ABSTRACT
Considerable literature has reported the COVID-19 pandemic's negative mental health sequelae. This surge in mental health problems will likely present to primary care in the coming months. The development of interventions to support GPs in the care of patients with mental health problems is a priority. The aim of this review was to examine interventions which could be implemented in general practice to enhance care of mental health disorders post COVID-19. PubMed, PsycINFO, Cochrane Library, Google Scholar and WHO Global Research on COVID-19 databases were searched following Arksey and O'Malley's scoping review process(1). Initial searches identified 148 articles. Twenty-nine studies were included in the review, mostly randomised control trials, qualitative interviews and surveys. Outcome measures to test feasibility of interventions included the 'Seven-item Generalised Anxiety Disorder Scale' and 'Nine-item Patient Health Questionnaire'. Results were divided into themes: Interventions to improve identification of mental health disorders;Interventions to support GPs;Therapeutic interventions;Telemedicine interventions, and barriers and facilitators to intervention implementation. Interventions requiring active involvement of patients in their own care may be effective. GPs should encourage participation in physical activity andmeditation, implement digitalmental health interventions and incorporate telemedicine into their practice. Our findings suggest a broad range of interventions may be implemented in primary care to tackle the mental health sequelae of COVID-19. Practitioners worldwide must stay informed of relevant research, and actively implement studied interventions to improve the mental health care they offer. Priority areas for future research include biological treatments for mental health sequelae of COVID-19.
ABSTRACT
Background and Aim: Proteases catalyze irreversible post-translational modifications that often alter biological function of the substrate. The protease dipeptidyl peptidase-4 (DPP-4) is a pharmacological target in type 2 diabetes and is abundant in liver. DPP-4 and its sister protease, fibroblast activation protein (FAP), are potential pharmacological targets in steatosis, insulin resistance, cancers, and inflammatory and fibrotic diseases. Recently, DPP-4 has been identified as a potential binding target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein.1,2 A detailed understanding of protein structure, function, and molecular interactions requires a reliable protocol for the large-scale production of highly stable and pure protein. We aimed to optimize production and purification strategies for soluble recombinant human DPP-4 and FAP from Spodoptera frugiperda 9 (Sf9) insect cells. Methods: The Bac-to-Bac Baculovirus Expression System (ThermoFisher) was used. Soluble DPP-4 (residues 29-766) was purified by a four-step procedure: differential ammonium sulfate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in tandem with immobilized metal affinity chromatography, and ion exchange chromatography. Soluble FAP (residues 27-760) was expressed similarly, except for adding a gp67 secretion signal, and then purified similarly. The binding affinities of DPP-4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain were measured using surface plasmon resonance. Results: This optimized DPP-4 purification procedure yielded, on average, 1.36 mg of pure fully active soluble DPP-4 protein per liter of suspension insect cell culture with specific activity 36.4 U/mg. DPP-4 activity greater than 20 U/mg indicates that the enzyme is completely pure. No specific binding between DPP-4 and CoV-2 protein was detected. For FAP, a novel baculovirus expression construct was designed and used to generate abundant active soluble recombinant human FAP expression in Sf9 insect cells for protein purification. Unexpectedly, FAP and DPP-4 behaved differently in hydrophobic interaction chromatography. Nevertheless, soluble FAP was partially purified using a similar purification protocol to DPP-4. Compared with our previous work,3 the DPP-4 now has greater yield and purity, and the FAP has greater yield. Conclusion: A procedure for high-yield DPP-4 that is purified to homogeneity was achieved and used to show that, unlike in Middle East respiratory syndrome (MERS), SARS-CoV-2 does not bind DPP-4. A better understanding of FAP behavior in liquid chromatography was obtained and will be useful for developing an optimized purification strategy.