Glucosamine for COVID-19

Objectives To assess the association of habitual glucosamine use with coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large population based cohort. Design Population based, prospective cohort study. Setting UK Biobank. Participants Participants with complete information on habitual glucosamine use and SARS-CoV-2 infection or COVID-19-related outcomes were included. These participants were registered from 2006 to 2010, followed up until 2022 and participated in SARS-CoV-2 tests between 2020 and 2022. Main outcome measures SARS-CoV-2 infection, COVID-19 hospital admission, and COVID-19 mortality. Results At baseline, 20,118 (15.9%) of the 126,518 participants reported as habitual glucosamine users. During the median follow-up 12.16 years, there were 53,682 cases of SARS-CoV-2 infection, 2,120 cases of COVID-19 hospital admission and 548 cases of COVID-19 mortality. The multivariate adjusted hazard ratios of habitual glucosamine users to non-users were 1.02 (95% confidence interval [CI] 0.99 to 1.05) for SARS-CoV-2 infection, 0.73 (95% CI 0.63 to 0.85) for COVID-19 hospital admission, and 0.74 (95% CI 0.56 to 0.98) for COVID-19 mortality. The Cox proportional hazard analysis after propensity-score matching yielded consistent results. Conclusions Habitual glucosamine use seems to be associated with a lower risk of hospital admission and mortality with COVID-19.

Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.