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1.
Front Cardiovasc Med ; 8: 644095, 2021.
Article in English | MEDLINE | ID: covidwho-1268239

ABSTRACT

Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic ß-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern.

2.
Inflammopharmacology ; 29(4): 1001-1016, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1263162

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19.


Subject(s)
COVID-19/immunology , COVID-19/prevention & control , Dietary Supplements , Immune System/immunology , Micronutrients/administration & dosage , Minerals/administration & dosage , Vitamins/administration & dosage , Humans , Immune System/drug effects
3.
Diabet Med ; 38(2): e14458, 2021 02.
Article in English | MEDLINE | ID: covidwho-1214788

ABSTRACT

Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/epidemiology , Overweight/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Drug Therapy, Combination , Glucosides/therapeutic use , Glycosides/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Overweight/complications , Practice Guidelines as Topic , United Kingdom
4.
Arch Bronconeumol (Engl Ed) ; 2021 Mar 26.
Article in English, Spanish | MEDLINE | ID: covidwho-1193221

ABSTRACT

Pulmonary involvement in COVID-19 is frequently associated with alterations in oxygenation. The arterial partial pressure of oxygen (PaO2) is the most clinically used variable to assess such oxygenation, since it decisively influences the oxygen transported by hemoglobin (expressed by its percentage of saturation, SaO2). However, two recent studies conducted respectively in silico and using omic techniques in red blood cells of COVID-19 patients have suggested that SARS-CoV-2 could decrease the affinity of oxygen for the hemoglobin (which would imply that PaO2 would overestimate SaO2), and also reduce the amount of this carrier molecule. OBJECTIVE: To evaluate this hypothesis in blood samples from COVID-19 patients. METHODS: Blood gases of all COVID-19 patients performed in our laboratory in two months were included, as well as those from two control groups: synchronous patients with negative PCR for SARS-CoV-2 (SCG) and a historical group (HCG). Both SaO2 and venous saturations (SvO2) measured by cooximetry (COX) were compared separately with those calculated using the Kelman (K), Severinghaus (SV) and Siggaard-Andersen (SA) equations in each group. RESULTS: Measured and calculated SaO2 and SvO2 were practically equivalent in all groups. Intraclass correlation coefficients (ICC) for SaO2 in COVID-19 were 0.993 for COX-K and 0.992 for both COX-SV and COX-SA; being 0.995 for SvO2 for either COX-K, COX-SV or COX-SA. Hemoglobin and ferritin were slightly higher in COVID-19 compared to SCG and HCG (hemoglobin, p < 0.001 for both; ferritin, p < 0.05 for SCG and p < 0.001 for HCG). CONCLUSION: Under clinical conditions SARS-CoV-2 does not have an appreciable influence on the affinity of oxygen for the hemoglobin, nor on the levels of this carrier molecule. Therefore, PaO2 is a good marker of blood oxygenation also in COVID-19.

5.
PLoS One ; 16(3): e0246087, 2021.
Article in English | MEDLINE | ID: covidwho-1133680

ABSTRACT

AIM: To identify laboratory biomarkers that predict disease severity and outcome among COVID-19 patients admitted to the Millennium COVID-19 Care Center in Ethiopia. METHODS: A retrospective cohort study was conducted among 429 COVID-19 patients who were on follow up from July to October 2020. Data was described using frequency tables. Robust Poisson regression model was used to identify predictors of COVID-19 severity where adjusted relative risk (ARR), P-value and 95 CI for ARR were used to test significance. Binary Logistic regression model was used to assess the presence of statistically significant association between the explanatory variables and COVID-19 outcome where adjusted odds ratio (AOR), P-value and 95%CI for AOR were used for testing significance. RESULTS: Among the 429 patients studied, 182 (42.4%) had Severe disease at admission and the rest 247 (57.6%) had Non-severe disease. Regarding disease outcome, 45 (10.5%) died and 384 (89.5%) were discharged alive. Age group (ARR = 1.779, 95%CI = 1.405-2.252, p-value <0.0001), Neutrophil to Lymphocyte ratio (NLR) (ARR = 4.769, 95%CI = 2.419-9.402 p-value <0.0001), Serum glutamic oxaloacetic transaminase (SGOT) (ARR = 1.358, 95%CI = 1.109-1.662 p-value = 0.003), Sodium (ARR = 1.321, 95%CI = 1.091-1.600 p-value = 0.004) and Potassium (ARR = 1.269, 95%CI = 1.059-1.521 p-value = 0.010) were found to be significant predictors of COVID-19 severity. The following factors were significantly associated with COVID-19 outcome; age group (AOR = 2.767, 95%CI = 1.099-6.067, p-value = 0.031), white blood cell count (WBC) (AOR = 4.253, 95%CI = 1.918-9.429, p-value = 0.0001) and sodium level (AOR = 3.435, 95%CI = 1.439-8.198, p-value = 0.005). CONCLUSIONS: Assessing and monitoring the laboratory markers of WBC, NLR, SGOT, sodium and potassium levels at the earliest stage of the disease could have a considerable role in halting disease progression and death.


Subject(s)
Biomarkers/analysis , COVID-19/pathology , Severity of Illness Index , Adolescent , Adult , Age Factors , Aspartate Aminotransferases/blood , COVID-19/virology , Comorbidity , Developing Countries , Female , Humans , Logistic Models , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Odds Ratio , Retrospective Studies , SARS-CoV-2/isolation & purification , Young Adult
6.
Br J Clin Pharmacol ; 87(10): 3643-3646, 2021 10.
Article in English | MEDLINE | ID: covidwho-1121364

ABSTRACT

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.


Subject(s)
COVID-19 , Diabetes Mellitus , Sodium-Glucose Transporter 2 Inhibitors , Blood Glucose , Glucose , Humans , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
7.
Crit Care Med ; 49(2): e179-e190, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-947682

ABSTRACT

OBJECTIVES: Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose sodium ascorbate in sepsis. DESIGN: Interventional study. SETTING: Research Institute. SUBJECTS: Adult Merino ewes. INTERVENTIONS: Sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg). MEASUREMENTS AND MAIN RESULTS: Sepsis-induced fever (41.4 ± 0.2°C; mean ± se), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial Po2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue Po2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01). Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary Po2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg). We confirmed these physiologic findings in a coronavirus disease 2019 patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours. CONCLUSIONS: IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.


Subject(s)
Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Escherichia coli Infections/drug therapy , Sepsis/drug therapy , Animals , Bacteremia/drug therapy , Disease Models, Animal , Dose-Response Relationship, Drug , Sheep
9.
Function (Oxf) ; 1(2): zqaa024, 2020.
Article in English | MEDLINE | ID: covidwho-817406

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic remains a serious public health problem and will continue to be until effective drugs and/or vaccines are available. The rational development of drugs critically depends on our understanding of disease mechanisms, that is, the physiology and pathophysiology underlying the function of the organ targeted by the virus. Since the beginning of the pandemic, tireless efforts around the globe have led to numerous publications on the virus, its receptor, its entry into the cell, its cytopathic effects, and how it triggers innate and native immunity but the role of apical sodium transport mediated by the epithelial sodium channel (ENaC) during the early phases of the infection in the airways has received little attention. We propose a pathophysiological model that defines the possible role of ENaC in this process.

10.
Cureus ; 12(8): e10054, 2020 Aug 26.
Article in English | MEDLINE | ID: covidwho-808939

ABSTRACT

Background and objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. The disease mainly affects the respiratory system of the patient, in particular, the lungs, which leads to patients presenting with acute respiratory distress syndrome and acute respiratory failure, with 5-15% of patients requiring observation in the intensive care unit (ICU) with respiratory support in the form of ventilation. This study was aimed at identifying the role of biochemical markers in the risk stratification of invasive and non-invasive ventilation of hospitalized COVID-19 patients. Materials and methods The study was conducted as a prospective, observational study of all admitted COVID-19 patients. A comparative analysis was performed of the survivors who were on invasive versus (vs) non-invasive ventilation and the non-survivors similarly. After computing the descriptive statistics, a multinomial logistic regression model was applied to obtain an unadjusted odds ratio (OR) at 95% confidence interval (CI), with Hosmer-Lemeshow (HL) goodness-of-fit test used to predict the fitness of the data. Kaplan-Meier survival curves were obtained for each of the laboratory investigations predicting survival along with the intensive care stay and invasive ventilation. A log-rank test was carried out to compare the survival distributions. Results A total of 373 included patients in the study had a mean age of 52.78 ± 15.76 years with females younger than males, and indifference amongst invasive vs non-invasively ventilated (p=0.821). Females were slightly more prone to invasive ventilation (p=0.097). Overall, 39% of the subjects did not need respiratory support, while 13% were on a ventilator, 16% on bilevel positive airway pressure/continuous positive airway pressure (BiPAP/CPAP), and 31% on supplemental oxygen therapy. Among the laboratory markers, mean hemoglobin was evidently lower in the invasive group, leukocytosis and thrombocytopenia were present in both invasively ventilated and non-surviving patients, while neutrophilia and lymphocytopenia were statistically indifferent among the mode of ventilation. Elevated urea, creatinine, and sodium were also significantly deranged laboratory markers amongst the invasively ventilated group. C-reactive protein (CRP) and lactate dehydrogenase (LDH) were elevated significantly in the invasive group, while serum ferritin was more frequently raised in the non-invasively ventilated group. Procalcitonin (PCT) was significantly associated with invasive ventilation as opposed to the non-invasive group. D-dimer was equally raised in both the groups at admission but significantly elevated in the invasive group at discharge. A multinomial regression model signified D-dimer (OR: 16.301), hypernatremia (OR: 12.738), creatinine (OR: 12.589), urea (OR: 12.576), and LDH (OR: 12.245) most significantly associated with death, while those for invasive ventilation were D-dimer (OR: 8.744), hypernatremia (OR: 4.532), PCT (OR: 3.829), neutrophilia (OR: 3.804), leukocytosis (OR: 3.330), and serum urea (OR: 3.312). Kaplan-Meier curves conclude total leucocyte count (TLC), neutrophils, lymphocytes, urea, creatinine, sodium, CRP, LDH, PCT, and D-dimer all significantly contributing to an early death. Conclusion The most significant marker for mortality was D-dimer, followed by serum sodium, urea/creatinine, LDH, ICU stay, and invasive ventilation.

