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1.
J Pharmacol Exp Ther ; 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1909559

ABSTRACT

We hypothesized that exosomal microRNAs (miRNAs) could be implied in the pathogenesis of thromboembolic complications in COVID-19. We isolated circulating exosomes from COVID-19 patients and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-Dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for SARS-CoV-2 internalization, including ACE2, TMPRSS2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared to cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19. Significance Statement In this work, we demonstrate for the first time that two specific microRNA (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. Our findings are especially relevant to the general audience when considering the emerging prominence of post-acute sequelae of COVID-19 systemic manifestations known as Long-COVID.

2.
Nat Commun ; 13(1): 2318, 2022 04 28.
Article in English | MEDLINE | ID: covidwho-1815536

ABSTRACT

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p < 0.001). The comparison of patients with poor and good glycaemic control through Cox regression also show an increased risk for patients with poor control (adjusted hazard ratio [HR], 0.261; 95% CI, 0.097-0.700; p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p < 0.001) and sex (HR = 0.105, CI 0.035-0.317 for females; p < 0.001) are significantly associated with the incidence of breakthrough infections.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Female , Glycated Hemoglobin A , Glycemic Control , Humans , RNA, Messenger , SARS-CoV-2
3.
J Clin Med ; 11(6)2022 Mar 12.
Article in English | MEDLINE | ID: covidwho-1742504

ABSTRACT

BACKGROUND/AIMS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded single-stranded RNA virus, a member of the subgenus Sarbecovirus (beta-CoV lineage B) and responsible for the coronavirus disease 2019 (COVID-19). COVID-19 encompasses a large range of disease severity, from mild symptoms to severe forms with Intensive Care Unit admission and eventually death. The severe forms of COVID-19 are usually observed in high-risk patients, such as those with type two diabetes mellitus. Here, we review the available evidence linking acute and chronic hyperglycemia to COVID-19 outcomes, describing also the putative mediators of such interactions. FINDINGS/CONCLUSIONS: Acute hyperglycemia at hospital admission represents a risk factor for poor COVID-19 prognosis in patients with and without diabetes. Acute and chronic glycemic control are both emerging as major determinants of vaccination efficacy, disease severity and mortality rate in COVID-19 patients. Mechanistically, it has been proposed that hyperglycemia might be a disease-modifier for COVID-19 through multiple mechanisms: (a) induction of glycation and oligomerization of ACE2, the main receptor of SARS-CoV-2; (b) increased expression of the serine protease TMPRSS2, responsible for S protein priming; (c) impairment of the function of innate and adaptive immunity despite the induction of higher pro-inflammatory responses, both local and systemic. Consistently, managing acute hyperglycemia through insulin infusion has been suggested to improve clinical outcomes, while implementing chronic glycemic control positively affects immune response following vaccination. Although more research is warranted to better disentangle the relationship between hyperglycemia and COVID-19, it might be worth considering glycemic control as a potential route to optimize disease prevention and management.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329936

ABSTRACT

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. To explore the association between glycaemic control and immune responses or breakthrough infections in patients with T2D after mRNA-BNT162b2 vaccination, we conducted a prospective observational study among healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy). Patients were followed for one year (5 visits) after one full vaccination cycle to evaluate immune responses and monitor the incidence of breakthrough infections. The one-year mean of HbA1c values and canonical risk factors were used to estimate their association with breakthrough infections through Cox regression models adjusted for multiple variables. Overall, 494 subjects were followed up for 346 ± 49 days and completed the study. Patients with good glycaemic control (HbA1c one-year mean < 7%) showed a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). One-year mean of HbA1c was significantly associated with the incidence of breakthrough infections (adjusted hazard ratio [HR], 0.285;95% confidence interval [CI], 0.106 to 0.768;p = 0.013). Among other factors, only smoking status was associated with the incidence of breakthrough infections (HR = 0.360, CI 0.181–0.716 for non-smokers). In summary, poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320770

ABSTRACT

The symptoms most commonly reported by patients affected by coronavirus disease 2019 (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g. high blood pressure, thrombosis, pulmonary embolism) seem to suggest that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ of COVID-19.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316455

ABSTRACT

Background: . The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons have been equal to that of symptomatic patients, suggesting a similar risk for endothelial dysfunction and increased coagulation in asymptomatic and symptomatic patients. To date, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. We evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial lush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. Methods: . This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. Results: . Thrombus dimensions were significantly higher in ASAP patients as compared to SANE patients. Interestingly, 39 (84.9%) of ASAP patients also had thrombus specimens positive for SARS-COV-2. In ASAP STEMI patients (n=46), thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p<0.005). MBG and left ventricular function were significantly lower in ASAP STEMI patients (p<0.001). Multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Conclusions: . In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

9.
PLoS One ; 16(9): e0256903, 2021.
Article in English | MEDLINE | ID: covidwho-1406751

ABSTRACT

INTRODUCTION: During COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality. METHODS: COVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020. RESULTS: 618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome. DISCUSSION: COVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Aged , COVID-19/epidemiology , Female , Hospital Mortality , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Respiratory Therapy , Retrospective Studies
10.
Crit Care ; 25(1): 217, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1388810

ABSTRACT

BACKGROUND: The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. METHODS: This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. RESULTS: In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05). Interestingly, ASAP vs. SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2. After PPCI, a MBG 2-3 was present in only 26.1% of ASAP vs. 97.7% of SANE STEMI patients (p < 0.001). Notably, death and nonfatal AMI were higher in ASAP vs. SANE patients (p < 0.05). Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005). Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs. 30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001). ASAP vs. SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001). CONCLUSIONS: In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.


