Category: Overlapping Illnesses

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

Abstract:

Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID.

The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID.

The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review.

It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.

Source: Muzyka, I., Revenko, O., Kovalchuk, I. et al. What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01195-z (Full text)

Long Covid: clues about causes

Abstract:(Full text

Many patients report persistent symptoms after resolution of acute COVID-19, regardless of SARS-CoV-2 variant and even if the initial illness is mild [1, 2]. A multitude of symptoms have been described under the umbrella term ‘Long COVID’, otherwise known as ‘post-COVID syndrome’ or ‘post-acute sequelae of SARS-CoV-2 (PASC)’; for simplicity we will use the term Long COVID.

Symptoms are diverse but include breathlessness, fatigue and brain fog, reported to affect up to 69% of cases [3]. Long COVID can be debilitating, 45.2% of patients requiring a reduced work schedule [4]. The WHO estimates that 17 million people in Europe have experienced Long COVID during the first two years of the pandemic [5]. SARS-CoV-2 variants continue to circulate and the risk of post-acute complications remains; a recent study of 56 003 UK patients found that even after Omicron infection, 4.5% suffered persistent symptoms [6].

It is therefore likely that Long COVID will provide a substantial medical and economic burden for the foreseeable future. There is an urgent need to understand mechanisms of disease and develop effective treatments based on this understanding.

Source: Liew F, Efstathiou C, Openshaw PJ. Long Covid: clues about causes. Eur Respir J. 2023 Mar 23:2300409. doi: 10.1183/13993003.00409-2023. Epub ahead of print. PMID: 36958743; PMCID: PMC10040855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040855/ (Full text)

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis

Abstract:

Background: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors.

Methods: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL.

Results: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS.

Conclusions: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Source: Mastrorosa I, Del Duca G, Pinnetti C, Lorenzini P, Vergori A, Brita AC, Camici M, Mazzotta V, Baldini F, Chinello P, Mencarini P, Giancola ML, Abdeddaim A, Girardi E, Vaia F, Antinori A. What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis. Health Qual Life Outcomes. 2023 Mar 22;21(1):28. doi: 10.1186/s12955-023-02107-z. PMID: 36949439; PMCID: PMC10031164. https://hqlo.biomedcentral.com/articles/10.1186/s12955-023-02107-z (Full text)

Post-COVID Syndrome

Abstract:

Background: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).

Methods: The data presented here were derived from a systematic literature review.

Results: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virus triggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.

Conclusion: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

Source: Hallek M, Adorjan K, Behrends U, Ertl G, Suttorp N, Lehmann C. Post-COVID Syndrome. Dtsch Arztebl Int. 2023 Jan 27;120(4):48-55. doi: 10.3238/arztebl.m2022.0409. PMID: 36633452; PMCID: PMC10060997. https://www.aerzteblatt.de/int/archive/article/229208 (Full text)

What is really ‘Long COVID’?

Abstract:

The previous acute respiratory diseases caused by viruses originating from China or the middle east (e.g., SARS, MERS) remained fast developing short diseases without major sequalae or any long-lasting complications. The new COVID-19, on the other hand, not only that it rapidly spread over the world, but some patients never fully recovered or even if they did, a few weeks later started to complain not only of shortness of breath, if any, but general weakness, muscle pains and ‘brain fog’, i.e., fuzzy memories. Thus, these signs and symptoms were eventually labelled ‘long COVID’, for which the most widely used definition is ‘new signs and symptoms occurring 4-8 weeks after recovering from acute stage of COVID-19’.

The other most frequent manifestations associated with long COVID include headache, loss of memory, smell and of hair, nausea, and vomiting. Thus, long COVID is not a simple disease, but complex disorder of several organ systems malfunctioning; hence, it is probably more appropriate to call this a syndrome.

The pathogenesis of long COVID syndrome is poorly understood, but initial and persistent vascular endothelial injury that often triggers the formation of microthrombi that if dislodged as emboli, damage several organs, especially in the brain, heart and kidney, by creating microinfarcts.

The other major contributory mechanistic factor is the persistent cytokine storm that may last longer in long COVID patients than in others, probably triggered by aggregates of SARS-Co-2 discovered recently in the adrenal cortex, kidney and brain.

The prevalence of long COVID is relatively high, e.g., initially varied 3-30%, and recent data indicate that 2.5% of UK population suffers from this syndrome, while in the US 14.7% of acute COVID-19 patients continued to have symptoms longer than 2 months. Thus, the long COVID syndrome deserves to be further investigated, both from clinical and basic research perspectives.

Source: Szabo S, Zayachkivska O, Hussain A, Muller V. What is really ‘Long COVID’? Inflammopharmacology. 2023 Mar 25:1–7. doi: 10.1007/s10787-023-01194-0. Epub ahead of print. PMID: 36964860; PMCID: PMC10039447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039447/ (Full text)

Risk Factors Associated With Post−COVID-19 Condition A Systematic Review and Meta-analysis

Abstract:

Importance  Post−COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective  To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources  Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study Selection  The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data Extraction and Synthesis  Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main Outcomes and Measures  The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results  The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and Relevance  This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial Registration  PROSPERO Identifier: CRD42022381002

Source: Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 Condition: A Systematic Review and Meta-analysis. JAMA Intern Med. Published online March 23, 2023. doi:10.1001/jamainternmed.2023.0750 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802877 (Full text)

Social support, distress and well-being in individuals experiencing Long-COVID: a cross-sectional survey study

Abstract:

Objectives: Increasingly attention of the COVID-19 pandemic is directed towards its long-term effects, also known as Long-COVID. So far, Long-COVID was examined mainly from a medical perspective, leaving psychosocial effects of Long-COVID understudied. The present study advances the current literature by examining social support in the context of Long-COVID. The study not only examines received support reported by individuals with Long-COVID, but also provided support reported by relatives of individuals with Long-COVID.