11.
Elife ; 92020 05 26.
Article in English | MEDLINE | ID: covidwho-378182

ABSTRACT

Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.


Viruses hijack the cellular machinery of humans to infect their cells and multiply. The virus causing the global COVID-19 pandemic, SARS-CoV-2, is no exception. Identifying which proteins in human cells the virus co-opts is crucial for developing new ways to diagnose, prevent and treat COVID-19 infections. SARS-CoV-2 is covered in spike-shaped proteins, which the virus uses to gain entry into cells. First, the spikes bind to a protein called ACE2, which is found on the cells that line the respiratory tract and lungs. SARS-CoV-2 then exploits enzymes called proteases to cut, or cleave, its spikes at a specific site which allows the virus to infiltrate the host cell. Proteases identify which proteins to target based on the sequence of amino acids ­ the building blocks of proteins ­ at the cleavage site. However, it remained unclear which human proteases SARS-CoV-2 co-opts and whether its cut site is similar to human proteins. Now, Anand et al. show that the spike proteins on SARS-CoV-2 may have the same sequence of amino acids at its cut site as a human epithelial channel protein called ENaC-α. This channel is important for maintaining the balance of salt and water in many organs including the lungs. Further analyses showed that ENaC-α is often found in the same types of human lung and respiratory tract cells as ACE2. This suggests that SARS-CoV-2 may use the same proteases that cut ENaC-α to get inside human respiratory cells. It is possible that by hijacking the cutting mechanism for ENaC-α, SARS-CoV-2 interferes with the balance of salt and water in the lungs of COVID-19 patients. This may help explain why the virus causes severe respiratory symptoms. However, more studies are needed to confirm that the proteases that cut ENaC-α also cut the spike proteins on SARS-CoV-2, and how this affects the respiratory health of COVID-19 patients.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/virology , Epithelial Sodium Channels/metabolism , Molecular Mimicry , Peptide Hydrolases/metabolism , Pneumonia, Viral/virology , Viral Envelope Proteins/metabolism , Viral Proteins/metabolism , Angiotensin-Converting Enzyme 2 , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , Epithelial Sodium Channels/genetics , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Proteolysis , SARS-CoV-2 , Substrate Specificity , Viral Envelope Proteins/genetics , Viral Proteins/genetics
12.
Ann Clin Biochem ; 57(3): 262-265, 2020 05.
Article in English | MEDLINE | ID: covidwho-215069

ABSTRACT

BACKGROUND: Early studies have reported various electrolyte abnormalities at admission in patients who progress to the severe form of coronavirus disease 2019 (COVID-19). As electrolyte imbalance may not only impact patient care, but provide insight into the pathophysiology of COVID-19, we aimed to analyse all early data reported on electrolytes in COVID-19 patients with and without severe form. METHODS: An electronic search of Medline (PubMed interface), Scopus and Web of Science was performed for articles comparing electrolytes (sodium, potassium, chloride and calcium) between COVID-19 patients with and without severe disease. A pooled analysis was performed to estimate the weighted mean difference (WMD) with 95% confidence interval. RESULTS: Five studies with a total sample size of 1415 COVID-19 patients. Sodium was significantly lower in patients with severe COVID-19 (WMD: -0.91 mmol/L [95% CI: -1.33 to -0.50 mmol/L]). Similarly, potassium was also significantly lower in COVID-19 patients with severe disease (WMD: -0.12 mmol/L [95% CI: -0.18 to -0.07 mmol/L], I2=33%). For chloride, no statistical differences were observed between patients with severe and non-severe COVID-19 (WMD: 0.30 mmol/L [95% CI: -0.41 to 1.01 mmol/L]). For calcium, a statistically significant lower concentration was noted in patients with severe COVID-19 (WMD: -0.20 mmol/L [95% CI: -0.25 to -0.20 mmol/L]). CONCLUSIONS: This pooled analysis confirms that COVID-19 severity is associated with lower serum concentrations of sodium, potassium and calcium. We recommend electrolytes be measured at initial presentation and serially monitored during hospitalization in order to establish timely and appropriate corrective actions.


Subject(s)
Coronavirus Infections/blood , Electrolytes/blood , Pneumonia, Viral/blood , Betacoronavirus , COVID-19 , Calcium/blood , Chlorides/blood , Coronavirus Infections/physiopathology , Humans , Pandemics , Pneumonia, Viral/physiopathology , Potassium/blood , SARS-CoV-2 , Sodium/blood , Water-Electrolyte Balance
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