Subject(s)
COVID-19/complications , Coronary Thrombosis/virology , Heart/physiopathology , Microcirculation/physiology , Myocardial Infarction/physiopathology , Aged , Analysis of Variance , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Cohort Studies , Coronary Angiography/methods , Coronary Thrombosis/epidemiology , Echocardiography/methods , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology
11.
Cardiovasc Diabetol ; 20(1): 99, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1219133

ABSTRACT

RATIONALE: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. OBJECTIVE: To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. METHODS AND RESULTS: We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. CONCLUSIONS: The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/metabolism , Diabetes Mellitus/metabolism , Myocytes, Cardiac/metabolism , SARS-CoV-2/metabolism , Aged , Amino Acid Sequence , Autopsy , COVID-19/epidemiology , COVID-19/pathology , Cohort Studies , Diabetes Mellitus/pathology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Myocytes, Cardiac/pathology , Protein Binding/physiology , Protein Structure, Secondary
12.
PLoS One ; 15(12): e0243700, 2020.
Article in English | MEDLINE | ID: covidwho-966684

ABSTRACT

BACKGROUND: Italy has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory. OBJECTIVES: Aim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy). METHODS: COVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission. RESULTS: Among 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42-4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39-14.46; p<0.001) and malignancies (OR 2.62, 95%CI 1.21-5.68; p = 0.015) disclosed an independent association with a poor prognosis, Glasgow Coma Scale (GCS) and Respiratory Severity Scale allowed to identify at higher mortality risk. Sensitivity analysis further enhanced these findings. CONCLUSION: Mortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage.


Subject(s)
COVID-19/epidemiology , Liver Diseases/epidemiology , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Chronic Disease , Comorbidity , Female , Hospital Mortality , Hospitalization , Humans , Italy/epidemiology , Liver Diseases/diagnosis , Liver Diseases/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2/isolation & purification
13.
BMC Cardiovasc Disord ; 20(1): 373, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-714180

ABSTRACT

BACKGROUND: Hypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19. METHODS: In this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events. RESULTS: Patients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p < 0.05). Furthermore, patients in non-0 vs. 0 blood group had higher rate of cardiac injury (10 (13.9%) vs. 27 (29.3%)) and death, (6 (8.3%) vs. 18 (19.6%)), (p < 0.05). At the multivariate analysis, Interleukin-6 (1.118, CI 95% 1.067-1.171) and non-0 blood group (2.574, CI 95% 1.207-5.490) were independent predictors of cardiac injury in hypertensive patients with covid-19. D-dimer (1.082, CI 95% 1.027-1.140), Interleukin-6 (1.216, CI 95% 1.082-1.367) and non-0 blood group (3.706, CI 95% 1.223-11.235) were independent predictors of deaths events in hypertensive patients with covid-19. CONCLUSIONS: Taken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.


Subject(s)
ABO Blood-Group System , Betacoronavirus/pathogenicity , Blood Pressure , Coronavirus Infections/blood , Hypertension/blood , Pneumonia, Viral/blood , Adult , Aged , Biomarkers/blood , Blood Coagulation , Blood Coagulation Factors/analysis , COVID-19 , Case-Control Studies , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Host-Pathogen Interactions , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Inflammation Mediators/blood , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prospective Studies , Risk Factors , SARS-CoV-2
15.
J Am Heart Assoc ; 9(17): e016948, 2020 09.
Article in English | MEDLINE | ID: covidwho-635173

ABSTRACT

BACKGROUND Coronavirus disease 2019 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin-converting enzyme 2 in humans. Thus, patients with hypertension with COVID-19 could have worse prognosis. Indeed, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers may interfere with angiotensin-converting enzyme 2 expression/activity. Thus, patients with hypertension undergoing angiotensin-converting enzyme inhibitor and/or angiotensin receptor blockers drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of angiotensin-converting enzyme inhibitor versus angiotensin receptor blockers versus calcium channel blockers on clinical outcomes as mechanical ventilation, intensive care unit admissions, heart injury, and death in 62 patients with hypertension hospitalized for COVID-19 infection. METHODS AND RESULTS The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania "Luigi Vanvitelli" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania "Luigi Vanvitelli," Naples, and at General Medical Assistance Unit "FIMG," Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142, 1.008-1.294, P<0.05), while highest values of interleukin-6 predicted the admission to intensive care unit (1.617, 1.094-2.389), mechanical ventilation (1.149, 1.082-1.219), heart injuries (1.367, 1.054-1.772), and deaths (4.742, 1.788-8.524). CONCLUSIONS Anti-hypertensive drugs didn't affect the prognosis in patients with COVID-19. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in patients with hypertension with COVID-19 infection.


