Category: Overlapping Illnesses

Inequity and disparities mar existing global research evidence on Long COVID

Abstract:

Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead.

With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.

Source: Taghrir MH, Akbarialiabad H, Abdollahi A, Ghahramani N, Bastani B, Paydar S, Razani B, Mwangi J, Asadi-Pooya AA, Roozbeh J, Malekmakan L, Kumar M. Inequity and disparities mar existing global research evidence on Long COVID. Glob Health Promot. 2022 Aug 12:17579759221113276. doi: 10.1177/17579759221113276. Epub ahead of print. PMID: 35962520. https://pubmed.ncbi.nlm.nih.gov/35962520/

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome

Abstract:

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them.

The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned.

Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Source: Mahroum N, Shoenfeld Y. Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome. Pathophysiology. 2022 Jul 28;29(3):414-425. doi: 10.3390/pathophysiology29030033. PMID: 35997389. https://www.mdpi.com/1873-149X/29/3/33/htm (Full text)

Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome

Abstract:

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms.

The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001).

To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.

Source: Barletta MA, Marino G, Spagnolo B, Bianchi FP, Falappone PCF, Spagnolo L, Gatti P. Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome. Clin Exp Med. 2022 Aug 22. doi: 10.1007/s10238-022-00871-8. Epub ahead of print. PMID: 35994177.  https://link.springer.com/article/10.1007/s10238-022-00871-8 (Full text)

Post COVID-19 condition of the Omicron variant of SARS-CoV-2

Abstract:

Objectives: To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains.

Study design: A single-center cross-sectional study.

Methods: Patients who recovered from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients’ characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching.

Results: We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively.

Conclusions: The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.

Source: Morioka S, Tsuzuki S, Suzuki M, Terada M, Akashi M, Osanai Y, Kuge C, Sanada M, Tanaka K, Maruki T, Takahashi K, Saito S, Hayakawa K, Teruya K, Hojo M, Ohmagari N. Post COVID-19 condition of the Omicron variant of SARS-CoV-2. J Infect Chemother. 2022 Aug 11:S1341-321X(22)00233-1. doi: 10.1016/j.jiac.2022.08.007. Epub ahead of print. PMID: 35963600; PMCID: PMC9365517. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365517/ (Full text)

The COVID-19 Pandemic and Post-Infection Irritable Bowel Syndrome: What Lies Ahead for Gastroenterologists

Clinical Problem

An increasingly recognized subset of patients develops post-infection sequelae also described as long COVID or postacute COVID-19 syndrome (PACS). These patients experience a myriad of neurologic, respiratory, cardiac, psychiatric, and/or GI symptoms that persist for 4 weeks or more from the initial diagnosis of SARS-CoV-2.

Epidemiology

In a survey study of 749 survivors, 29% reported at least 1 new chronic GI symptom 6 months after their COVID-19 infection, with heartburn, constipation, diarrhea, and abdominal pain being the most common.2 Of the patients with abdominal pain, 39% met Rome IV criteria for irritable bowel syndrome (IBS). Other studies also reported a 30%–40% prevalence of GI PACS. Additionally, COVID-19 infection was associated with worsening severity of preexisting IBS symptoms. Some risk factors for GI PACS include the presence of GI symptoms during acute infection, psychiatric diagnoses (depression, anxiety) both pre- and post-COVID-19, need for hospitalization during acute illness, and loss of smell and taste. Infectious gastroenteritis is an established risk-factor for development of disorders of gut-brain interaction (DGBI), particularly post-infection IBS (PI-IBS). Many of the risk factors for GI PACS described are also known predisposing factors for PI-IBS, with some exceptions, such as female gender, a risk factor for PI-IBS but not consistently associated with GI PACS. In addition to IBS, other de novo DGBIs, such as functional dyspepsia, heartburn, chest pain, and dysphagia, can be experienced in the spectrum of GI PACS.

Disease Mechanisms

The pathophysiology of PACS including that of the GI manifestations is incompletely understood; however, it is likely multifactorial (Figure 1). Epithelial invasion by SARS-CoV-2 is substantiated by the high expression levels of angiotensin-converting enzyme-2 on the enterocytes and colonocytes. The angiotensin-converting enzyme-2 is a negative regulator of the renin-angiotensin system and has a protective cellular role, including in the intestinal tract. Following the entry of SARS-CoV-2 in the cell, angiotensin-converting enzyme-2 protein is downregulated, resulting in an increase in angiotensin-II, the likely molecular mechanism of severe acute respiratory syndrome and systemic inflammatory response development with this coronavirus. Intestinal microbial dysbiosis has also been associated with acute SARS-CoV-2 infection and PACS. Long-term respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated lipopolysaccharide-binding protein levels. One study showed that dysbiosis in COVID-19 patients continued throughout their hospitalizations and up to 21 days from disease onset, with a decrease in health-promoting, short-chain fatty acid–forming bacteria.3 Gut microbiome of patients with PACS was characterized by higher levels of Ruminococcus gnavus and Bacteroides vulgatus, and lower levels of Faecalibacterium prausnitzii. Interestingly, presence of butyrate-producing bacteria showed an inverse correlation with development of PACS at 6 months.4 A recent study also suggested that salivary microbiome during acute infection may predict the development of GI PACS.5

Read the rest of this article HERE.

Source: Walter W. Chan and Madhusudan Grover. The COVID-19 Pandemic and Post-Infection Irritable Bowel Syndrome: What Lies Ahead for Gastroenterologists. Published: August 06, 2022. DOI: https://doi.org/10.1016/j.cgh.2022.05.044 (Full text)

Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design

Abstract:

Background: Chronic fatigue with a debilitating effect on daily life is a frequently reported symptom among adolescents and young adults with a history of Q-fever infection (QFS). Persisting fatigue after infection may have a biological origin with psychological and social factors contributing to the disease phenotype. This is consistent with the biopsychosocial framework, which considers fatigue to be the result of a complex interaction between biological, psychological, and social factors. In line, similar manifestations of chronic fatigue are observed in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and juvenile idiopathic arthritis (JIA). Cognitive behavioral therapy is often recommended as treatment for chronic fatigue, considering its effectiveness on the group level. However, not everybody benefits on the individual level. More treatment success at the individual level might be achieved with patient-tailored treatments that incorporate the biopsychosocial framework.

Methods: In addition to biological assessments of blood, stool, saliva, and hair, the QFS-study consists of a randomized controlled trial (RCT) in which a single-subject experimental case series (N=1) design will be implemented using Experience Sampling Methodology in fatigued adolescents and young adults with QFS, CFS/ME, and JIA (aged 12-29). With the RCT design, the effectiveness of patient-tailored PROfeel lifestyle advices will be compared against generic dietary advices in reducing fatigue severity at the group level. Pre-post analyses will be conducted to determine relevance of intervention order. By means of the N=1 design, effectiveness of both advices will be measured at the individual level.

Discussion: The QFS-study is a comprehensive study exploring disrupted biological factors and patient-tailored lifestyle advices as intervention in adolescent and young adults with QFS and similar manifestations of chronic fatigue. Practical or operational issues are expected during the study, but can be overcome through innovative study design, statistical approaches, and recruitment strategies. Ultimately, the study aims to contribute to biological research and (personalized) treatment in QFS and similar manifestations of chronic fatigue.

Trial registration: Trial NL8789 . Registered July 21, 2020.

Source: Vroegindeweij A, Swart JF, Houtveen J, Eijkelkamp N, van de Putte EM, Wulffraat NM, Nijhof SL. Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design. Trials. 2022 Aug 19;23(1):683. doi: 10.1186/s13063-022-06620-2. PMID: 35986408.  https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06620-2 (Full text)

 

Long-haul COVID: healthcare utilization and medical expenditures 6 months post-diagnosis

Abstract:

Background: Despite extensive evidence that COVID-19 symptoms may persist for up to a year, their long-term implications for healthcare utilization and costs 6 months post-diagnosis remain relatively unexplored. We examine patient-level association of COVID-19 diagnosis association of COVID-19 diagnosis with average monthly healthcare utilization and medical expenditures for up to 6 months, explore heterogeneity across age groups and determine for how many months post-diagnosis healthcare utilization and costs of COVID-19 patients persist above pre-diagnosis levels.

Methods: This population-based retrospective cohort study followed COVID-19 patients’ healthcare utilization and costs from January 2019 through March 2021 using claims data provided by the COVID-19 Research Database. The patient population includes 250,514 individuals infected with COVID-19 during March-September 2020 and whose last recorded claim was not hospitalization with severe symptoms. We measure the monthly number and costs of total visits and by telemedicine, preventive, urgent care, emergency, immunization, cardiology, inpatient or surgical services and established patient or new patient visits.

Results: The mean (SD) total number of monthly visits and costs pre-diagnosis were .4783 (4.0839) and 128.06 (1182.78) dollars compared with 1.2078 (8.4962) visits and 351.67 (2473.63) dollars post-diagnosis. COVID-19 diagnosis associated with .7269 (95% CI, 0.7088 to 0.7449 visits; P < .001) more total healthcare visits and an additional $223.60 (95% CI, 218.34 to 228.85; P < .001) in monthly costs. Excess monthly utilization and costs for individuals 17 years old and under subside after 5 months to .070 visits and $2.77, persist at substantial levels for all other groups and most pronounced among individuals age 45-64 (.207 visits and $73.43) and 65 years or older (.133 visits and $60.49).

Conclusions: This study found that COVID-19 diagnosis was associated with increased healthcare utilization and costs over a six-month post-diagnosis period. These findings imply a prolonged burden to the US healthcare system from medical encounters of COVID-19 patients and increased spending.

