ABSTRACT
Background/Aims The COVID-19 pandemic has resulted in unprecedented changes to healthcare services. This study aimed to evaluate the impact of the COVID-19 pandemic on referrals to cardiology services in a tertiary hospital. Methods Royal Stoke University Hospital has a cardiac assessment nurse team that provides rapid access to specialist cardiology opinion. All referrals are recorded on a database, which was used to determine how COVID-19 affected the number and types of referrals to cardiology during March–September 2019 and March–September 2020. Results A total of 12 447 referrals were made to the cardiac assessment nurse teams over the evaluation period. Compared to the average number of referrals across all months, there was a decline of 10.5%, 31.2% and 18.5% during March, April and May 2019 respectively. Comparing 2020 to 2019, there were more 999 calls (17.7% vs 15.7%) and accident and emergency referrals (46.5% vs 45.0%), and fewer interhospital referrals (16.0% vs 19.6%). In terms of advice provided for the 999 referrals, a greater number were advised to go to the accident and emergency department (10.5% vs 0%) and direct phone advice provided to those in other settings increased (11.7% vs 0.1%) in 2020. Conclusions The COVID-19 pandemic was associated with a reduction in the number of overall referrals to cardiology, while also demonstrating a shift towards more advice to attend the accident and emergency department for assessment or direct phone advice being provided about management in the community.
ABSTRACT
Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (Ki* = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors.