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Tag: 2022

Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery

Abstract:

Background: Lingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gut tissue might be a source of infection during bariatric surgery. This study aimed to confirm the presence of SARS-CoV-2 nucleocapsid in gastric and gallbladder tissues removed during bariatric surgery in individuals previously infected with coronavirus disease 2019 (COVID-19) who had negative polymerase chain reaction results prior to the surgery.

Methods: Gastric and gallbladder specimens from 80 patients who underwent bariatric surgery between November 2021 and May 2022 and had a history of COVID-19 infection with gastrointestinal symptoms were examined for the presence of lingering SARS-CoV-2 nucleocapsid proteins using immunohistochemistry.

Results: Gastric specimens from 26 (32.5%) patients and 4 (100%) cholecystectomy specimens showed positive cytoplasmic staining for the anti-SARS-CoV-2 nucleocapsid protein in surface mucosal epithelial cells. The mean age was 37.8 ± 10.3 years. The average body mass index was 44.2 ± 7.0 kg/m2; most of the patients were females (71.3%). The positive staining group was significantly younger than the negative staining group (p = 0.007). The full-dose vaccination rate was 58.8%, with a median of 91 days after the last vaccine dose. A positive serological anti-spike IgG response was observed in 99% of the patients. The median time between initial COVID-19 infection and surgery was 274 and 380 days in the positive and negative staining groups, respectively (p = 0.371).

Conclusion: Gastric and gallbladder tissues can retain SARS-CoV-2 particles for a long time after COVID-19 infection, handling stomach specimens from patients during an operation must be done with care, as we usually do, but now with the knowledge that in 1/3 of patients they can be present. Performing LSG on post-COVID patients did not seem to increase perioperative morbidity.

Source: Hany, M., Zidan, A., Gaballa, M. et al. Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery. OBES SURG (2022). https://doi.org/10.1007/s11695-022-06338-9  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628579/ (Full text)

Long COVID: long-term health outcomes and implications for policy and research

Long COVID, which refers to post-acute and chronic sequelae of SARS-CoV-2 infection, can affect nearly every organ system and all demographic groups. The high and growing toll of long COVID calls for an urgent need to understand how to prevent and treat it. Governments and health systems must address the care needs of people with long COVID.

Shortly after the beginning of the COVID-19 global pandemic, reports emerged showing that some individuals infected with SARS-CoV-2 developed persistent symptoms and new health problems that arose long after the acute phase of infection and could not be explained by other factors1. The patient community who, to their credit, first recognized and reported this new syndrome used the term ‘long COVID’ to describe the post-acute and chronic sequelae of SARS-CoV-2 infection1. Long COVID can affect people across the lifespan — children, young adults and older adults — and across sex, race and ethnicity, and baseline health status2. Importantly, this syndrome not only affects patients who had severe COVID-19, but is also observed in individuals who were asymptomatic or mildly symptomatic during the acute phase of SARS-CoV-2 infection.

Read the rest of this article HERE. 

Source: Al-Aly, Z., Agarwal, A., Alwan, N. et al. Long COVID: long-term health outcomes and implications for policy and research. Nat Rev Nephrol (2022). https://doi.org/10.1038/s41581-022-00652-2  (Full text)

The autoimmune aetiology of unexplained chronic pain

Abstract:

Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as ‘chronic primary pains’ (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, ‘nociplasticic pain’ has been developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system.

Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pain associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble those of the clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the molecular and cellular details.

The central nervous system appears largely unaffected by antibody binding, suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream of peripheral processes. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms.

Source: Goebel A, Andersson D, Helyes Z, Clark JD, Dulake D, Svensson C. The autoimmune aetiology of unexplained chronic pain. Autoimmun Rev. 2022 Mar;21(3):103015. doi: 10.1016/j.autrev.2021.103015. Epub 2021 Dec 10. PMID: 34902604. https://www.sciencedirect.com/science/article/abs/pii/S1568997221002974 (Full text)

Doctors’ attitudes toward specific medical conditions

Abstract:

This study uses machine learning and natural language processing tools to examine the language used by healthcare professionals on a global online forum. It contributes to an underdeveloped area of knowledge, that of physician attitudes toward their patients. Using comments left by physicians on Reddit’s ”Medicine” subreddit (r/medicine), we test if the language from online discussions can reveal doctors’ attitudes toward specific medical conditions. We focus on a set of chronic conditions that usually are more stigmatized and compare them to ones well accepted by the medical community.

