and Employment Status. JAMA Netw Open. 2023 Feb 1;6(2):e2256152. doi: 10.1001/jamanetworkopen.2022.56152. PMID: 36790806; PMCID: PMC9932847. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932847/(Full text)

STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol

Abstract:

Introduction: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace.

Methods and analysis: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as “standard of care” in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately.

Ethics and dissemination: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations.

Trial registration number: ISRCTN10665760.

Source: Forshaw D, Wall EC, Prescott G, Dehbi HM, Green A, Attree E, Hismeh L, Strain WD, Crooks MG, Watkins C, Robson C, Banerjee R, Lorgelly P, Heightman M, Banerjee A; STIMULATE-ICP trial team. STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol. PLoS One. 2023 Feb 15;18(2):e0272472. doi: 10.1371/journal.pone.0272472. PMID: 36791116; PMCID: PMC9931100. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931100/ (Full text)

Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study

Abstract:

Objective: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition.

Study design: This was a cross-sectional questionnaire-based survey.

Methods: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses.

Results: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (β = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (β = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (β = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (β = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (β = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (β = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (β = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (β = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (β = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (β = -0.51, 95% CI = -0.94 to -0.09).

Conclusions: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

Source: Morioka S, Tsuzuki S, Maruki T, Terada M, Miyazato Y, Kutsuna S, Saito S, Shimanishi Y, Takahashi K, Sanada M, Ashida S, Akashi M, Kuge C, Osanai Y, Tanaka K, Suzuki M, Hayakawa K, Ohmagari N. Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study. Public Health. 2023 Feb 13;216:39-44. doi: 10.1016/j.puhe.2023.01.008. Epub ahead of print. PMID: 36791649. https://www.sciencedirect.com/science/article/pii/S0033350623000173?via%3Dihub (Full text)

Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study

Abstract:

Symptoms of long COVID-19 syndrome (long COVID-19) are reported by 80% of convalescents up to several months after contracting the coronavirus-19 disease (COVID-19). The study aimed to assess the frequency and correlations of long COVID symptoms with sex, disease severity, time since the onset of the disease, and exercise capacity in a population of Polish convalescents hospitalized as a part of a rehabilitation program after COVID-19.

The retrospective analysis was carried out based on medical records concerning reported symptoms, comorbidities, exercise capacity, fatigue and dyspnea on Borg’s scale, arterial oxygen saturation (SpO2), spirometric parameters, chest X-rays/computed tomography scans, systolic pulmonary artery pressure, and left ventricular ejection fraction. The study involved 471 patients aged 63.83 ± 9.93 years who had been hospitalized 191.32 ± 75.69 days from the onset of COVID-19, of which 269 (57.1%) were women. The most common symptoms were fatigue (99.57%), dyspnea (99.36%), and myalgia (97.03%). Women reported more symptoms than men (p < 0.001) and rated their fatigue as more severe (p = 0.021). Patients with depressed moods reported more physical symptoms than others (p < 0.001).

Most long COVID symptoms, including dyspnea, fatigue, and depressive symptoms, were found with the same frequency in patients 12-24 weeks and >24 weeks after recovery (p = 0.874, p = 0.400, and p = 0.320, respectively), regardless of acute COVID-19 severity (p = 0.240, p = 0.826, and p = 0.108, respectively). Dyspnea severity correlated with forced vital capacity (FVC) (r = -0.153, p = 0.005), and forced expiratory volume in one second (FEV1) (r = -0.142, p = 0.008). Fatigue severity correlated with impaired FVC and FEV1 (both r = -0.162, p = 0.003). Fatigue and dyspnea inversely correlated with the distance in a six-minute walk test (r = -0.497, p < 0.001, and r = -0.327, p < 0.001).

In conclusion, in our cohort, long COVID symptoms are more common in women. Dyspnea/fatigue and depressive symptoms do not tend to subside after an average six-month recovery period. The intensity of perceived fatigue may be exaggerated by the coexistence of neuropsychiatric disorders. Increased fatigue and dyspnea correlate with impaired spirometric parameters and significantly affects convalescents’ exercise capacity.