Design: Cross-sectional study.

Setting: The study was conducted from June to October 2021 in Austria, Germany and the German-speaking part of Switzerland.

Participants: We examined 256 individuals with Long-COVID (MAge=45.05 years, 90.2% women) and 50 relatives of individuals with Long-COVID (MAge=48.34 years, 66.1% female) in two separate online surveys, assessing social support, well-being and distress.

Primary outcome measures: Primary outcomes were positive and negative affect, anxiety and depressive symptoms and perceived stress.

Results: For individuals with Long-COVID, receiving emotional support was related to higher well-being (positive affect: b=0.29, p<0.01; negative affect: b=-0.31, p<0.05) and less distress (anxiety: b=-1.45, p<0.01; depressive symptoms: b=-1.04, p<0.05; perceived stress: b=-0.21, p<0.05) but no effects emerged for receiving practical support. For relatives of individuals with Long-COVID, providing emotional support was only related to lower depressive symptoms (b=-2.57, p<0.05). Again, provided practical support was unrelated to the outcomes considered.

Conclusions: Emotional support is likely to play an important role in well-being and distress of patients and relatives, whereas practical support does not seem to make a difference. Future research should clarify under what conditions different kinds of support unfold their positive effects on well-being and distress in the context of Long-COVID.

Source: Lüscher J, Scholz U, Bierbauer W. Social support, distress and well-being in individuals experiencing Long-COVID: a cross-sectional survey study. BMJ Open. 2023 Mar 22;13(3):e067166. doi: 10.1136/bmjopen-2022-067166. PMID: 36948566; PMCID: PMC10039976. https://bmjopen.bmj.com/content/13/3/e067166 (Full text)

LC, POTS, and ME/CFS: Lifting the Fog

Abstract:

These three syndromes – long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – have many symptoms in common. The common denominator remains elusive.
The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis.
In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT).
The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.
Source: Chambers, P. LC, POTS, and ME/CFS: Lifting the Fog. Preprints.org 2023, 2023030418. https://doi.org/10.20944/preprints202303.0418.v1 (Full text available as PDF file)

Online Health Communities in Controversy over ME/CFS and Long Covid

Abstract:

The condition known variously as myalgic encephalomyelitis, chronic fatigue syndrome, or ME/CFS has been steeped in controversy for 40 years or more. Long Covid, first noticed and named in 2020, has become entangled with the ME/CFS controversy because of striking similarities in the experiences of patients suffering from the two illnesses. Online health communities (OHCs) have played central roles in both controversies, but these are not the kinds of roles that have been so well-documented in prior literature.

While prior research has established many ways in which participation in an OHC may benefit or otherwise affect community members themselves, this essay focuses on how OHCs contribute to positional shifts in health controversies that involve other communities as well. Using a framework for understanding health controversies as argumentative polylogues, I show that OHCs arguing with other players have made contributions that are both effective in gaining ground for the OHCs’ own goals and in elevating the overall quality of the debate. Further, in some cases these contributions have been so innovative as to suggest surprising future trajectories for OHCs.

Source: Jackson, S. (2023). Online Health Communities in Controversy over ME/CFS and Long Covid. European Journal of Health Communication, 4(2), 49–72. https://doi.org/10.47368/ejhc.2023.203 https://ejhc.org/article/view/3559/2989 (Full text)

Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study

Abstract:

Background: We aimed to characterise the long-term health outcomes of survivors of severe acute respiratory syndrome (SARS) and determine their recovery status and possible immunological basis.

Methods: We performed a clinical observational study on 14 health workers who survived SARS coronavirus infection between Apr 20, 2003 and Jun 6, 2003 in Haihe Hospital (Tianjin, China). Eighteen years after discharge, SARS survivors were interviewed using questionnaires on symptoms and quality of life, and received physical examination, laboratory tests, pulmonary function tests, arterial blood gas analysis, and chest imaging. Plasma samples were collected for metabolomic, proteomic, and single-cell transcriptomic analyses. The health outcomes were compared 18 and 12 years after discharge. Control individuals were also health workers from the same hospital but did not infect with SARS coronavirus.

Findings: Fatigue was the most common symptom in SARS survivors 18 years after discharge, with osteoporosis and necrosis of the femoral head being the main sequelae. The respiratory function and hip function scores of the SARS survivors were significantly lower than those of the controls. Physical and social functioning at 18 years was improved compared to that after 12 years but still worse than the controls. Emotional and mental health were fully recovered. Lung lesions on CT scans remained consistent at 18 years, especially in the right upper lobe and left lower lobe lesions. Plasma multiomics analysis indicated an abnormal metabolism of amino acids and lipids, promoted host defense immune responses to bacteria and external stimuli, B-cell activation, and enhanced cytotoxicity of CD8+ T cells but impaired antigen presentation capacity of CD4+ T cells.

Interpretation: Although health outcomes continued to improve, our study suggested that SARS survivors still suffered from physical fatigue, osteoporosis, and necrosis of the femoral head 18 years after discharge, possibly related to plasma metabolic disorders and immunological alterations.

Funding: This study was funded by the Tianjin Haihe Hospital Science and Technology Fund (HHYY-202012) and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-063B, TJYXZDXK-067C).

Source: Li K, Wu Q, Li H, Sun H, Xing Z, Li L, Chen H. Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study. EClinicalMedicine. 2023 Apr;58:101884. doi: 10.1016/j.eclinm.2023.101884. Epub 2023 Feb 27. PMID: 36873427; PMCID: PMC9969173.