Tag: BMI

Role of the complement system in Long COVID

Abstract:

Long COVID, or Post-Acute COVID Syndrome (PACS), may develop following SARS-CoV-2 infection, posing a substantial burden to society. Recently, PACS has been linked to a persistent activation of the complement system (CS), offering hope for both a diagnostic tool and targeted therapy. However, our findings indicate that, after adjusting proteomics data for age, body mass index and sex imbalances, the evidence of complement system activation disappears.

Furthermore, proteomic analysis of two orthogonal cohorts—one addressing PACS following severe acute phase and another after a mild acute phase—fails to support the notion of persistent CS activation. Instead, we identify a proteomic signature indicative of either ongoing infections or sustained immune activation similar to that observed in acute COVID-19, particularly within the mild-PACS cohort.

Source: Vadim Farztdinov, Boris Zühlke, Franziska Sotzny, Fridolin Steinbeis, Martina Seifert, Claudia Kedor, Kirsten Wittke, Pinkus Tober-Lau, Thomas Zoller, Kathrin Textoris-Taube, Daniela Ludwig, Clemens Dierks, Dominik Bierbaum, Leif Erik Sander, Leif G Hanitsch, Martin Witzenrath, Florian Kurth, Michael Mülleder, Carmen Scheibenbogen, Markus Ralser. Role of the complement system in Long COVID. medRxiv 2024.03.14.24304224; doi: https://doi.org/10.1101/2024.03.14.24304224 https://www.medrxiv.org/content/10.1101/2024.03.14.24304224v1.full-text (Full text)

Association of vaccine status, reinfections, and risk factors with Long COVID syndrome

Abstract:

The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients’ comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment.

Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05).

Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor.

We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

Source: Romero-Ibarguengoitia ME, Rodríguez-Torres JF, Garza-Silva A, Rivera-Cavazos A, Morales-Rodriguez DP, Hurtado-Cabrera M, Kalife-Assad R, Villarreal-Parra D, Loose-Esparza A, Gutiérrez-Arias JJ, Mata-Porras YG, Ojeda-Salazar DA, Sanz-Sánchez MA, González-Cantú A, Azzolini E, Rescigno M. Association of vaccine status, reinfections, and risk factors with Long COVID syndrome. Sci Rep. 2024 Feb 2;14(1):2817. doi: 10.1038/s41598-024-52925-4. PMID: 38307886; PMCID: PMC10837423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837423/ (Full text)

The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study

Abstract:

Long Covid-19 syndrome (LCS) manifests with a wide range of clinical symptoms, yet the factors associated with LCS remain poorly understood. The current study aimed to investigate the relationships that demographic characteristics, clinical history, laboratory indicators, and the frequency of HLA-I alleles have with the likelihood of developing LCS.

We extracted the demographic characteristics and clinical histories from the medical records of 88 LCS cases (LCS+ group) and 96 individuals without LCS (LCS− group). Furthermore, we evaluated the clinical symptoms, serum levels of interleukin (IL)-6 and tumor necrosis factor-α, laboratory parameters, and the frequencies of HLA-I alleles.

Following this we used multiple logistic regression to investigate the association these variables had with LCS. Subjects in the LCS+ group were more likely to have experienced severe Covid-19 symptoms and had higher body mass index (BMI), white blood cell, lymphocyte counts, C-reactive protein (CRP), and IL-6 levels than those in the LCS− group (for all: P < 0.05).

Moreover, the frequencies of the HLA-A*11, -B*14, -B*38, -B*50, and -C*07 alleles were higher in the LCS+ group (for all: P < 0.05). After adjusting for the most important variables, the likelihood of suffering from LCS was significantly associated with BMI, CRP, IL-6, the HLA-A*11, and -C*07 alleles, as well as a positive history of severe Covid-19 (for all: P < 0.05).

Our study showed that a history of severe Covid-19 during the acute phase of the disease, the HLA-A*11, and -C*07 alleles, higher BMI, as well as elevated serum CRP and IL-6 levels, were all associated with an increased likelihood of LCS.

