Tag: long Covid

The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus.

There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients.

This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.

Source: WALKER, Max Oliver Mackay et al. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3050>. Date accessed: 09 oct. 2022. doi: https://doi.org/10.18103/mra.v10i9.3050.

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program

Abstract:

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations. Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design, Settings, and Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination.

Main Outcomes and Measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards.

Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).

Conclusions and Relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.

Source: M Daniel Brannock, Robert F Chew, Alexander J Preiss, Emily C Hadley, Julie A McMurry, Peter J Leese, Andrew T Girvin, Miles Crosskey, Andrea G Zhou, Richard A Moffitt, Michele Jonsson Funk, Emily Pfaff, Melissa Haendel, Christopher G Chute, N3C Consortium, RECOVER Consortium. Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program. medRxiv 2022.10.06.22280795; doi: https://doi.org/10.1101/2022.10.06.22280795 (Full text available as PDF file)

Rehabilitation in long COVID-19: A mini-review

Abstract:

We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of ‘new normal’. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.

Source: Swarnakar R, Yadav SL. Rehabilitation in long COVID-19: A mini-review. World J Methodol. 2022 Jul 20;12(4):235-245. doi: 10.5662/wjm.v12.i4.235. PMID: 36159093; PMCID: PMC9350732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350732/ (Full text)

An international study of post-COVID sleep health

Abstract:

Objectives: COVID-19 has infected millions of people worldwide, with growing evidence that individuals with a history of infection may continue to show persistent post-COVID symptoms (long COVID). The aim of this study was to investigate sleep health in an international sample of individuals who reported previously testing positive for COVID-19.

Design: Cross-sectional.

Setting: Online survey distributed online between March and June 2021.

Participants: A total of 1001 individuals who reported a positive diagnosis of COVID-19 across different geographical regions, including North and South America, Sub-Saharan Africa, and Europe.

Measurements: Self-reported sleep health, using the Regulatory Satisfaction Alertness Timing Efficiency Duration scale, as recalled before a COVID-19 diagnosis and also reported currently.

Results: Individuals reported worse overall current sleep health, with lower ratings across the 6 dimensions of sleep health (sleep regularity, satisfaction, alertness, timing, efficiency, and duration) compared to their ratings as recalled before COVID-19 infection. Greater severity of COVID-19 symptoms was the strongest predictor of poor current sleep health (P < .001), independent of demographics, presence of a pre-existing chronic health condition, and time since infection. Poor current sleep health was associated with poorer current quality of life (P < .001).

Conclusions: Poor current sleep health is evident in individuals with a history of COVID-19, particularly those with more severe symptoms at the time of their COVID-19 infection and is associated with a poorer quality of life. Clinicians and researchers should assess sleep health in COVID-19 patients and investigate long-term associations with their mental and physical health, as well as potential benefits of improving sleep in this population.

Source: Alzueta E, Perrin PB, Yuksel D, Ramos-Usuga D, Kiss O, Iacovides S, de Zambotti M, Cortes M, Olabarrieta-Landa L, Arango-Lasprilla JC, Baker FC. An international study of post-COVID sleep health. Sleep Health. 2022 Sep 23:S2352-7218(22)00112-7. doi: 10.1016/j.sleh.2022.06.011. Epub ahead of print. PMID: 36163137; PMCID: PMC9501615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501615/ (Full text)

Post-COVID-19 Syndrome: A Novel Diagnosis

Abstract:

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Source: Kalia R, Kalia R, Musih J, Cubelo M, Popat J. Post-COVID-19 Syndrome: A Novel Diagnosis. Cureus. 2022 Aug 22;14(8):e28266. doi: 10.7759/cureus.28266. PMID: 36158335; PMCID: PMC9491485. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491485/ (Full text)

Long COVID symptoms in a population-based sample of persons discharged home from hospital

Abstract:

in English, French

Objectives: The impact of long COVID among persons hospitalized and discharged home is unknown. We aimed to (1) report the prevalence of long COVID in persons hospitalized for COVID-19 and discharged home; (2) estimate the prevalence of physical, sensory, and psychological/mental health impairments; and (3) explore associated factors.

Methods: We conducted a telephone survey of adult residents in Laval, Quebec, who were discharged home ≥ 2 months post-hospitalization for COVID-19. Participants responded to a standard questionnaire regarding persistent symptoms. We calculated the prevalence of long COVID and of persistent types of symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression.

Results: In our sample (n = 398), 70% reported physical symptoms, 58% psychological problems, and 16% sensory impairments. 31.5% reported being troubled by persistent symptoms (long COVID). Factors associated with long COVID were a greater number of symptoms (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.69-2.28) and increased hospital stay (OR = 1.03, 95% CI = 1.01-1.06). Other factors associated with physical and psychological symptoms were female sex (OR = 2.17, 95% CI = 1.27-3.71 and OR = 2.06, 95% CI = 1.25-3.39; respectively), higher education level (OR = 2.10, 95% CI = 1.20-3.68 and OR = 2.43, 95% CI = 1.44-4.14; respectively), and obesity (OR = 1.95, 95% CI = 1.15-3.34 and OR = 1.70, 95% CI = 1.05-2.77; respectively).

