Tag: 2022

Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study

Abstract:

Objective: Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms.

Patients and methods: A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest.

Results: The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups.

Conclusions: Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.

Source: Mohamed Hussein AAR, Galal I, Amin MT, Moshnib AA, Makhlouf NA, Makhlouf HA, Abd-Elaal HK, Kholief KMS, Abdel Tawab DA, Kamal Eldin KA, Attia AM, Othman AEA, Shah J, Aiash H. Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study. Eur Rev Med Pharmacol Sci. 2022 Apr;26(8):3038-3045. doi: 10.26355/eurrev_202204_28635. PMID: 35503606. https://www.europeanreview.org/article/28635 (Full text)

Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician

Abstract:

Purpose of review: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.

Recent findings: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.

Source: Tobler DL, Pruzansky AJ, Naderi S, Ambrosy AP, Slade JJ. Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician. Curr Atheroscler Rep. 2022 May 4:1–8. doi: 10.1007/s11883-022-01032-8. Epub ahead of print. PMID: 35507278; PMCID: PMC9065238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065238/ (Full text)

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

Abstract:

in English, Portuguese

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified.

(Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Source: Baldi BG, Fabro AT, Franco AC, Machado MHC, Prudente RA, Franco ET, Marrone SR, Vale SAD, Cezare TJ, Moraes MPT, Ferreira EVM, Albuquerque ALP, Sawamura MVY, Tanni SE. Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series. J Bras Pneumol. 2022 Apr 29;48(3):e20210438. doi: 10.36416/1806-3756/e20210438. PMID: 35508067; PMCID: PMC9064656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064656/  (Full text)

Post-acute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases

Abstract:

Background and aims: The coronavirus disease 2019 (COVID-19) pandemic affects populations, societies and lives for more than two years. Long-term sequelae of COVID-19, collectively termed the post-acute COVID-19 syndrome, are rapidly emerging across the globe. Here, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen persistence underlies the post-acute COVID-19 syndrome.

Methods: We performed an endoscopy study with 46 inflammatory bowel disease (IBD) patients 219 days (range: 94-257) after a confirmed COVID-19 infection. SARS-CoV-2 antigen persistence was assessed in the small and large intestine by qPCR of four viral transcripts, immunofluorescence of viral nucleocapsid and virus cultivation from biopsy tissue. Post-acute COVID-19 was assessed by a standardized questionnaire, and a systemic SARS-CoV-2 immune response was evaluated by flow-cytometry and ELISA at endoscopy. IBD activity was evaluated by clinical, biochemical and endoscopic means.

Results: We report expression of SARS-CoV-2 RNA in the gut mucosa ∼7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8+ T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19, immunosuppressive therapy and gut inflammation. We were unable to culture SARS-CoV-2 from gut tissue of patients with viral antigen persistence. Post-acute sequelae of COVID-19 were reported from the majority of patients with viral antigen persistence, but not from patients without viral antigen persistence.

Conclusion: Our results indicate that SARS-CoV-2 antigen persistence in infected tissues serves as a basis for post-acute COVID-19. The concept that viral antigen persistence instigates immune perturbation and post-acute COVID-19 requires validation in controlled clinical trials.

Source: Zollner A, Koch R, Jukic A, Pfister A, Meyer M, Rössler A, Kimpel J, Adolph TE, Tilg H. Post-acute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases. Gastroenterology. 2022 Apr 28:S0016-5085(22)00450-4. doi: 10.1053/j.gastro.2022.04.037. Epub ahead of print. PMID: 35508284; PMCID: PMC9057012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057012/ (Full text)

Long COVID and neuropsychiatric manifestations (Review)

Abstract:

There is accumulating evidence in the literature indicating that a number of patients with coronavirus disease 2019 (COVID-19) may experience a range of neuropsychiatric symptoms, persisting or even presenting following the resolution of acute COVID-19. Among the neuropsychiatric manifestations more frequently associated with ‘long COVID’ are depression, anxiety, post-traumatic stress disorder, sleep disturbances, fatigue and cognitive deficits, that can potentially be debilitating and negatively affect patients’ wellbeing, albeit in the majority of cases symptoms tend to improve over time.

Despite variations in results obtained from studies using different methodological approaches to define ‘long COVID’ syndrome, the most widely accepted factors associated with a higher risk of developing neuropsychiatric manifestations include the severity of foregoing COVID-19, the female sex, the presence of comorbidities, a history of mental health disease and an elevation in the levels of inflammatory markers, albeit further research is required to establish causal associations. To date, the pathophysiological mechanisms implicated in neuropsychiatric manifestations of ‘long COVID’ remain only partially elucidated, while the role of the indirect effects of the COVID-19 pandemic, such as social isolation and uncertainty concerning social, financial and health recovery post-COVID, have also been highlighted.

