Tag: obesity

Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6–12 Months Postinfection

Abstract:

Background: Few longitudinal studies available characterize long COVID outcomes out to 24 months, especially in people with nonsevere acute coronavirus disease 2019 (COVID-19). This study sought to prospectively characterize incidence and duration of long COVID symptoms and their association with quality of life (QoL) from 1–24 months after mild-to-moderate COVID-19 using validated tools in a diverse cohort of unvaccinated people infected with SARS-CoV-2 in 2020.

Methods: At 1–3, 6, 12, 18, and 24 months post-COVID-19, 70 participants had orthostatic vital signs measured, provided blood, and completed surveys characterizing symptoms, QoL, and return to pre-COVID-19 health and activities using validated tools (FLU-PRO+, Fatigue Severity Scale, Insomnia Severity Index, General Practitioner Assessment of Cognition, Patient Health Questionnaire Depression 8-Item, Generalized Anxiety Disorder 7-Item, 36-Item Short-Form Health Survey, EuroQol EQ-5D-5L).

Results: During the study period, 33% of participants experienced long COVID (had not returned to pre-COVID-19 health status and reported at least 1 symptom >90 days postinfection); 8% had not returned to their pre-COVID-19 health status 24 months postinfection. Long COVID symptoms peaked 6 months post-COVID-19, frequently causing activity limitations. Having long COVID was significantly associated with decreased QoL in multiple domains. Frequencies of orthostatic hypotension and tachycardia reflected levels reported in the general population. Within-person weight increased significantly between months 1 and 6. Long COVID was associated with pre-COVID-19 obesity and hyperlipidemia, but not with high-sensitivity C-reactive protein levels 1–3 months postinfection.

Conclusions: Long COVID occurs in a significant proportion of unvaccinated people, even if the acute illness was not severe. Long COVID prevalence peaked 6–12 months post-COVID-19, and a small proportion of participants still reported not returning to their pre-COVID-19 health status 24 months post-COVID-19.

Source: Demko ZO, Yu T, Mullapudi SK, Varela Heslin MG, Dorsey CA, Payton CB, Tornheim JA, Blair PW, Mehta SH, Thomas DL, Manabe YC, Antar AAR. Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6-12 Months Postinfection. Open Forum Infect Dis. 2024 Mar 6;11(3):ofae027. doi: 10.1093/ofid/ofae027. PMID: 38449921; PMCID: PMC10917418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917418/ (Full text)

High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study

Abstract:

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections.

The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection.

In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC.

In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Source: Villa A, Milito C, Deiana CM, Gambier RF, Punziano A, Buso H, Bez P, Lagnese G, Garzi G, Costanzo G, Giannuzzi G, Pagnozzi C, Dalm VASH, Spadaro G, Rattazzi M, Cinetto F, Firinu D. High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study. J Clin Immunol. 2024 Feb 6;44(2):59. doi: 10.1007/s10875-024-01656-2. PMID: 38319477; PMCID: PMC10847195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847195/ (Full text)

COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children

Abstract:

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the ‘Respiratory Diseases of Pediatric Interest Unit’ at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania ‘Luigi Vanvitelli’, were selected during the timeframe from September 2021 to October 2022.
The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS).
In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.
Source: Indolfi C, Klain A, Dinardo G, D’Addio E, Ferrara S, Decimo F, Ciprandi G, Tosca MA, Miraglia del Giudice M. COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children. Children. 2024; 11(2):166. https://doi.org/10.3390/children11020166 https://www.mdpi.com/2227-9067/11/2/166 (Full text)

Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe

Abstract:

Background: Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study.

Methods: A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe’s (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID.

Results: Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents’ place of residence.

Conclusion: Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

Source: Wilk P, Stranges S, Cuschieri S. Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe. Int J Obes (Lond). 2024 Jan 29. doi: 10.1038/s41366-024-01477-8. Epub ahead of print. PMID: 38287094. https://pubmed.ncbi.nlm.nih.gov/38287094/

Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance

Abstract:

Background Post-acute sequelae of COVID-19 (PASC) affects a significant portion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom.

Study Objective This study aimed to characterize the invasive hemodynamic abnormalities of PASC-related exertional intolerance using a larger data set from invasive cardiopulmonary exercise testing (iCPET).

Study Design & Intervention Fifty-five patients were recruited from the Yale Post-COVID-19-Recovery-Program, with most experiencing mild acute illness. Supine right heart catheterization (RHC) and iCPET were performed on all participants.

Main results The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group), On average, the PASC alone group exhibited a “normal” peak exercise capacity, VO2 (89±18% predicted). Approximately 25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise HFpEF and 2 with exercise PH). PASC patient with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak VO2 and cardiac output >80% respectively) despite aberrant central cardiopulmonary exercise hemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group compromising of obese non-PASC group (n=61) derived from historical iCPET cohort was used. The non-PASC obese patients with preserved peak VO2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10%predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of current study also highlights the prevalence of a distinct high output failure HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Source: Peter A. Kahn, Phillip Joseph, Paul M. Heerdt, Inderjit Singh. Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance. ERJ Open Research Jan 2023, 00714-2023; DOI: 10.1183/23120541.00714-2023 https://openres.ersjournals.com/content/early/2023/12/07/23120541.00714-2023 (Full text available as PDF file)

Predictive models of long COVID

Abstract:

Background: The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future.

Methods: We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models – logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the ‘long COVID’ label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n = 2,190,579; diagnosed with long COVID = 17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741).

Findings: LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75.

Interpretation: ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology.

Source: Antony B, Blau H, Casiraghi E, Loomba JJ, Callahan TJ, Laraway BJ, Wilkins KJ, Antonescu CC, Valentini G, Williams AE, Robinson PN, Reese JT, Murali TM; N3C consortium. Predictive models of long COVID. EBioMedicine. 2023 Oct;96:104777. doi: 10.1016/j.ebiom.2023.104777. Epub 2023 Sep 4. PMID: 37672869; PMCID: PMC10494314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494314/ (Full text)

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)

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)

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study

Abstract:

Background: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study.

Methods: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up.

Results: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1β (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome.

Conclusion: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Source: Torres-Ruiz J, Lomelín-Gascón J, Lira Luna J, Vargas-Castro AS, Pérez-Fragoso A, Nuñez-Aguirre M, Alcalá-Carmona B, Absalón-Aguilar A, Balderas-Miranda JT, Maravillas-Montero JL, Mejía-Domínguez NR, Núñez-Álvarez C, Llorente L, Romero-Ramírez S, Sosa-Hernández VA, Cervantes-Díaz R, Juárez-Vega G, Meza-Sánchez D, Rull-Gabayet M, Martínez-Juárez LA, Morales L, López-López LN, Negrete-Trujillo JA, Falcón-Lezama JA, Valdez-Vázquez RR, Gallardo-Rincón H, Tapia-Conyer R, Gómez-Martín D. Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study. Infect Dis (Lond). 2023 Jan 13:1-12. doi: 10.1080/23744235.2022.2158217. Epub ahead of print. PMID: 36637466. https://www.tandfonline.com/doi/full/10.1080/23744235.2022.2158217 (Full text)

Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study

Abstract:

Introduction Tissue damage, chronic dysfunction, and symptoms that last more than 12 weeks are hallmarks of long-term chronic opportunistic viral infection (COVID-19), and the disease may have a permanent, relapsing/remitting, or gradually improving course. This study aimed to determine the risk factors of severe long COVID-19.

Methods In October 2021, primary care clinics enrolled consenting 18- to 89-year-olds to complete an online questionnaire on self-diagnosis, clinician diagnosis, testing, symptom presence, and duration of COVID-19. Long COVID-19 was identified if symptoms were beyond 12 weeks. Patients with long-lasting COVID-19 symptoms were assessed using multivariable regression to identify potential predictors of severe long COVID-19.

Results Of the 220 respondents, 108 (49%) patients were self- or clinician-diagnosed with COVID-19 or had a confirmed positive laboratory test result. Patients aged >45 years and with at least 15 COVID-19 symptoms were 5.55 and 6.02 times, respectively, more likely to acquire severe long COVID-19. Most patients with severe and moderate post-acute COVID-19 syndrome had no relevant comorbidities (p=0.0402; odds ratio [OR]=0.4; 95% confidence interval [CI]=0.18-0.98). Obesity was a significant predictor (p=0.0307; OR=6.2; 95% CI=1.1-33.2).

Conclusion The simultaneous presence of 15 or more COVID-19 symptoms, age >45 years, and obesity were related to a higher probability of severe long COVID-19.

Source: Menezes AS Jr, Botelho SM, Santos LR, Rezende AL. Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study. Cureus. 2022 Oct 2;14(10):e29826. doi: 10.7759/cureus.29826. PMID: 36204261; PMCID: PMC9527039.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527039/ (Full text)