Source: Koumpias AM, Schwartzman D, Fleming O. Long-haul COVID: healthcare utilization and medical expenditures 6 months post-diagnosis. BMC Health Serv Res. 2022 Aug 8;22(1):1010. doi: 10.1186/s12913-022-08387-3. PMID: 35941617; PMCID: PMC9358916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358916/ (Full text)

COVID-19 and Therapeutic Apheresis

Abstract:

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented challenge for the global community. The pathogenesis of COVID-19, its complications and long term sequelae (so called Long/Post-COVID) include, in addition to the direct virus-induced tissues injury, multiple secondary processes, such as autoimmune response, impairment of microcirculation, and hyperinflammation. Similar pathological processes, but in the settings of neurological, cardiovascular, rheumatological, nephrological, and dermatological diseases can be successfully treated by powerful methods of Therapeutic Apheresis (TA).

We describe here the rationale and the initial attempts of TA treatment in severe cases of acute COVID-19. We next review the evidence for the role of autoimmunity, microcirculatory changes and inflammation in pathogenesis of Long/Post COVID and the rationale for targeting those pathogenic processes by different methods of TA. Finally, we discuss the impact of COVID-19 pandemic on patients, who undergo regular TA treatments due to their underlying chronic conditions, with the specific focus on the patients with inherited lipid diseases being treated at the Dresden University Apheresis Center.

Source: Tselmin S, Julius U, Jarzebska N, Rodionov R. COVID-19 and Therapeutic Apheresis. Horm Metab Res. 2022 Aug;54(8):571-577. doi: 10.1055/a-1864-9482. Epub 2022 Aug 9. PMID: 35944525.  https://pubmed.ncbi.nlm.nih.gov/35944525/

Returning to work and the impact of post COVID-19 condition: A systematic review

Abstract:

Background: The COVID-19 pandemic is still ongoing, with rapidly increasing cases all over the world, and the emerging issue of post COVID-19 (or Long COVID-19) condition is impacting the occupational world.

Objective: The aim of this systematic review was to evaluate the impact of lasting COVID-19 symptoms or disability on the working population upon their return to employment.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements we performed a systematic review in December 2021, screening three databases (PubMed, ISI Web of Knowledge, Scopus), for articles investigating return to work in patients that were previously hospitalized due to COVID-19. A hand-searched was then performed through the references of the included systematic review. A quality assessment was performed on the included studies.

Results: Out of the 263 articles found through the initial search, 11 studies were included in this systematic review. The selected studies were divided based on follow-up time, in two months follow-up, follow-up between two and six months, and six months follow-up. All the studies highlighted an important impact of post COVID-19 condition in returning to work after being hospitalized, with differences based on follow-up time, home Country and mean/median age of the sample considered.

Conclusions: This review highlighted post COVID-19 condition as a rising problem in occupational medicine, with consequences on workers’ quality of life and productivity. The role of occupational physicians could be essential in applying limitations to work duties or hours and facilitating the return to employment in workers with a post COVID-19 condition.

Source: Gualano MR, Rossi MF, Borrelli I, Santoro PE, Amantea C, Daniele A, Tumminello A, Moscato U. Returning to work and the impact of post COVID-19 condition: A systematic review. Work. 2022 Aug 1. doi: 10.3233/WOR-220103. Epub ahead of print. PMID: 35938280. https://content.iospress.com/articles/work/wor220103 (Full text)

Mast cell activation syndrome and the link with long COVID

Abstract:

Mast cells are innate immune cells found in connective tissues throughout the body, most prevalent at tissue-environment interfaces. They possess multiple cell-surface receptors which react to various stimuli and, after activation, release many mediators including histamine, heparin, cytokines, prostaglandins, leukotrienes and proteases.

In mast cell activation syndrome, excessive amounts of inflammatory mediators are released in response to triggers such as foods, fragrances, stress, exercise, medications or temperature changes. Diagnostic markers may be difficult to assess because of their rapid degradation; these include urinary N-methyl histamine, urinary prostaglandins D2, DM and F2α and serum tryptase (which is stable) in the UK. Self-management techniques, medications and avoiding triggers may improve quality of life. Treatments include mast cell mediator blockers, mast cell stabilisers and anti-inflammatory agents. ‘Long COVID’ describes post-COVID-19 syndrome when symptoms persist for more than 12 weeks after initial infection with no alternative diagnosis.

Both mast cell activation syndrome and long COVID cause multiple symptoms. It is theorised that COVID-19 infection could lead to exaggeration of existing undiagnosed mast cell activation syndrome, or could activate normal mast cells owing to the persistence of viral particles. Other similarities include the relapse-remission cycle and improvements with similar treatments. Importantly, however, aside from mast cell disorders, long COVID could potentially be attributed to several other conditions.

Source: Arun S, Storan A, Myers B. Mast cell activation syndrome and the link with long COVID. Br J Hosp Med (Lond). 2022 Jul 2;83(7):1-10. doi: 10.12968/hmed.2022.0123. Epub 2022 Jul 26. PMID: 35938771. https://pubmed.ncbi.nlm.nih.gov/35938771/