The new coronavirus outbreak is an ongoing pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new coronavirus SARS-Cov-2 belongs to the subfamily of ...β–coronaviruses and shares 79.5% of the genetic sequence of SARS-CoV, the causative agent of the epidemic that started in 2002 and ended in 2004.
Considering the clinical impact of the new outbreak, it is highly important to study the potential responses of the human immune system during the SARS-CoV-2 infection as well as the role of virus-specific T cells and by B-lymphocytes. Moreover, specific data on the production of IgG and IgM is crucial to allow the rapid identification of the infection. In this paper we also described the importance of sensitive and specific rapid test for SARS-CoV-2. Indeed, this test represents an important immunological tool aimed at identifying the precise phase of the infection in order to undertake a more appropriate pharmacological treatment. Lastly, we provided an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2.
Since December 2019 SARS‐Cov‐2 was found responsible for the disease COVID‐19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID‐19. Drug ...repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID‐19, focusing on their antiviral, immune‐modulatory and/or anti‐inflammatory actions. Where available, data from clinical trials involving patients with COVID‐19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID‐19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID‐19 and reducing its symptoms and complications.
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This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a ...meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes.
We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA
, proportion of patients at HbA
target ≤7% (53 mmol/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI.
We identified 26 RCTs, lasting 12-52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA
(WMD = -0.47%, 95% CI -0.59 to -0.35), more patients at HbA
target (RR = 1.65, 95% CI 1.44-1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93-1.39) and a reduction in weight (WMD = -2.5 kg, 95% CI -3.3 to -1.7), with high heterogeneity (
> 89%,
< 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46-0.93) and reduced weight (WMD = -4.7 kg, 95% CI -6.9 to -2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA
WMD = -0.56%, 95% CI -0.72 to -0.40).
GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability.
We aimed to perform an analysis of individual case safety reports retrieved after the Standardized MedDRA Query "Pregnancy and neonatal topics" for which Direct-Acting Oral Anticoagulants (DOACs) ...were claimed as suspected/interacting drugs. Additionally, to investigate if exists a disproportion of cases reporting "Pregnancy and neonatal topics" adverse events rather than other adverse events for DOACs in comparison with all other drugs registered in VigiBase or warfarin. VigiBase, the World Health Organization (WHO)'s global database of individual case safety reports was used as data source. Forty-two cases of abortion were detected of which 18 (42.8%) had alternative causes for its occurrence. Fourteen cases reported congenital anomaly (8 cases) or low birth weight baby/fetal growth restriction (6 cases) of which 62.5% and 33.3% had at least one confounder, respectively. In the disproportionality analyses, a potential safety signal for spontaneous abortion emerged for rivaroxaban (Reporting Odds Ratio, ROR 2.70; 95% CI 1.79-4.07) and apixaban (ROR 6.76; 95% CI 2.99-15.25). However, when the same analyses were performed using only cases without alternative causes, no statistically significant associations for rivaroxaban when compared to all other drugs (ROR 1.05; 95% CI 0.54-2.02) or warfarin (ROR 0.79; 95% CI 0.47-1.32) were found. For apixaban, we found a statistically significant ROR for induced abortion when compared to all other drugs or warfarin. For the majority of cases claiming DOACs-induced teratogenic effects, spontaneous or induced abortion there was at least one alternative cause explaining the occurrence of the adverse events. For rivaroxaban, when cases without confounders were considered, no safety signals emerged. However, for apixaban, we found a potential safety signal suggesting an increased probability of reporting spontaneous/induced abortion rather than other events when compared to all other drugs or warfarin.
The high mortality observed in Covid-19 patients may be related to unrecognized pulmonary embolism, pulmonary thrombosis, or other underlying cardiovascular diseases. Recent data have highlighted ...that the mortality rate of Covid-19 seems to be higher in male patients compared to females. In this paper, we have analyzed possible factors that may underline this sex difference in terms of activity of the immune system and its modulation by sex hormones, coagulation pattern, and preexisting cardiovascular diseases as well as effects deriving from smoking and drinking habits. Future studies are needed to evaluate the effects of sex differences on the prevalence of infections, including Covid-19, its outcome, and the responses to antiviral treatments.
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The results of trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors raised the possibility that this class of drugs provides cardiovascular benefits independently from their ...anti-diabetic effects, although the mechanisms are unknown. Therefore, we tested the effects of SGLT2 inhibitor dapagliflozin on the progression of experimental heart disease in a non-diabetic model of heart failure with preserved ejection fraction. Dahl salt-sensitive rats were fed a high-salt diet to induce hypertension and diastolic dysfunction and were then treated with dapagliflozin for six weeks. Dapagliflozin ameliorated diastolic function as documented by echo-Doppler and heart catheterization, while blood pressure remained markedly elevated. Chronic in vivo treatment with dapagliflozin reduced diastolic Ca2+ and Na+ overload and increased Ca2+ transient amplitude in ventricular cardiomyocytes, although no direct action of dapagliflozin on isolated cardiomyocytes was observed. Dapagliflozin reversed endothelial activation and endothelial nitric oxide synthase deficit, with reduced cardiac inflammation and consequent attenuation of pro-fibrotic signaling. The potential involvement of coronary endothelium was supported by the endothelial upregulation of Na+/H+ exchanger 1in vivo and direct effects on dapagliflozin on the activity of this exchanger in endothelial cells in vitro. In conclusions, several mechanisms may cumulatively play a significant role in the dapagliflozin-associated cardioprotection. Dapagliflozin ameliorates diastolic function and exerts a positive effect on the myocardium, possibly targeting coronary endothelium. The lower degree of endothelial dysfunction, inflammation and fibrosis translate into improved myocardial performance.
We describe a case of acute relapse in a woman with Multiple Sclerosis (MS) shortly after the mRNA COVID-19 vaccination. The patient received a diagnosis of MS in November 2016 at the MS Centre of ...the A. Cardarelli Hospital (South of Italy). Since that moment, her clinical conditions and pharmacological therapies have been managed at this MS centre where, according to national recommendations, in April 2021, the patient received the BNT162b2 vaccine. Almost 48 h after receiving the vaccine, the patient developed paraesthesia and weakness in her left arm and limbs. The neurological examination revealed walking difficulties while the MRI showed three new voluminous enhancing lesions. After having received methylprednisolone iv for 5 days, the patient's neurological symptoms fully recovered. Along with the implementation of COVID-19 vaccination programmes among vulnerable population, further studies are needed in order to improve our knowledge on the benefit/risk ratio of COVID-19 vaccines.
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