Source: Paradowska-Nowakowska E, Łoboda D, Gołba KS, Sarecka-Hujar B. Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study. Life (Basel). 2023 Feb 11;13(2):508. doi: 10.3390/life13020508. PMID: 36836865; PMCID: PMC9961608. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961608/ (Full text)

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19

Abstract:

Background: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

Method: Data from four releases of the Census Bureau’s Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

Results: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

Conclusions: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Source: Jacobs MM, Evans E, Ellis C. Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19. J Natl Med Assoc. 2023 Feb 13:S0027-9684(23)00025-1. doi: 10.1016/j.jnma.2023.01.016. Epub ahead of print. PMID: 36792456; PMCID: PMC9923441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923441/ (Full text)

Mental health among children with long COVID during the COVID-19 pandemic

Abstract:

A growing number of studies report that persons of all ages, infected with SARS-CoV-2, may experience long-term persistent symptoms, known as long COVID (LC) or post COVID-19 condition. This is one of the first studies examining the consequences of LC on children’s mental health. In this case-control study, we compared select mental health aspects of 103 children diagnosed with LC to a control group of 113 children uninfected with SARS-COV-2; all 4-18 years old. Both groups were assessed via parents’ questionnaires.

In comparison to the control group, children with LC exhibited more memory difficulties. However, no group differences emerged in other functional aspects (connection with friends and engagement in physical activities), problems with concentration, or levels of emotional-behavioral problems (externalizing, internalizing, ADHD, and PTSD symptoms).

We also found that children with LC had greater exposure to COVID-19-related stressors. Higher levels of parental worries regarding their children’s functioning and economic difficulties at home significantly predicted higher levels of children’s emotional-behavioral problems and were better predictors than the child’s age, social functioning, or LC diagnosis.

Conclusion: LC was associated with impairments in some aspects of children’s memory which may relate to academic functioning, but not with higher rates of emotional-behavioral problems, thus warranting interventional programs addressing school functioning and cognitive abilities in this population. Additionally, parents’ economic stress and worries regarding their child’s emotional adjustment during the pandemic, are important factors affecting pandemic-related emotional-behavioral problems among children, regardless of COVID-19 infection, that should be addressed.

What is Known:

• Children may have long COVID (LC) after being infected with SARS-COV-2.

What is New:

• LC may be associated to impairments in some aspects of children’s memory, as reported by parents.

• Parents’ economic stress and worries concerning their children’s emotional adjustment during the pandemic are associated with more distress in their children.

Source: Shachar-Lavie I, Shorer M, Segal H, Fennig S, Ashkenazi-Hoffnung L. Mental health among children with long COVID during the COVID-19 pandemic. Eur J Pediatr. 2023 Feb 14:1–9. doi: 10.1007/s00431-023-04854-z. Epub ahead of print. PMID: 36786887; PMCID: PMC9925927. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925927/ (Full text)

Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles

Abstract:

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2.

Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways.

We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Source: Tom Aschman, Emanuel Wyler, Oliver Baum, Andreas Hentschel, Franziska Legler, Corinna Preusse, Lil Meyer-Arndt, Ivana Büttnerova, Alexandra Förster, Derya Cengiz, Luiz Gustavo Teixeira Alves, Julia Schneider, Claudia Kedor, Rebecca Rust, Judith Bellmann-Strobl, Sanchin Aminaa, Peter Vajkoczy, Hans-Hilmar Goebel, Markus Landthaler, Victor Corman, Andreas Roos, Frank L. Heppner, Helena Radbruch, Friedemann Paul, Carmen Scheibenbogen, Werner Stenzel, Nora F. Dengler. Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles. medRxiv 2023.02.15.23285584; doi: https://doi.org/10.1101/2023.02.15.23285584 https://www.medrxiv.org/content/10.1101/2023.02.15.23285584v1.full-text (Full text)

Decolonization of staphylococcus aureus and therapeutic test to assist the diagnosis in me/cfs, long covid, post-vaccine covid syndrome and other diseases with fatigue and/or chronic pain

Abstract:

Nasal Decolonization is performed with an antiseptic such as Povidone-iodine. For the Therapeutic Test an Antibiotic such as Flucloxacillin plus Probiotics or other supplements with an effect against S.aureus is indicated.