Source: Torki, E., Hoseininasab, F., Moradi, M. et al. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med 24, 1 (2024). https://doi.org/10.1007/s10238-023-01256-1 https://link.springer.com/article/10.1007/s10238-023-01256-1 (Full text)

A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls

Abstract:

Background: Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are debilitating disorders that significantly affect the daily lives of those suffering from them, as well as their loved ones. Both conditions have overlapping clinical features that resemble inflammatory disorders, and overlapping symptoms, such as depression, suggest central nervous system (CNS) involvement. The role of the immune system’s soluble messengers in the pathogenesis of CFS and FM has been under investigation, but so far the results are inconclusive. In addition, there is growing evidence that the kynurenine pathway is involved in the pathology of diseases related to the CNS, yet the role of each metabolite is not clear. The relationship between kynurenine metabolism and CFS and FM has not been extensively explored. Few studies have simultaneously examined the immunological status in both CFS and FM, making this thesis the first to comprehensively evaluate the potential distinct immunological differences between the two disorders.

Objective: The objective of this study was to compare the CFS and FM with healthy controls, regarding the levels of several soluble blood markers related to the immune system. The markers chosen were:

  • The inflammatory marker high-sensitive CRP (hsCRP)
  • The following cytokines and chemokines: Interferon (IFN)-γ, Interleukin (IL)-1β, IL1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α
  • The metabolites and their ratios of the kynurenine pathway: Tryptophan (Try), kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid (AA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA) and picolinic acid (Pic).

Method: The population consisted of three groups: CFS patients (n = 49), FM patients (n = 58), and healthy controls (n = 54). All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university.

Plasma levels of hsCRP were analysed at the hospital. The cytokines and chemokines IFN-γ, IL-1β, IL-1ra, xii IL-4, IL-6, IL-8, IL-10, IL-17, IP-10, MCP-1, TGF-β1, TGF-β2, TGF-β3, and TNF-α were analysed by multiplex. Kynurenine metabolites were analysed by LC-MS/MS.

Linear regression models of log-transformed data for hsCRP and the kynurenine metabolites were conducted for comparison of the three groups CFS, FM and controls. The Kruskal-Wallis test was used to analyse differences of cytokines between the three groups. Main findings were controlled for age, body mass index (BMI), and symptoms of anxiety and depression.

Results: hsCRP levels were significantly higher for both the CFS and FM groups compared to healthy controls when adjusting for age and BMI (p = .006). There was no difference between the two patient groups. Level of hsCRP was affected by BMI (p < .001) but not age.

MCP-1 was significantly increased in both patient groups compared to healthy controls (p < .001). IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3 (all p < .001), IL-10 (p = .003) and IL17 (p = .002) all were significantly lower in the patient groups compared to healthy controls. IFN-γ was significantly lower in the FM group (p < .001). For IL-8, IP-10 and IL1ra there were no significant difference.

QA differed between CFS and FM patients (p = .036) and was related to higher levels of BMI (p = .002). The KA/QA ratio was lower for CFS patients compared to healthy controls (p = .016). The KA/HK ratio was lower for FM patients compared to healthy controls, and this lower ratio was associated with increased symptoms of pain (p = .002). The kynurenine aminotransferase II (KAT II) enzymatic activity given by XA/HK was lower for FM patients compared to healthy controls (p = .013). In addition, BMI was negatively associated with enhanced KAT II enzymatic activity (p = .039).

Symptoms of anxiety and depression were not associated with any of the immune markers studied.

Conclusion: In our material hsCRP and MCP-1 are increased in patients both with CFS and with FM, while several other cytokines are either similar or significantly lower in patients than controls. Our study also indicates associations between kynurenine metabolism and CFS and FM. Kynurenine also is associated with single symptoms such as fatigue and pain. Forthcoming studies indicating interactions and causative effects, or restoration of the inflammatory status, may place cytokines and kynurenine metabolites as a target for treatment as well as prevention of these conditions in the future.

