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Open accessJournal ArticleDOI: 10.1016/J.CMET.2021.01.016

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning.

02 Mar 2021-Cell Metabolism (Elsevier)-Vol. 33, Iss: 3, pp 479-498
Abstract: The increased prevalence of obesity, diabetes, and cardiovascular risk factors in people hospitalized with severe COVID-19 illness has engendered considerable interest in the metabolic aspects of SARS-CoV-2-induced pathophysiology. Here, I update concepts informing how metabolic disorders and their co-morbidities modify the susceptibility to, natural history, and potential treatment of SARS-CoV-2 infection, with a focus on human biology. New data informing genetic predisposition, epidemiology, immune responses, disease severity, and therapy of COVID-19 in people with obesity and diabetes are highlighted. The emerging relationships of metabolic disorders to viral-induced immune responses and viral persistence, and the putative importance of adipose and islet ACE2 expression, glycemic control, cholesterol metabolism, and glucose- and lipid-lowering drugs is reviewed, with attention to controversies and unresolved questions. Rapid progress in these areas informs our growing understanding of SARS-CoV-2 infection in people with diabetes and obesity, while refining the therapeutic strategies and research priorities in this vulnerable population.

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Topics: Diabetes mellitus (50%)
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44 results found


Open accessPosted ContentDOI: 10.1101/2021.02.24.21251664
Raul Pellini, Aldo Venuti, Fulvia Pimpinelli, Elva Abril  +25 moreInstitutions (1)
26 Feb 2021-medRxiv
Abstract: Background The first goal of the study was to analyse the antibody titre 7 days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and BMI. Methods Participants were assigned to receive the priming dose at baseline and booster dose at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Findings 248 HWCs were analysed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7); was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p Interpretation These findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population. Although further studies are needed, this data may have important implications for the development of vaccination strategies for COVID-19, particularly in obese people. Funding None

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Topics: Booster dose (62%), Vaccination (53%)

24 Citations


Open accessJournal ArticleDOI: 10.1016/J.ECLINM.2021.100928
Raul Pellini, Aldo Venuti, Fulvia Pimpinelli, Elva Abril  +25 moreInstitutions (1)
04 Jun 2021-EClinicalMedicine
Abstract: Background Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. Methods An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. Findings 248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively). Interpretation 99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine. Funding None.

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Topics: Booster dose (56%), Vaccination (51%)

17 Citations


Open accessJournal ArticleDOI: 10.1038/S41598-021-88014-Z
16 Apr 2021-Scientific Reports
Abstract: Diabetes is associated with severe COVID-19 and mortality. The aim of the present study was to determine the effect of age on the association between diabetes and mortality in patients with laboratory-confirmed COVID-19 in Mexico. This retrospective cohort study involved patients aged 20 years or older with symptoms of viral respiratory disease who were screened for SARS-CoV-2 infection across the System of Epidemiological Surveillance of Viral Respiratory Disease in Mexico from January 1 through November 4, 2020. Cox proportional-hazard regression was used to calculate the hazard ratio for 28-day mortality and its 95% confidence interval (CI). Among 757,210 patients with COVID-19 (outpatients and inpatients), 120,476 (16%) had diabetes and 80,616 died. Among 878,840 patients without COVID-19 (those who tested negative for SARS-CoV-2 infection), 88,235 (10.0%) had diabetes and 20,134 died. Among patients with COVID-19, diabetes was associated with a hazard ratio for death of 1.49 (95% CI 1.47–1.52), adjusting for age, sex, smoking habit, obesity, hypertension, immunodeficiency, and cardiovascular, pulmonary, and chronic renal disease. The strength of the association decreased with age (trend test: P = 0.004). For example, the adjusted hazard ratio for death was 3.12 (95% CI 2.86–3.40) for patients 20–39 years of age; in contrast, the adjusted hazard ratio of death for patients 80 years of age or older was 1.11 (95% CI 1.06–1.16). The adjusted hazard ratios were 1.66 (95% CI 1.58–1.74) in outpatients and 1.14 (95% CI 1.12–1.16) in inpatients. In hospitalized patients 80 years of age or older, no association was observed between diabetes and COVID-19-related mortality (adjusted hazard ratio: 1.03; 95% CI 0.98–1.08). Among patients without COVID-19, the adjusted hazard ratio for death was 1.78 (95% CI 1.73–1.84). In conclusion, in adult patients with COVID-19 in Mexico, the risk of death associated with diabetes decreased with age. No association between diabetes and mortality was observed among inpatients 80 years of age or older. Our findings should be verified in other populations.

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10 Citations


Open accessJournal ArticleDOI: 10.1016/J.METABOL.2021.154814
Abstract: Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.

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Topics: Population (52%), Type 2 diabetes (51%), Diabetes mellitus (51%)

7 Citations


Open accessJournal ArticleDOI: 10.1016/J.REDOX.2021.101976
01 Jul 2021-Redox biology
Abstract: Mitochondria are central regulators of cellular metabolism, most known for their role in energy production. They can be "enhanced" by physical activity (including exercise), which increases their integrity, efficiency and dynamic adaptation to stressors, in short "mitochondrial fitness". Mitochondrial fitness is closely associated with cardiorespiratory fitness and physical activity. Given the importance of mitochondria in immune functions, it is thus not surprising that cardiorespiratory fitness is also an integral determinant of the antiviral host defense and vulnerability to infection. Here, we first briefly review the role of physical activity in viral infections. We then summarize mitochondrial functions that are relevant for the antiviral immune response with a particular focus on the current Coronavirus Disease (COVID-19) pandemic and on innate immune function. Finally, the modulation of mitochondrial and cardiorespiratory fitness by physical activity, aging and the chronic diseases that represent the most common comorbidities of COVID-19 is discussed. We conclude that a high mitochondrial - and related cardiorespiratory - fitness should be considered as protective factors for viral infections, including COVID-19. This assumption is corroborated by reduced mitochondrial fitness in many established risk factors of COVID-19, like age, various chronic diseases or obesity. We argue for regular analysis of the cardiorespiratory fitness of COVID-19 patients and the promotion of physical activity - with all its associated health benefits - as preventive measures against viral infection.

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5 Citations


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161 results found


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.6775
26 May 2020-JAMA
Abstract: Importance There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

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Topics: Interquartile range (55%), Respiratory virus (51%)

5,140 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2021436
Abstract: BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.)

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Topics: Lung injury (55%), Mechanical ventilation (52%), Randomized controlled trial (52%) ... read more

4,501 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2034577
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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4,222 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2007764
John H. Beigel1, Kay M. Tomashek1, Lori E. Dodd1, Aneesh K. Mehta1  +36 moreInstitutions (1)
Abstract: Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducte...

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3,423 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2521-4
08 Jul 2020-Nature
Abstract: Coronavirus disease 2019 (COVID-19) has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, and this requires new approaches for the timely analysis of large datasets. Working on behalf of NHS England, we created OpenSAFELY-a secure health analytics platform that covers 40% of all patients in England and holds patient data within the existing data centre of a major vendor of primary care electronic health records. Here we used OpenSAFELY to examine factors associated with COVID-19-related death. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59 (95% confidence interval 1.53-1.65)); greater age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors (HR 1.48 (1.29-1.69) and 1.45 (1.32-1.58), respectively). We have quantified a range of clinical factors associated with COVID-19-related death in one of the largest cohort studies on this topic so far. More patient records are rapidly being added to OpenSAFELY, we will update and extend our results regularly.

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Topics: Cohort study (53%), Hazard ratio (51%), Risk assessment (50%)

2,257 Citations


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202144