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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311207

ABSTRACT

Background: The need to rapidly immunize the population against SARS-CoV-2 to obtain herd immunity together with shortage of vaccine supplies suggest to vaccinate the largest number of people with a single dose of vaccine delaying the second dose.Methods: The primary outcomes of our meta-analysis were the efficacy of one or both doses of vaccines in preventing COVID-19 and their safety. In addition, using a differential equation model taking into account the effects of lockdown and vaccination, we sought to study the effectiveness of one or both doses of vaccines in preventing new cases of COVID-19 in UK and Israel. These countries, where a large portion of the population is already vaccinated, have different vaccination strategies, 3 vs. 12 weeks delay between first and second dose.Findings: The first vaccine dose averted infection in 71% of participants, while the booster dose cumulatively prevented COVID-19 in 87% of participants. The pooled treatment effects in two age subgroups (<65 or ≥65 years) were not significantly different. No significant difference on efficacy between white and black or ethnic minorities was observed. Mortality was reduced by 56% after active treatment versus placebo. The pooled Risk-Ratio of experiencing a serious event after vaccination was 6%.Population data modelling show a dramatic reduction of the number of daily new cases in UK starting at 16 days after the first dose administration. Notably, the number of dose-1 daily administrations explains the observed reduction of daily new cases in UK and is able to predict new observations with high certainty. In Israel, the effects of the first dose of vaccine in reducing the incidence of COVID-19 was virtually immediate. Interpretation: Our RCT meta-analysis and population-based analysis show that the first dose of COVID-19 vaccines averts infection in almost 3/4 of subjects and suggest that postponing the second dose by at least 12 weeks is a suitable strategy that allows vaccinating more people, substantially increasing the benefits of vaccines.Funding Statement: There was no external funding source for this study.Declaration of Interests: All authors declare no competing interests: no support from any organisation for the submitted work;no financial relationships with any organisations that might have an interest in the submitted work;no other relationships or activities that could appear to have influenced the submitted work.

2.
Lancet Diabetes Endocrinol ; 10(3): 221-230, 2022 03.
Article in English | MEDLINE | ID: covidwho-1665596

ABSTRACT

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.


Subject(s)
COVID-19 , Health Status Disparities , Sex Characteristics , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Hypothalamo-Hypophyseal System , Male , Pituitary-Adrenal System , Public Health
3.
Comput Struct Biotechnol J ; 19: 6080-6089, 2021.
Article in English | MEDLINE | ID: covidwho-1664834

ABSTRACT

Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.

4.
Lancet Diabetes Endocrinol ; 9(11): 786-798, 2021 11.
Article in English | MEDLINE | ID: covidwho-1586178

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Disease Management , Metabolic Diseases/epidemiology , Metabolic Diseases/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/metabolism , Diabetes Mellitus/therapy , Humans , Hypertension/epidemiology , Hypertension/metabolism , Hypertension/therapy , Metabolic Diseases/therapy , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/therapy , Obesity/epidemiology , Obesity/metabolism , Obesity/therapy
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292939

ABSTRACT

The COVID-19 data catalogue is a repository that provides a landscape view of COVID-19 studies and datasets as a putative source to enable researchers to develop personalized COVID-19 predictive risk models. The COVID-19 data catalogue currently contains over 400 studies and their relevant information collected from a wide range of global sources such as global initiatives, clinical trial repositories, publications and data repositories. Further, the curated content stored in this data catalogue is complemented by a web application, providing visualizations of these studies, including their references, relevant information such as measured variables, and the geographical locations of where these studies were performed. This resource is one of the first to capture, organize and store studies, datasets and metadata in the area of COVID-19 in a comprehensive repository. We are convinced that our work will facilitate future research and development of personalized predictive risk models of COVID-19.

6.
Front Endocrinol (Lausanne) ; 12: 741248, 2021.
Article in English | MEDLINE | ID: covidwho-1526766

ABSTRACT

Background: Hyperglycemia and obesity are associated with a worse prognosis in subjects with COVID-19 independently. Their interaction as well as the potential modulating effects of additional confounding factors is poorly known. Therefore, we aimed to identify and evaluate confounding factors affecting the prognostic value of obesity and hyperglycemia in relation to mortality and admission to the intensive care unit (ICU) due to COVID-19. Methods: Consecutive patients admitted in two Hospitals from Italy (Bologna and Rome) and three from Spain (Barcelona and Girona) as well as subjects from Primary Health Care centers. Mortality from COVID-19 and risk for ICU admission were evaluated using logistic regression analyses and machine learning (ML) algorithms. Results: As expected, among 3,065 consecutive patients, both obesity and hyperglycemia were independent predictors of ICU admission. A ML variable selection strategy confirmed these results and identified hyperglycemia, blood hemoglobin and serum bilirubin associated with increased mortality risk. In subjects with blood hemoglobin levels above the median, hyperglycemic and morbidly obese subjects had increased mortality risk than normoglycemic individuals or non-obese subjects. However, no differences were observed among individuals with hemoglobin levels below the median. This was particularly evident in men: those with severe hyperglycemia and hemoglobin concentrations above the median had 30 times increased mortality risk compared with men without hyperglycemia. Importantly, the protective effect of female sex was lost in subjects with increased hemoglobin levels. Conclusions: Blood hemoglobin substantially modulates the influence of hyperglycemia on increased mortality risk in patients with COVID-19. Monitoring hemoglobin concentrations seem of utmost importance in the clinical settings to help clinicians in the identification of patients at increased death risk.


Subject(s)
COVID-19/mortality , Glycated Hemoglobin A/analysis , Hyperglycemia/epidemiology , Obesity, Morbid/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/epidemiology , Comorbidity , Female , Hospital Mortality , Humans , Hyperglycemia/blood , Incidence , Italy , Male , Middle Aged , Obesity, Morbid/blood , Prognosis , Retrospective Studies , Risk , Sex Factors , Spain , Survival Rate
7.
Computational and structural biotechnology journal ; 2021.
Article in English | EuropePMC | ID: covidwho-1505373

ABSTRACT

Graphical abstract Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n=469), jejunum (n=30), and colon (n=37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.

13.
Lancet Diabetes Endocrinol ; 8(7): 640-648, 2020 07.
Article in English | MEDLINE | ID: covidwho-197827

ABSTRACT

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.


Subject(s)
Bariatric Surgery/methods , Betacoronavirus , Coronavirus Infections/surgery , Obesity/surgery , Pandemics , Pneumonia, Viral/surgery , Postoperative Care/methods , Bariatric Surgery/trends , COVID-19 , Coronavirus Infections/epidemiology , Disease Management , Humans , Obesity/epidemiology , Pneumonia, Viral/epidemiology , Postoperative Care/trends , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , SARS-CoV-2
14.
Lancet Diabetes Endocrinol ; 8(6): 546-550, 2020 06.
Article in English | MEDLINE | ID: covidwho-108776

ABSTRACT

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/physiopathology , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Pandemics , Pneumonia, Viral/physiopathology , COVID-19 , Comorbidity , Contraindications, Drug , Coronavirus Infections/therapy , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Humans , Hypoglycemic Agents/administration & dosage , Multiple Organ Failure/chemically induced , Multiple Organ Failure/physiopathology , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2
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