Source: Groven, Nina. A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls. PhD Thesis [Norwegian University of Science and Technology] https://ntnuopen.ntnu.no/ntnu-xmlui/handle/11250/3072207 (Full text available as PDF file)

Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19 infection

Abstract:

Objective and design: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is a major symptom of the long-COVID syndrome. The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19 infection.

Subjects and methods: We tested this hypothesis by analysing pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19 positive and COVID-19 negative participants were categorized based on antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale.

Results: COVID-19 positive participants exhibited mild symptoms of infection. Chronic fatigue was a prevalent symptom among this population and was significantly higher in the COVID-19 positive participants than COVID-19 negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in COVID-19 positive and COVID-19 negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in COVID-19 negative, but not COVID-19 positive
individuals. Raised BMI was associated with chronic fatigue in COVID-19 positive participants.

Conclusions: We found evidence that pre-existing increased levels of IL-6 provide the ground for chronic fatigue symptoms but there was no specific link seen with mild COVID-19 status. Elevated BMI increased the risk of chronic fatigue in mild COVID-19 infection consistent with previous reports.

Source: B Freidin, M., Borsini, A., Pariante, C., & MK Williams, F. (2023). Long-COVID fatigue is not predicted by prepandemic plasma IL-6 levels in mild COVID-19 infection. Inflammation Research. https://kclpure.kcl.ac.uk/portal/files/201594849/Freidin_et_al._2023.pdf (Full text)

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study

Abstract:

Objective: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID.

Design: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages.

Setting: Israeli general practice.

Subjects: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and ,936 without a history of SARS-CoV-2 infection.

Main outcome measures: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms.

Results: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness.

Conclusion: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.

Key Points

Long-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

Source: Adler L, Gazit S, Pinto Y, Perez G, Mizrahi Reuveni M, Yehoshua I, Hoffman R, Azuri J, Patalon T. Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study. Scand J Prim Health Care. 2022 Oct 31:1-8. doi: 10.1080/02813432.2022.2139480. Epub ahead of print. PMID: 36314555. https://www.tandfonline.com/doi/full/10.1080/02813432.2022.2139480 (Full text)

Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients

Abstract:

Background and objectives: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

Methods: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants’ demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients’ characteristic and COVID-19 course was evaluated.

Result: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD=11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

Conclusion: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.

Source: Azadvari M, Haghparast A, Nakhostin-Ansari A, Emami Razavi SZ, Hosseini M. Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients. Heliyon. 2022 Aug 11:e10148. doi: 10.1016/j.heliyon.2022.e10148. Epub ahead of print. PMID: 35971463; PMCID: PMC9367176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367176/ (Full text)

Factors affecting duration of chronic fatigue syndrome in pediatric patients

Abstract:

OBJECTIVE: To determine factors affecting duration of chronic fatigue syndrome (CFS) in pediatric patients.

METHODS: This Retrospective cohort consisted of patients with CFS at the regional referral infectious disease clinic for evaluation of fatigue in children and adolescents. Demographic, clinical, and laboratory data were analyzed to identify the impact on duration and severity of pediatric CFS.

RESULTS: A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria. No association was found between the CFS symptoms, gender, or age at diagnosis and duration of fatigue symptoms. Duration of CFS was associated with high Body-Mass Index (BMI) in a regression model after adjustment for patient’s age, gender, and seropositive status for B. burgdorferi and/or EBV (0.34 ± 0.15, P < 0.04).

CONCLUSIONS: BMI is significantly associated with prolonged duration of CFS.

 

Source: Petrov D, Marchalik D, Sosin M, Bal A. Factors affecting duration of chronic fatigue syndrome in pediatric patients. Indian J Pediatr. 2012 Jan;79(1):52-5. doi: 10.1007/s12098-011-0463-4. Epub 2011 May 27. https://www.ncbi.nlm.nih.gov/pubmed/21617905