Subject(s)
Antihypertensive Agents/therapeutic use , Betacoronavirus , Blood Pressure/physiology , Coronavirus Infections/complications , Hypertension/drug therapy , Pneumonia, Viral/complications , COVID-19 , Coronavirus Infections/epidemiology , Female , Humans , Hypertension/complications , Hypertension/physiopathology , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Prognosis , Prospective Studies , SARS-CoV-2
16.
Cardiovasc Diabetol ; 19(1): 76, 2020 06 11.
Article in English | MEDLINE | ID: covidwho-593567

ABSTRACT

A possible association could exist between type 2 diabetes mellitus (T2DM) and Coronavirus-19 (Covid-19) infection. Indeed, patients with T2DM show high prevalence, severity of disease and mortality during Covid-19 infection. However, the rates of severe disease are significantly higher in patients with diabetes compared with non-diabetes (34.6% vs. 14.2%; p < 0.001). Similarly, T2DM patients have higher rates of need for Intensive Care Unit (ICU, 37.0% vs. 26.7%; p = 0.028). Thus, about the pneumonia of Covid-19, we might speculate that the complicated alveolar-capillary network of lungs could be targeted by T2DM micro-vascular damage. Therefore, T2DM patients frequently report respiratory symptoms and are at increased risk of several pulmonary diseases. In addition, pro-inflammatory pathways as that involving interleukin 6 (IL-6), could be a severity predictor of lung diseases. Therefore, it looks intuitive to speculate that this condition could explain the growing trend of cases, hospitalization and mortality for patients with T2DM during Covid-19 infection. To date, an ongoing experimental therapy with monoclonal antibody against the IL-6 receptor in Italy seems to have beneficial effects on severe lung disease and prognosis in patients with Covid-19 infection. Therefore, should patients with T2DM be treated with more attention to glycemic control and monoclonal antibody against the IL-6 receptor during the Covid-19 infection?


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/metabolism , Blood Glucose/metabolism , Coronavirus Infections/blood , Diabetes Mellitus, Type 2/blood , Pneumonia, Viral/blood , Antibodies, Monoclonal, Humanized/pharmacology , Blood Glucose/drug effects , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glycemic Index/drug effects , Glycemic Index/physiology , Humans , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Receptors, Interleukin-6/antagonists & inhibitors , Receptors, Interleukin-6/blood , SARS-CoV-2 , Treatment Outcome
17.
Diabetes Care ; 43(7): 1408-1415, 2020 07.
Article in English | MEDLINE | ID: covidwho-324249

ABSTRACT

OBJECTIVE: An important prognostic factor in any form of infection seems to be glucose control in patients with type 2 diabetes. There is no information about the effects of tight glycemic control on coronavirus disease 2019 (COVID-19) outcomes in patients with hyperglycemia. Therefore, we examined the effects of optimal glycemic control in patients with hyperglycemia affected by COVID-19. RESEARCH DESIGN AND METHODS: Fifty-nine patients with COVID-19 hospitalized with moderate disease were evaluated. On the basis of admission glycemia >7.77 mmol/L, patients were divided into hyperglycemic and normoglycemic groups. Interleukin 6 (IL-6) and D-dimer levels were evaluated at admission and weekly during hospitalization. The composite end point was severe disease, admission to an intensive care unit, use of mechanical ventilation, or death. RESULTS: Thirty-four (57.6%) patients were normoglycemic and 25 (42.4%) were hyperglycemic. In the hyperglycemic group, 7 (28%) and 18 (72%) patients were diagnosed with diabetes already before admission, and 10 (40%) and 15 (60%) were treated without and with insulin infusion, respectively. The mean of glycemia during hospitalization was 10.65 ± 0.84 mmol/L in the no insulin infusion group and 7.69 ± 1.85 mmol/L in the insulin infusion group. At baseline, IL-6 and D-dimer levels were significantly higher in the hyperglycemic group than in the normoglycemic group (P < 0.001). Even though all patients were on standard treatment for COVID-19 infection, IL-6 and D-dimer levels persisted higher in patients with hyperglycemia during hospitalization. In a risk-adjusted Cox regression analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than those without diabetes and with normoglycemia. Cox regression analysis evidenced that patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion. CONCLUSIONS: Insulin infusion may be an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Hyperglycemia/drug therapy , Hyperglycemia/epidemiology , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Pneumonia, Viral/epidemiology , Blood Glucose/metabolism , COVID-19 , Coronavirus Infections/drug therapy , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , SARS-CoV-2
18.
J Clin Med ; 9(5)2020 May 11.
Article in English | MEDLINE | ID: covidwho-232618

ABSTRACT

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

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