Given the alarming effects of ‘long-COVID’, interdisciplinary cooperation for the early identification of patients who are at a high risk of persistent neuropsychiatric presentations, beyond COVID-19 recovery, is crucial to ensure that appropriate integrated physical and mental health support is provided, with the aim of mitigating the risks of long-term disability at a societal and individual level.

Source: Efstathiou V, Stefanou MI, Demetriou M, Siafakas N, Makris M, Tsivgoulis G, Zoumpourlis V, Kympouropoulos SP, Tsoporis JN, Spandidos DA, Smyrnis N, Rizos E. Long COVID and neuropsychiatric manifestations (Review). Exp Ther Med. 2022 May;23(5):363. doi: 10.3892/etm.2022.11290. Epub 2022 Apr 1. PMID: 35493431; PMCID: PMC9019760. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019760/ (Full text)

The long-COVID-19 in older adults: facts and conjectures

The coronavirus disease-19 (COVID-19) has greatly affected the overall health of the elderly population through direct biological (infection-related) and indirect psychosocial (quarantine- and isolation-related) effects. Because the severe form of COVID-19 most frequently targets this population, the prevalence of long-term sequelae is expected to rise consequentially in people ≥ 65 years old. The prominent neuropsychiatric consequences of COVID-19 and the cognitive frailty seen in older adults can both have a negative impact on their mental health.

To explore the behavioral, neurological, and psychosocial consequences of COVID-19, we conducted separate studies on different populations of older adult people residing in Lombardy – the Italian epicenter of the first pandemic wave in spring 2020. In one study, we found that behavioral changes (i.e., delirium) were a frequent symptom of COVID-19, manifesting at disease onset and preceding the typical symptoms in about 1/3 (36.8%) of cases, particularly in patients with neurocognitive disorders (NCD), such as dementia (major-NCD) or mild cognitive impairment (mild-NCD). Delirium was also associated with short-term mortality and potential long-term cognitive sequelae (Poloni et al., 2020).

To uncover the neuropathology underlying behavioral changes and their possible effects over time, we compared 9 brains of elderly patients who had died of COVID-19 (with and without dementia) with 6 brains from age-matched non-COVID controls. The main finding was an excessive innate immune response, represented by microglial hyperactivation. Although we observed severe inflammatory changes especially in the brainstem, we did not find neuropathological evidence suggestive of SARS-CoV-2 replication in the brain (Gagliardi et al., 2021; Poloni et al., 2021).

In a study evaluating the psychosocial consequences of the lockdown due to the pandemic (Carlos et al., 2021), we observed that those with mild-moderate dementia were unable to cope and adapt to the life changes caused by the restrictions and consequently suffered from depression and cognitive decline. Before COVID, patients with dementia normally engaged in habitual daily activities. The disruption of said routines, the inability to engage in new activities, and the incapability to use modern technologies all triggered psychological distress and some degree of cognitive and motor regression (Figure 1A). Although lockdown (the sternest form of quarantine in history) protected them from COVID-19, the social seclusion and the inability to access primary care treatment – aggravated by an unprepared and unequipped primary care health sector – caused further complications (Carlos et al., 2021). Moreover, the general effects of the pandemic in terms of loss of “individual freedom”, economic crisis, and mass media conditioning should not be overlooked due to their possible impact on mental health.

Source: Poloni, Tino Emanuele; Medici, Valentina; Zito, Antonio; Carlos, Arenn Faye The long-COVID-19 in older adults, Neural Regeneration Research: December 2022 – Volume 17 – Issue 12 – p 2679-2681 doi: 10.4103/1673-5374.339483 https://journals.lww.com/nrronline/Fulltext/2022/12000/The_long_COVID_19_in_older_adults__facts_and.27.aspx (Full text)

Development of a Mouse Model for Chronic Fatigue Syndrome

Abstract:

The purpose of this study was to develop a clinically relevant mouse model of CFS to allow for the testing of underlying mechanisms and development of novel treatment interventions.

Mice were injected with either lipopolysaccharide (LPS) or Poly I:C systemically (0.1- 1.0 mg/kg LPS, i.p. or 0.6-6mg/kg Poly I:C) and compared to a vehicle control injection.

To test for fatigue-like behaviors, we examined voluntary wheel running (VWR) and open field activity.

To test for pain-like behaviors, muscle withdrawal thresholds (MWT) and mechanical sensitivity of the paw.

Measurements were assessed before and up to 1 week after injection of LPS or Poly I:C.

Differences in voluntary running wheel data were assessed using mixed model analysis for differences between dose, time and an interaction between dose and time.

Differences in open field parameters, MWT, and paw sensitivity between groups were assessed using repeated measures ANOVAs.

Running wheel activity was reduced after injection of either LPS or Poly I:C (χ2=15.4; p=0.003).

