Understanding the clinical utility of favipiravir (T-705) in coronavirus disease of 2019: a review.

The coronavirus disease of 2019 (COVID-19) has caused significant morbidity and mortality among infected individuals across the world. High transmissibility rate of the causative virus - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - has led to immense strain and bottlenecking of the health care system. While noteworthy advances in vaccine development have been made amid the current global pandemic, most therapeutic agents are repurposed from use in other viral infections and are being evaluated for efficacy in COVID-19. Favipiravir, an orally administered drug originally developed in Japan against emerging influenza viral strains, has been shown to have widespread application and safety across multiple ribonucleic acid (RNA) viral infections. With a strong affinity toward the viral RNA-dependent RNA polymerase (RdRp), favipiravir could be a promising therapy against SARS-CoV-2, by targeting downstream viral RNA replication. Initial trials for usage in COVID-19 have suggested that favipiravir administration during initial infection stages, in individuals with mild to moderate infection, has a strong potential to improve clinical outcomes. However, additional well-designed clinical trials are required to closely examine ideal timing of drug administration, dosage, and duration, to assess the role of favipiravir in COVID-19 therapy. This review provides evidence-based insights and throws light on the current clinical trials examining the efficacy of favipiravir in tackling COVID-19, including its mechanism, pharmacodynamics, and pharmacokinetics.

Clinical decision support tool and rapid point-of-care platform for determining disease severity in patients with COVID-19.

SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

Clinical Decision Support Tool and Rapid Point-of-Care Platform for Determining Disease Severity in Patients with COVID-19.

SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

In vivo efficacy of calcium phosphate-based synthetic-bone-mineral on bone loss resulting from estrogen and mineral deficiencies.

Osteopenia and osteoporosis affect over 40 million US adults 50 years and older. Both diseases are strongly influenced by estrogen and nutritional-mineral deficiencies. This study investigates the efficacy of orally delivered synthetic-bone-mineral (SBM), a newly developed calcium phosphate based biomaterial, on reversing bone loss induced by these two critical deficiencies. Thirty 3-month-old female rats were randomly allocated to either control-sham surgery on normal diet; or one of the four experimental groups: Sham surgery on a low mineral diet (LMD), ovariectomized (OVX) on LMD, OVX on LMD with SBM with/without fluoride (F). The rats were sacrificed after 6 months, at 9-month-old. After 6 months, although all groups lost bone mineral density relative to controls, the supplemented OVX rats showed higher bone mineral density than their unsupplemented counterparts. The 2 SBM supplemented groups improved bone loading capacity by 28.1 and 35.4% compared to the OVX LMD group. Bones from supplemented rats exhibited higher inorganic/organic ratios. The addition of F did not have a significant influence on bone loss. Our findings suggest that SBM supplement is effective in maintaining bone health and offsetting the deleterious effects of estrogen and/or mineral deficiencies on bone density, microarchitecture, and strength.

Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats.

Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-computed tomography (µCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1622-1632, 2016.