There is a Subgroup of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID Syndrome or PACS who present a persistent bacterial infection that affects the upper respiratory tract, and especially at the level of the nostrils.

We estimate that this Subgroup of patients presenting this persistent infection as a causal or contributing factor would be around a third of all cases.

The most frequent causative agent of these persistent and/or recurrent infections is the Staphylococcus aureus bacterium. According to the studies carried out, this bacterium is present in the nasal passages of between 16 and 36% of the general population, who are asymptomatic carriers of Staphylococcus aureus, and are often unaware of it.

In health professionals who carry out care work, the percentage of carriers can exceed 50%. In a recent study carried out in health workers and medical students, 65% of nasal carriers of S. aureus were reported, and of these, 74% were multidrug-resistant (MDR) bacteria and 69% were biofilm-forming bacteria [1].

Source: Gustavo Aguirre Chang and Aurora Natividad Trujillo Figueredo. Decolonization of staphylococcus aureus and therapeutic test to assist the diagnosis in me/cfs, long covid, post-vaccine covid syndrome and other diseases with fatigue and/or chronic pain. ResearchGate [Preprint] 2/17/23. https://www.researchgate.net/publication/368646387_DECOLONIZATION_OF_STAPHYLOCOCCUS_AUREUS_AND_THERAPEUTIC_TEST_TO_ASSIST_THE_DIAGNOSIS_IN_MECFS_LONG_COVID_POST-VACCINE_COVID_SYNDROME_AND_OTHER_DISEASES_WITH_FATIGUE_ANDOR_CHRONIC_PAIN (Full text)

A narrative inquiry into the school experiences of teenagers living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex chronic medical condition, affecting up to 2% of secondary school aged children in the UK (Collard & Murphy, 2020). It is an illness that has historically been contested and is widely misunderstood, contributing to negative stereotyping and stigma (Blease et al, 2017). Together with the physical symptoms of a complex illness, this has significant implications for the school experiences of young people with ME/CFS.
Using a social constructionist framework that recognises that knowledge creation is a shared enterprise, this research adopts a social justice perspective, which shapes the entirety of the research process.

Adopting Narrative Inquiry as a methodology, this study explores the stories constructed by three young people with ME/CFS, aged between sixteen and seventeen, in relation to their school experiences. The young people used audio or written diaries to construct their narratives and participate in an optional follow up reflective interview.

The young people’s narratives were analysed using the Listening Guide (Brown & Gilligan, 1993), a ‘Voice Centred Relational Method’, revealing the complex, unique and subjective nature of individual experience. Bronfenbrenner’s ecological systems theory (1979) and Ryan and Deci’s Self-determination theory (2017) were used as explanatory frameworks to illustrate the findings, which indicated that understanding, communication and flexibility of adaptations were key factors shaping the young people’s experiences of school. A model for practice has been created for Educational Psychologists to consider using with schools, in order to identify factors within the young people’s environmental systems that could be addressed to promote a positive school experience.

This dissertation concludes with considerations of how narrative approaches can be used to guide the work of Educational Psychologists. Implications for professional practice have been shared, highlighting the importance of viewing the needs of young people with ME/CFS holistically, and adopting a person-centred approach.

Source: Lewis, Mariana L. A narrative inquiry into the school experiences of teenagers living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Educational Psychology Thesis (DEdPsy). University of Bristol. https://research-information.bris.ac.uk/ws/portalfiles/portal/349168131/Final_Copy_2022_12_06_Lewis_M_L_DEdPsy.pdf (Full text)