We discovered that when comparing diseases with similar traits, doctors discussed some conditions with more negative attitudes. These results show bias does not occur only along the dimensions traditionally analyzed in the economics literature of gender and race, but also along the dimension of disease type. This is meaningful because the emotions associated with beliefs impact physicians’ decision making, prescribing behavior, and quality of care. First, we run a binomial LASSO-logistic regression to compare a range of 21 diseases against myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), depression, and the autoimmune diseases multiple sclerosis and rheumatoid arthritis.

Next, we use dictionary methods to compare five more chronic diseases: Lyme disease, Ehlers-Danlos syndrome (EDS), Alzheimer’s disease, osteoporosis, and lupus. The results show physicians discuss ME/CFS, depression, and Lyme disease with more negative language than the other diseases in the set. The results for ME/CFS included over four times more negative words than the results for depression.

Source: Brooke Scoles, Catia Nicodemo. Doctors’ attitudes toward specific medical conditions. Journal of Economic Behavior & Organization, Volume 204, December 2022, Pages 182-199. https://www.sciencedirect.com/science/article/pii/S016726812200347X (Full text)

Prevalence and Correlates of Long COVID Symptoms Among US Adults

Abstract:

Importance: Persistence of COVID-19 symptoms beyond 2 months, or long COVID, is increasingly recognized as a common sequela of acute infection.

Objectives: To estimate the prevalence of and sociodemographic factors associated with long COVID and to identify whether the predominant variant at the time of infection and prior vaccination status are associated with differential risk.

Design, setting, and participants: This cross-sectional study comprised 8 waves of a nonprobability internet survey conducted between February 5, 2021, and July 6, 2022, among individuals aged 18 years or older, inclusive of all 50 states and the District of Columbia.

Main outcomes and measures: Long COVID, defined as reporting continued COVID-19 symptoms beyond 2 months after the initial month of symptoms, among individuals with self-reported positive results of a polymerase chain reaction test or antigen test.

Results: The 16 091 survey respondents reporting test-confirmed COVID-19 illness at least 2 months prior had a mean age of 40.5 (15.2) years; 10 075 (62.6%) were women, and 6016 (37.4%) were men; 817 (5.1%) were Asian, 1826 (11.3%) were Black, 1546 (9.6%) were Hispanic, and 11 425 (71.0%) were White. From this cohort, 2359 individuals (14.7%) reported continued COVID-19 symptoms more than 2 months after acute illness. Reweighted to reflect national sociodemographic distributions, these individuals represented 13.9% of those who had tested positive for COVID-19, or 1.7% of US adults. In logistic regression models, older age per decade above 40 years (adjusted odds ratio [OR], 1.15; 95% CI, 1.12-1.19) and female gender (adjusted OR, 1.91; 95% CI, 1.73-2.13) were associated with greater risk of persistence of long COVID; individuals with a graduate education vs high school or less (adjusted OR, 0.67; 95% CI, 0.56-0.79) and urban vs rural residence (adjusted OR, 0.74; 95% CI, 0.64-0.86) were less likely to report persistence of long COVID. Compared with ancestral COVID-19, infection during periods when the Epsilon variant (OR, 0.81; 95% CI, 0.69-0.95) or the Omicron variant (OR, 0.77; 95% CI, 0.64-0.92) predominated in the US was associated with diminished likelihood of long COVID. Completion of the primary vaccine series prior to acute illness was associated with diminished risk for long COVID (OR, 0.72; 95% CI, 0.60-0.86).

Conclusions and relevance: This study suggests that long COVID is prevalent and associated with female gender and older age, while risk may be diminished by completion of primary vaccination series prior to infection.

