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1.
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
2.
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.

3.
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.

6.
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
7.
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
9.
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
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