COVID-19 in inherited metabolic disorders: Clinical features and risk factors for disease severity.

BACKGROUND: Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center. METHODS: Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD. RESULTS: Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults. DISCUSSION: This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.

New Horizons: the value of UK Biobank to research on endocrine and metabolic disorders.

UK Biobank is an intensively characterized prospective study of 500 000 men and women, aged 40 to 69 years when recruited, between 2006 and 2010, from the general population of the United Kingdom. Established as an open-access resource for researchers worldwide to perform health research that is in the public interest, UK Biobank has collected (and continues to collect) a vast amount of data on genetic, physiological, lifestyle, and environmental factors, with prolonged follow-up of heath conditions through linkage to administrative electronic health records. The study has already demonstrated its unique value in enabling research into the determinants of common endocrine and metabolic diseases. The importance of UK Biobank, heralded as a flagship project for UK health research, will only increase over time as the number of incident disease events accrue, and the study is enhanced with additional data from blood assays (such as whole-genome sequencing, metabolomics, and proteomics), wearable technologies (including physical activity and cardiac monitors), and body imaging (magnetic resonance imaging and dual-energy X-ray absorptiometry). This unique research resource is likely to transform our understanding of the causes, diagnosis, and treatment of many endocrine and metabolic disorders.

Eating Disorders and Metabolic Diseases.

Eating disorders are complex diseases with multifactorial causes. According to the Diagnostic and Statistical Manual of Mental Disorders text version (DSM-5-TR) and the WHO International Classification of Diseases and Related Health Problems (ICD-11), the major types of eating disorders include anorexia nervosa, bulimia nervosa, and binge eating disorder. The prevalence of eating disorders is alarmingly increasing globally. Moreover, the COVID-19 pandemic has led to more development and worsening of eating disorders. Patients with eating disorders exhibit high rates of psychiatric comorbidities and medical comorbidities such as obesity, diabetes, and metabolic syndrome. This paper aims to review and discuss the comorbidities of eating disorders with those metabolic diseases. Eating disorder treatment typically includes a combination of some or all approaches such as psychotherapy, nutrition education, and medications. Early detection and intervention are important for the treatment of eating disorders.

COVID-19 in Unvaccinated patients with inherited metabolic disorders: A single center experience.

Patients with certain inherited metabolic disorders (IMD) are at high risk for metabolic decompensation with exposure to infections. The COVID-19 pandemic has been particularly challenging for health care providers dealing with IMD patients, in view of its unpredictable consequences in these patients. There is limited data in literature on evaluating the impact and the outcome of COVID-19 infection in these patients. This cross-sectional retrospective study on a large cohort of unvaccinated IMD patients, reviewed the incidence of COVID-19 infection, disease manifestation and outcome during the pandemic between November 2019 and July 2021. In this cohort of 1058 patients, 11.7% (n = 124) were infected with COVID-19. Their median age was 16 years (age range 2-42); 57% (n = 71) were males. Post-exposure positive test was noted in 78% (n = 97) patients, while 19% (n = 24) had symptomatic diagnosis and three patients tested positive during pre-hospital visits screening. Most patients, 68.5% (n = 85) had mild COVID-19 related symptoms such as fever, cough, headache and diarrhea while 13.7% (n = 17) patients had no symptoms. Of twenty-two patients (17.7%) who required hospitalization, 16 were adults with various intoxication and energy metabolism disorders, who developed IMD related complications such as metabolic acidosis, hyperammonemia, acute pancreatitis, hypoglycemia, rhabdomyolysis and thrombosis. Ten patients needed intensive care management. The cohort death rate was 2.4% (3 patients). Overall, the clinical course of COVID-19 infection in these IMD patients was relatively mild except for patients with intoxication and energy metabolism disorders who had high risk of developing acute metabolic decompensation with severe complications.

Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study.

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.

One year of COVID-19: infection rates and symptoms in patients with inherited metabolic diseases followed by MetabERN.

BACKGROUND: Since the beginning of the COVID-19 pandemic, MetabERN has been monitoring the SARS-CoV-2 infection rates within its metabolic community. To gather data on the total number of cases and the severity of symptoms among IMD patients one year into the pandemic, an online survey was distributed among all MetabERN healthcare providers (HCP). Epidemiological analysis was performed by integrating the survey's data with the MetabERN database. RESULTS: Survey's respondents reported a total of 452 cases of COVID-19 among their IMD patients (213 paediatric and 239 adults). Considering the total number of patients followed by the respondents (n = 26,347), the registered prevalence of COVID-19 in the IMD population was of 1716 × 100,000. Italy emerged as the most affected country (25.4% of cases), followed by the United Kingdom (14.2% of cases). Most of the paediatric cases of COVID-19 displayed no or mild symptoms during the disease: 34% of HCP reported having asymptomatic patients in 75-100% of cases, while 37.5% reported mild symptoms in about a quarter of their patients. Similarly to paediatric cases, most adult IMD patients with COVID-19 were asymptomatic or had mild symptoms: about one third of respondents reported 75-100% asymptomatic patients and about 65% of HCP had between 0 and 50% of patients with mild symptoms. The majority of the respondents reported no deaths due to COVID-19 in adult and paediatric patients with IMDs. CONCLUSIONS: Most of MetabERN's IMD patients who got COVID-19 during the first year of the pandemic had mild symptoms and a positive outcome of the disease. However, fatal events were recorded in paediatric patients; this, together with the lack of information on the long-term effects of COVID-19 in IMDs, call for caution in the metabolic population.

Real world data on cardiometabolic diseases in U.S. adults during the SARS-CoV-2 pandemic: a decentralized registry study.