Source: Perlis RH, Santillana M, Ognyanova K, Safarpour A, Lunz Trujillo K, Simonson MD, Green J, Quintana A, Druckman J, Baum MA, Lazer D. Prevalence and Correlates of Long COVID Symptoms Among US Adults. JAMA Netw Open. 2022 Oct 3;5(10):e2238804. doi: 10.1001/jamanetworkopen.2022.38804. PMID: 36301542.  https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797782 (Full text)

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.

Methods: In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.

Results: Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).

Conclusions: Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Source: Wang Z, Waldman MF, Basavanhally TJ, Jacobs AR, Lopez G, Perichon RY, Ma JJ, Mackenzie EM, Healy JB, Wang Y, Hersey SA. Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome. J Transl Med. 2022 Oct 25;20(1):486. doi: 10.1186/s12967-022-03682-3. PMID: 36284352; PMCID: PMC9592873.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592873/ (Full study)

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”, which is a dramatic increase in inflammatory cytokines in the blood.
In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or “Long COVID”. Therefore, there is an urgent need to better understand the mechanisms of the virus.
The spike protein on the surface of the virus is composed of joined S1–S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm.
In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.
Source: Forsyth CB, Zhang L, Bhushan A, Swanson B, Zhang L, Mamede JI, Voigt RM, Shaikh M, Engen PA, Keshavarzian A. The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells. Microorganisms. 2022; 10(10):1996. https://doi.org/10.3390/microorganisms10101996 https://www.mdpi.com/2076-2607/10/10/1996/htm (Full text)

Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia

Abstract:

Background: Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM.

Methods: A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β).

Results: COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients.

Discussion: Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.

Source: Polli A, Hendrix J, Ickmans K, Bakusic J, Ghosh M, Monteyne D, Velkeniers B, Bekaert B, Nijs J, Godderis L. Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia. J Transl Med. 2022 Oct 25;20(1):487. doi: 10.1186/s12967-022-03662-7. PMID: 36284330; PMCID: PMC9598022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598022/ (Full text)

Combination of whole-body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome

Abstract:

Background: The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population.

Methods: Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total.

Results: A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function.

Conclusions: Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.

Source: Kujawski S, Słomko J, Godlewska BR, Cudnoch-Jędrzejewska A, Murovska M, Newton JL, Sokołowski Ł, Zalewski P. Combination of whole body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome. J Transl Med. 2022 Jun 17;20(1):273. doi: 10.1186/s12967-022-03460-1. PMID: 35715857; PMCID: PMC9204866.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204866/ (Full text)

Beyond COVID-19 and SARS-CoV-2, cardiovascular outcomes of “long covid” from a pathological perspective – a look back and road ahead

Abstract:

With the decrease in severity of COVID-19 there is a sense of relief in the general population. However, there has been an increased incidence of cardiovascular and other organ complications post-infection, which have raised concerns about long COVID. The term “long COVID” was first used by Perego on social media to denote the persistence of symptoms weeks or months after initial SARS-CoV-2 infection and the term ‘long haulers’ was first described by Watson and by Yong to identify post-COVID conditions.

There has been an increased incidence of sudden cardiac death and MI post-COVID-19 in healthy individuals, sports persons and prominent movie stars. Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 may include 1) Damage to tissues and cells that are important for blood flow, so clotting of blood is increased. 2) Persistence of fragments of virus or its sub-particles/ protein material in a wide range of body sites and, 3) an immune system gone haywire.

As the majority of countries across the globe are easing coronavirus precautionary measures, there is an urgent need by health care organizations and policymakers worldwide to generate awareness by educating the public at large, about the ill effects of long-COVID and varied types of post-acute sequelae of COVID-19.

Source: Aden D, Zaheer S, Kumar R, Raj S, Khan T, Varshney S. Beyond COVID-19 and SARS-CoV-2, cardiovascular outcomes of “long covid” from a pathological perspective – a look back and road ahead. Pathol Res Pract. 2022 Sep 29;239:154144. doi: 10.1016/j.prp.2022.154144. Epub ahead of print. PMID: 36242969; PMCID: PMC9519512.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519512/ (Full text)