Tag: covid-19

Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study

Abstract:

The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety (“physio-affective”) symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways.

This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores.

Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID.

In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity.

Source: Hussein Kadhem Al-Hakeim, Haneen Tahseen Al-Rubaye, Dhurgham Shihab Al-Hadrawi, Abbas F. Almulla, Michael Maes. Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study. medRxiv 2022.04.25.22274251; doi: https://doi.org/10.1101/2022.04.25.22274251 https://www.medrxiv.org/content/10.1101/2022.04.25.22274251v1.full-text  (Full text)

SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Abstract:

There is strong evidence for brain-related abnormalities in COVID-19 1-13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects.

We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

Source: Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. medRxiv [Preprint]. 2022 Mar 2:2021.06.11.21258690. doi: 10.1101/2021.06.11.21258690. Update in: Nature. 2022 Mar 7;: PMID: 34189535; PMCID: PMC8240690. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046077/ (Full text)

Long COVID Citizen Scientists: Developing a Needs-Based Research Agenda by Persons Affected by Long COVID

Abstract:

Background: Long-term health consequences following acute SARS-CoV-2 infection, referred to as post-COVID-19 condition or Long COVID, are increasing, with population-based prevalence estimates for adults at around 20%. Persons affected by Long COVID report various health problems, yet evidence to guide clinical decision making remains scarce.

Objective: The present study aimed to identify Long COVID research priorities using a citizen science approach and solely considering the needs of those affected.

Methods: This citizen science study followed an iterative process of patient needs identification, evaluation and prioritisation. A Long COVID Citizen Science Board (21 persons with Long COVID, and seven with myalgic encephalomyelitis/chronic fatigue syndrome) and a Long COVID Working Group (25 persons with Long COVID, four patients with myalgic encephalomyelitis/chronic fatigue syndrome and one relative) were formed. The study included four activities: three remote meetings and one online survey. First, Board members identified the needs and research questions. Second, Working Group members and persons affected by Long COVID (241 respondents, 85.5% with Long COVID, 14.5% with myalgic encephalomyelitis/chronic fatigue syndrome and 7.1% relatives) evaluated the research questions on a 1-5 Likert scale using an online survey. Then the Board gave feedback on this evaluation. Finally, Board members set the priorities for research through voting and discussion.

Results: Sixty-eight research questions were generated by the Board and categorised into four research domains (medicine, healthcare services, socioeconomics and burden of disease) and 14 subcategories. Their average importance ratings were moderate to high and varied from 3.41 (standard deviation = 1.16) for sex-specific diagnostics to 4.86 (standard deviation = 0.41) for medical questions on treatment. Five topics were prioritised: “treatment, rehabilitation and chronic care management”, “availability of interfaces for treatment continuity”, “availability of healthcare structures”, “awareness and knowledge among professionals” and “prevalence of Long COVID in children and adolescents”.

Conclusions: To our knowledge, this is the first study developing a citizen-driven, explicitly patient-centred research agenda with persons affected by Long COVID, setting it apart from existing multi-stakeholder efforts. The identified priorities could guide future research and funding allocation. Our methodology establishes a framework for citizen-driven research agendas, suitable for transfer to other diseases.

Source: Ziegler S, Raineri A, Nittas V, Rangelov N, Vollrath F, Britt C, Puhan MA. Long COVID Citizen Scientists: Developing a Needs-Based Research Agenda by Persons Affected by Long COVID. Patient. 2022 Apr 28. doi: 10.1007/s40271-022-00579-7. Epub ahead of print. PMID: 35478078. https://link.springer.com/article/10.1007/s40271-022-00579-7 (Full text)

The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome

Abstract:

Introduction: This study aimed to evaluate chronic pain and fatigue in patients 12 months after hospitalization for Covid-19.

Methods: We studied the COVID-19 patients discharged from Hospital, March 10 and April 20, 2020.

Results: A total of 157 patients were included in this study. Forty-three patients (27.4%) complained of chronic fatigue and muscle weakness in the last six months. The visual analog fatigue scale (VAFS) score of 3.84 ± 1.48 was obtained. Forty patients (25.5%) were suspected of Chronic Fatigue Syndrome (CFS).Twenty-four patients (15.3%) had severe chronic pain or exacerbation of previous chronic pain, most of which were reported in the lower back (70.8%) and lower extremities (66.7%). Pain intensity had a mean score of 2.33 ± 0.87 and was mainly described as “muscle cramps,” “persistent dull pain,” and “boring and numbing.” In women, chronic pain and fatigue, extended hospital stays, ICU admission, and depressed mood were common than in men.For these pain and fatigue, 37% used nonsteroidal anti-inflammatory drugs, and 16.3% used antidepressants. Only one person had applied for physiotherapy, and none of the patients had received psychotherapy.