Conclusion: In this population-based study of persons hospitalized for COVID-19 and discharged home, nearly one third were troubled by symptoms for 2 months or more post-discharge. There was a high proportion with persistent physical and psychological/mental health symptoms. Further research will assess the specific needs of these patients to inform health policy makers on service requirements for these persons.

Source: Feldman DE, Boudrias MH, Mazer B. Long COVID symptoms in a population-based sample of persons discharged home from hospital. Can J Public Health. 2022 Sep 21:1–10. doi: 10.17269/s41997-022-00695-9. Epub ahead of print. PMID: 36131218; PMCID: PMC9491248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491248/ (Full text)

Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration

Abstract:

Through an adequate survey of the history of the disease, Narrative Medicine (NM) aims to allow the definition and implementation of an effective, appropriate, and shared treatment path. In the present study different topic modeling techniques are compared, as Latent Dirichlet Allocation (LDA) and topic modeling based on BERT transformer, to extract meaningful insights in the Italian narration of COVID-19 pandemic.

In particular, the main focus was the characterization of Post-acute Sequelae of COVID-19, (i.e., PASC) writings as opposed to writings by health professionals and general reflections on COVID-19, (i.e., non-PASC) writings, modeled as a semi-supervised task. The results show that the BERTopic-based approach outperforms the LDA-base approach by grouping in the same cluster the 97.26% of analyzed documents, and reaching an overall accuracy of 91.97%.

Source: Scarpino I, Zucco C, Vallelunga R, Luzza F, Cannataro M. Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration. BioTech (Basel). 2022 Sep 3;11(3):41. doi: 10.3390/biotech11030041. PMID: 36134915; PMCID: PMC9496775. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496775/ (Full text)

Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity?

Abstract:

Molecular mimicry between human and microbial/viral/parasite peptides is common and has long been associated with the etiology of autoimmune disorders provoked by exogenous pathogens. A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between the SARS-CoV-2 spike glycoprotein (S-protein) and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies.

A total of 14 pentapeptides shared by the SARS-CoV-2 S-protein, thyroid, pituitary, adrenal cortex autoantigens and beta-cells of the islets of Langerhans were identified, all of them belong to the immunoreactive epitopes of SARS-CoV-2. The discussion of the findings relates the results to the clinical correlates of COVID-19-associated autoimmune endocrinopathies. The most common of these illnesses is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to the marker autoantigens of this disease.

The most important in pathogenesis of severe COVID-19, according to the authors, may be autoimmunity against adrenals because their adequate response prevents excessive systemic action of the inflammatory mediators causing cytokine storm and hemodynamic shock. A critique of the antigenic mimicry concept is given with an assertion that peptide sharing is not a guarantee but only a prerequisite for provoking autoimmunity based on the molecular mimicry. The latter event occurs in carriers of certain HLA haplotypes and when a shared peptide is only used in antigen processing.

Source: Churilov LP, Normatov MG, Utekhin VJ. Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity? Pathophysiology. 2022 Aug 25;29(3):486-494. doi: 10.3390/pathophysiology29030039. PMID: 36136066; PMCID: PMC9504401. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504401/ (Full text)

Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms

Abstract:

Background: Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) were present up to a year after infection, and if they were associated with the development of clinically relevant Post-Acute Sequalae of COVID-19 (PASC) symptoms.

Methods: A rapid assessment line immunoassay was used to measure circulating levels of ANA/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6, and 12 months post-recovery. Patient-reported fatigue, cough, and dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines.

Results: Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, AUC=0.86) and dyspnea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1β had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months.

Interpretation: Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.

Source: Son K, Jamil R, Chowdhury A, Mukherjee M, Venegas C, Miyasaki K, Zhang K, Patel Z, Salter B, Yuen ACY, Lau KS, Cowbrough B, Radford K, Huang C, Kjarsgaard M, Dvorkin-Gheva A, Smith J, Li QZ, Waserman S, Ryerson CJ, Nair P, Ho T, Balakrishnan N, Nazy I, Bowdish DM, Svenningsen S, Carlsten C, Mukherjee M. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms. Eur Respir J. 2022 Sep 22:2200970. doi: 10.1183/13993003.00970-2022. Epub ahead of print. PMID: 36137590. https://pubmed.ncbi.nlm.nih.gov/36137590/

Neurological post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

The novel corona virus infectious disease, COVID-19, caused by SARS-CoV-2, can have two phases: acute (generally 4 weeks after onset) and chronic (> 4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID-19 are termed post-COVID condition, long COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC).

PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, sub-fever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization’s definition is quite broad. Consequently, it is difficult to correctly diagnose PASC.

Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID-19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC.

In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID-19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for PASC patients based on our outpatient clinic experience.

Source: Takao M, Ohira M. Neurological post-acute sequelae of SARS-CoV-2 infection (PASC). Psychiatry Clin Neurosci. 2022 Sep 23. doi: 10.1111/pcn.13481. Epub ahead of print. PMID: 36148558. https://pubmed.ncbi.nlm.nih.gov/36148558/