LPS reduced running wheel activity on days 1-3 for the 1.0 mg/kg dose of LPS and on Day 1 for Poly I:C when compared to vehicle (p<0.001).

Lower doses of LPS showed faster recovery to baseline.

For the open field testing, LPS reduced in distance travelled (F=9.1; p<0.001), increase in time standing still (F=6.5, p=0.001) but not time in center (F= 1.1, p=0.36) 24h after infection.

Post-hoc testing (Tukey’s test) showed a significant difference between the vehicle and the 1.0 mg/kg group of LPS (p=0.001).

Similar reductions were observed for the 6 mg/kg group of Poly I:C (p<0.001). For pain behaviors, there was no difference between groups in the MWT or paw sensitivity (p>0.05) for either LPS or Poly I:C.

These results show that a single injection of an infectious agent reduces physical activity and exploratory behavior, but does not produce pain behaviors.

Source: Adam Janowski, Joseph Lesnak, Ashley Plumb, Lynn Rasmussen, Kathleen Sluka. Development of a Mouse Model for Chronic Fatigue Syndrome. The Journal of Pain 23 (5): 12. https://www.sciencedirect.com/science/article/abs/pii/S152659002200092X

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

Abstract:

There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers.

The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network.

We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which were established in CFAS-D patients.

PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks.

MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA.

The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease.

Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus.

In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

Source: Michael Maes, Marta Kubera and Magdalena Kotańska. Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Frontiers in Psychiatry 13: 822382. https://www.frontiersin.org/articles/10.3389/fpsyt.2022.822382/full  (Full text)

Breast Implant-Associated Immunological Disorders

Abstract:

Background: Breast implants are commonly placed postbreast cancer reconstruction, cosmetic augmentation, and gender-affirming surgery. Breast implant illness (BII) is a systemic complication associated with breast implants. Patients with BII may experience autoimmune symptoms including fatigue, difficulty concentrating, hair loss, weight change, and depression. BII is poorly understood, and the etiology is unknown. The purpose of this literature review is to characterize BII autoimmune disorders and determine possible causes for its etiology.

Methods: The PubMed, Google Scholar, Embase, Web of Science, and OVID databases were interrogated from 2010 to 2020 using a query strategy including search term combinations of “implants,” “breast implant illness,” “autoimmune,” and “systemic illness.”

Results: BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. A review of epidemiological studies in the past ten years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren’s syndrome, rheumatoid arthritis, systemic sclerosis, chronic fatigue syndrome, and Raynaud’s syndrome. Explantation resulted in alleviation of symptoms in over 50% of patients, strengthening the hypothesis linking breast implants to BII. Studies have shown that silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem.

Conclusion: BII could be dependent on biofilm infection and the microenvironment around the implants. The true pathophysiology behind these complaints must be further investigated so that alternative treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.

Source: Suh LJ, Khan I, Kelley-Patteson C, Mohan G, Hassanein AH, Sinha M. Breast Implant-Associated Immunological Disorders. J Immunol Res. 2022 May 4;2022:8536149. doi: 10.1155/2022/8536149. PMID: 35571560; PMCID: PMC9095406. https://pubmed.ncbi.nlm.nih.gov/35571560/

Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Objectives: Studies have demonstrated immune dysfunction in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); however, evidence is varied. The current study used network analysis to examine relationships between cytokines among a sample of pediatric participants with ME/CFS.

Methods: 10,119 youth aged 5-17 in the Chicagoland area were screened for ME/CFS; 111 subjects and controls were brought in for a physician examination and completed a blood draw. Youth were classified as controls (Cs, N = 43), ME/CFS (N = 23) or severe (S-ME/CFS, N = 45). Patterns of plasma cytokine networks were analyzed.

Results: All participant groups displayed a primary network of interconnected cytokines. In the ME/CFS group, inflammatory cytokines IL-12p70, IL-17A, and IFN-γ were connected and included in the primary membership, suggesting activation of inflammatory mechanisms. The S-ME/CFS group demonstrated a strong relationship between IL-17A and IL-23, a connection associated with chronic inflammation. The relationships of IL-6 and IL-8 in ME/CFS and S-ME/CFS participants also differed from Cs. Together, these results indicate pro-inflammatory responses in our illness populations.

Discussion: Our data imply biological differences between our three participant groups, with ME/CFS and S-ME/CFS participants demonstrating an inflammatory profile. Examining co-expression of cytokines may aid in the identification of a biomarker for pediatric ME/CFS.

Source: Jason LA, Gaglio CL, Furst J, Islam M, Sorenson M, Conroy KE, Katz BZ. Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Chronic Illn. 2022 May 16:17423953221101606. doi: 10.1177/17423953221101606. Epub ahead of print. PMID: 35570777.  https://pubmed.ncbi.nlm.nih.gov/35570777/