Conclusion: Fatigue and chronic pain in patients recovering from COVID-19 are common complications, even after 12 months of illness.

Source: Janbazi L, Kazemian A, Mansouri K, Madani SP, Yousefi N, Vahedifard F, Raissi G. The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome. Am J Phys Med Rehabil. 2022 Apr 13. doi: 10.1097/PHM.0000000000002030. Epub ahead of print. PMID: 35473921.  https://pubmed.ncbi.nlm.nih.gov/35473921/

Frailty assessment for COVID-19 follow-up: a prospective cohort study

Abstract:

Background: The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19.

Objectives: To investigate frailty and the CFS for post-COVID-19 follow-up.

Methods: This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively.

Results: Of the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2-3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=-0.48, p<0.001) (criterion validity) and with the St George’s Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=-0.25, p<0.001), 6 min walk distance (r=-0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02).

Conclusions: The CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly.

Source: Müller I, Mancinetti M, Renner A, Bridevaux PO, Brutsche MH, Clarenbach C, Garzoni C, Lenoir A, Naccini B, Ott S, Piquilloud L, Prella M, Que YA, Soccal PM, von Garnier C, Geiser TK, Funke-Chambour M, Guler S. Frailty assessment for COVID-19 follow-up: a prospective cohort study. BMJ Open Respir Res. 2022 Apr;9(1):e001227. doi: 10.1136/bmjresp-2022-001227. PMID: 35459694. https://bmjopenrespres.bmj.com/content/9/1/e001227.long (Full text)

Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review

Abstract:

Introduction: This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis.

Methods: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection.

Results: 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia- 0.51 (95% CI: 0.37,0.65), Europe- 0.44 (95% CI: 0.32,0.56), and North America- 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]).

Discussion: This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

Source: Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022 Apr 16:jiac136. doi: 10.1093/infdis/jiac136. Epub ahead of print. PMID: 35429399. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac136/6569364?login=false (Full text available as PDF file)

Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features

Abstract:

Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed “post-COVID-19 syndrome” or “long COVID”. Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments.

Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.

Source: Mohamed MS, Johansson A, Jonsson J, Schiöth HB. Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features. Int J Mol Sci. 2022 Apr 12;23(8):4275. doi: 10.3390/ijms23084275. PMID: 35457093. https://www.mdpi.com/1422-0067/23/8/4275/htm (Full text)

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study

Abstract:

The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs).
Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05).
Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.
Source: Wright J, Astill SL, Sivan M. The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study. International Journal of Environmental Research and Public Health. 2022; 19(9):5093. https://doi.org/10.3390/ijerph19095093  https://www.mdpi.com/1660-4601/19/9/5093/htm (Full text)

A systematic review on physical function, activities of daily living and health-related quality of life in COVID-19 survivors

Abstract:

Objective: To analyze the published studies that investigated the physical function, activities of daily living and health-related quality of life in COVID-19 survivors.

Design: Systematic review.

Methods: We searched MEDLINE/PubMed, Scopus, SciELO, and Cochrane Library for studies that evaluated the physical function, activities of daily living and health-related quality of life after COVID-19 from the earliest date available to July 2021. Two independent reviewers screened and selected the studies. The Newcastle Ottawa Scale was used to evaluate methodological quality.

Results: We included 35 studies in this systematic review. Of the 35 studies included, 28 were cohort, and 7 cross-sectional studies The studies demonstrated that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Furthermore, incomplete recovery of physical function, and performance in activities of daily living were observed 1 to 6 months post-infection.

Discussion: Physical disability and reduction in health-related quality of life is a common condition in post-COVID-19 and impairments may persist up to 1 to 6 months. Researchers and clinicians can use these findings to understand the potential disabilities and rehabilitation needs of people recovering from the COVID-19.

Source: de Oliveira Almeida K, Nogueira Alves IG, de Queiroz RS, de Castro MR, Gomes VA, Santos Fontoura FC, Brites C, Neto MG. A systematic review on physical function, activities of daily living and health-related quality of life in COVID-19 survivors. Chronic Illn. 2022 Apr 11:17423953221089309. doi: 10.1177/17423953221089309. Epub ahead of print. PMID: 35404175; PMCID: PMC9006095. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006095/ (Full text)

Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study

Abstract:

Background: Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology.

Methods: Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue.

Results: Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003).

Conclusions: Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561.

Source: Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, Gordin Y, Agmon H, Epstein NK, Atamna A, Tishler O, Daitch V, Babich T, Abecasis D, Yarom Y, Kazum S, Shitenberg D, Baltaxe E, Elkana O, Shapira-Lichter I, Leibovici L, Yahav D. Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. 2022 Apr 11:ciac283. doi: 10.1093/cid/ciac283. Epub ahead of print. PMID: 35403679.  https://pubmed.ncbi.nlm.nih.gov/35403679/