BACKGROUND: Pre-existing cardiometabolic comorbidities place SARS-CoV-2 positive patients at a greater risk for poorer clinical course and mortality than those without it. We aimed to analyze real-world registry data focused primarily on participants with cardiometabolic diseases (CMD), which were remotely obtained via a digital platform. METHODS: Participants were divided into two groups: CMD or no cardiometabolic disease (non-CMD). They were evaluated based on their medical history, current medications/supplements, COVID-19 status, demographics, and baseline characteristics. The frequency of medications/supplements for CMD were compared using relative risks and 95% confidence intervals. The WHO (Five) Well-Being Index (WHO-5) were collected monthly for 6 months to assess psychological well-being which included cheerfulness, calmness, vigor, rest, and engagement with daily activities of interest. RESULTS: The 791 enrollees represented 49 U.S. states. The CMD group had significantly higher (p < 0.0001) BMI (mean + 3.04 kg/m2) and age (mean + 9.15 years) compared to non-CMD group. In the CMD group, participants who tested positive for COVID-19 had lower (p < 0.0001) well-being scores than those without COVID-19. For the 274 participants on CMD medications/supplements, there was no statistical difference in risk of COVID-19 contracture based on medication/supplement type; however, all six participants who were not being treated for CMD were COVID-19 positive (RR ~ 104). For 89 participants who were on treatment for diabetes or insulin resistance, there was a 90% reduced risk of COVID-19 incidence (p = 0.0187). CONCLUSION: The well-being score of the CMD group was dependent on whether they tested positive for COVID-19. Type of CMD treatment did not impact COVID-19 status, but absence of treatment significantly increased COVID-19 incidence. With respect to SARS-CoV-2, our analysis supports continued use of the statins, ACE-I, ARBs, and diabetes medications in CMD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04348942.

COVID-19 and metabolic disease: mechanisms and clinical management.

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

Multifactorial Basis and Therapeutic Strategies in Metabolism-Related Diseases.

Throughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases. Therefore, understanding the underlying molecular mechanisms of these diseases leads us to develop more accurate and effective treatments to reduce or mitigate their prevalence in the population. Given the global relevance of NCDs and ongoing research progress, this article reviews the current understanding about NCDs and their related risk factors, with a focus on obesity, diabetes, MAFLD, and CVDs, summarizing the knowledge about their pathophysiology and highlighting the currently available and emerging therapeutic strategies, especially pharmacological interventions. All of these diseases play an important role in the contamination by the SARS-CoV-2 virus, as well as in the progression and severity of the symptoms of the coronavirus disease 2019 (COVID-19). Therefore, we briefly explore the relationship between NCDs and COVID-19.

[Impact of cardiovascular metabolic diseases on COVID-19: review of recent progress].

The high comorbidity between cardiovascular and metabolic diseases (CVMD) and coronavirus disease 2019 (COVID-19) and the consequent high mortality and the potential risk of cardiovascular damage have brought great challenges to the clinical diagnosis and treatment of the condition. The latest studies found that advanced age, immune function defects, inflammatory factor storms and oxidative stress damage all potentially contribute to the high comorbidity of the two. Direct virus invasion, myocardial oxygen supply and demand imbalance and vascular endothelial and coagulation dysfunction may be important mechanisms for cardiovascular injury in COVID-19 patients. In addition, the expression level of ACE2 (the cell membrane receptor of SARS-CoV-2) in various organs and the peripheral blood not only mediates the direct invasion and damage of the organs, but also participates in regulation of the balance of systematic inflammation and oxidative stress, thus affecting the susceptibility and outcomes of the patients. Herein we review the recent research progress in the comorbidity between COVID-19 and CVMD and explore the mechanisms of cardiovascular damage caused by SARS-CoV-2, thus to provide a theoretical basis for the clinical diagnosis and treatment of COVID-19 with underlying CVMD.

Avoiding the Coming Tsunami of Common, Chronic Disease: What the Lessons of the COVID-19 Pandemic Can Teach Us.

During the past year, clinicians and the public have been focused on the coronavirus disease 2019 (COVID-19) pandemic and its associated societal and economic effects. However, once the acute phase of this crisis has passed, we will face an enormous wave of death and disability as a result of common chronic diseases (CCDs), with cardiometabolic diseases at the crest (Figure). A tsunami results when an earthquake on the ocean floor creates huge waves that can wreak devastation far distant from the original upheaval, especially when warnings are ignored. Similarly, underlying global and national demographic and risk factor profiles have for some time presaged an overwhelming burden of CCDs. However, although the pandemic has created additional impetus that unless heeded will amplify the consequences of this burden, the rapid adaptations and innovations in care and research prompted by the urgent response to it may also offer us the means to stem this flood.

COVID-19 and metabolic diseases: a heightened awareness of health inequities and a renewed focus for research priorities.

Chronic metabolic disorders such as diabetes and obesity are major public health issues in the United States. However, significant disparities in their prevalence and incidence place a greater burden on US racial and ethnic minority groups, contributing to worse COVID-19 outcomes in many. Improving treatment and prevention of diabetes and obesity is critical to the NIDDK. In this Perspective, we will review the burden of metabolic diseases in the United States, the observed disparities for metabolic diseases in relation to COVID-19, and research opportunities to address underlying causes of metabolic diseases, their associated health disparities, and COVID-19.

Cardiometabolic vigilance in COVID-19 and resource husbandry in resource-challenged times: Clinical practice- based expert opinion.

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.

COVID-19 changes the lifestyle of the population and subtly reduces the incidence of metabolic disease.

The COVID-19 pandemic has placed significant restrictions on people's daily activities and even change their eating habits, yet it has inadvertently allowed people to benefit potentially from this restriction for certain diseases. The COVID-19 outbreak has had the positive effect of changing the nutritional status of some populations. From this point of view, the COVID-19 pandemic is cleverly beneficial.