On 11 March 2020, the World Health Organization (WHO) classified the Coronavirus Disease 2019 (COVID-19) as a global pandemic, which tested healthcare systems, administrations, and treatment ingenuity across the world. COVID-19 is caused by the novel beta coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the inception of the pandemic, treatment options have been either limited or ineffective. Remdesivir, a drug originally designed to be used for Ebola virus, has antiviral activity against SARS-CoV-2 and has been included in the COVID-19 treatment regimens. Remdesivir is an adenosine nucleotide analog prodrug that is metabolically activated to a nucleoside triphosphate metabolite (GS-443902). The active nucleoside triphosphate metabolite is incorporated into the SARS-CoV-2 RNA viral chains, preventing its replication. The lack of reported drug development and characterization studies with remdesivir in public domain has created a void where information on the absorption, distribution, metabolism, elimination (ADME) properties, pharmacokinetics (PK), or drug-drug interaction (DDI) is limited. By understanding these properties, clinicians can prevent subtherapeutic and supratherapeutic levels of remdesivir and thus avoid further complications in COVID-19 patients. Remdesivir is metabolized by both cytochrome P450 (CYP) and non-CYP enzymes such as carboxylesterases. In this narrative review, we have evaluated the currently available ADME, PK, and DDI information about remdesivir and have discussed the potential of DDIs between remdesivir and different COVID-19 drug regimens and agents used for comorbidities. Considering the nascent status of remdesivir in the therapeutic domain, extensive future work is needed to formulate safer COVID-19 treatment guidelines involving this medication.

Objective The relationship between 25-hydroxyvitamin D3 (25(OH)D), the surrogate marker for vitamin D 3 , serum concentration and COVID-19 has come to the forefront as a potential pathway to improve COVID-19 outcomes. The current evidence remains unclear on the impact of vitamin D status on the severity and outcomes of COVID-19 infection. To explore possible association between low 25(OH)D levels and risk of developing severe COVID-19 (i.e. need for invasive mechanical ventilation, the length of hospital stay, total deaths). We also aimed to understand the relationship between vitamin D insufficiency and elevated inflammatory and cardiac biomarkers. Methods We conducted a comprehensive electronic literature search for any original research study published up to March 30, 2021. For the purpose of this review, low vitamin D status was defined as a range of serum total 25(OH)D levels of <10 to <30 ng/ml. Two independent investigators assessed study eligibility, synthesized evidence, analyzed, critically examined, and interpreted herein. Results Twenty-four observational studies containing 3637 participants were included in the meta-analysis. The mean age of the patients was 61.1 years old; 56% were male. Low vitamin D status was statistically associated with higher risk of death (RR, 1.60 (95% CI, 1.10–2.32), higher risk of developing severe COVID-19 pneumonia (RR: 1.50; 95% CI, 1.10–2.05). COVID-19 patients with low vitamin D levels had a greater prevalence of hypertension and cardiovascular diseases, abnormally high serum troponin and peak D-dimer levels, as well as elevated interleukin-6 and C-reactive protein than those with serum 25(OH)D levels ≥30 ng/ml. Conclusions In this meta-analysis, we found a potential increased risk of developing severe COVID-19 infection among patients with low vitamin D levels. There are plausible biological mechanisms supporting the role of vitamin D in COVID-19 severity. Randomized controlled trials are needed to test for potential beneficial effects of vitamin D in COVID-19 outcomes.

Ionic liquids are salts in which the ions are poorly coordinated, which causes them to exist in liquid form below 100°C, or at room temperature. Therefore, these are also defined as room temperature ionic liquids (RTILs). In ionic liquids, at least one ion has a delocalized charge and one component is organic, which prevents the formation of a stable solid form of crystal lattice. Physical properties of ionic liquids, such as melting point, viscosity, and solubility of starting materials and other solvents, are impacted by the substituents on the organic component and by the counterions. Many ionic liquids have even been developed to address specific synthetic problems and that is the reason these are also termed as "designer solvents". Ionic liquids are considered as “green solvents” that exhibit several unique characteristics such as high ionic conductivity, high solvation power, thermal stability, low volatility, and recyclability. Although very useful with several advantages, ionic liquids have some limitations that include high cost and ease of recycling. Moreover, the toxicity and biodegradability of ionic liquids are not yet well understood. Nonetheless, ionic liquids can potentially be used in the field of pharmacy in drug design and formulation development. In drug or vaccine dosage formulation development, ionic liquids can be used as a solubility enhancer, permeability enhancer, stabilizer, targeted delivery inducer, stealth property provider or bioavailability enhancer. In this article we reviewed the physical properties of ionic liquids and potential application of ionic liquids in developing formulations for vaccines and small molecule drugs (A table has been added).

Purpose: Vitamin D has immunomodulatory properties that can be useful in COVID-19 patients. We performed a meta-analysis of observational studies to analyze the association of vitamin D levels with the inflammatory markers in COVID-19 patients. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and ClinicalTrial.gov for any relevant studies with comparison data reporting vitamin D levels and inflammatory markers in COVID-19 patients. A literature search was conducted from December 1, 2019, to January 14, 2022. Vitamin D deficiency was defined by each individual study and ranged from <9.9 ng/mL to <30 ng/mL. The inflammatory markers of interest were interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, procalcitonin, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), fibrinogen and D-dimer. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Two independent investigators assessed study eligibility and synthesized the evidence. Results: Thirty-two observational studies were included comprising of 7,771 patients ranging from 40-81 years of age with 57.1% being male. Meta-analysis showed that patients that were vitamin D sufficient (levels >30ng/mL) had statistically significant lower levels of IL-6, CRP, ferritin, LDH, fibrinogen, and D-dimer compared to vitamin D deficient group. With the highest mean difference found in ferritin (95.62; 95% CI, 33.14-158.10); P=0.003; I2=99%). No significant reductions were found in ESR (P=0.97). All inflammatory markers analyzed were higher than the normal healthy reference ranges in both groups. Conclusions: Our results suggest that low vitamin D levels are associated with increased inflammatory marker levels. Vitamin D deficiency may potentially serve as an early identifier for COVID-19 patients at high risk of developing severe inflammatory conditions as well as thrombotic complications. Randomized controlled trials should be conducted to establish a causal relationship.

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