Changes in dispensing of anti-osteoporotic drugs during COVID-19 pandemic

Care of osteoporosis patients during COVID-19 pandemic is challenging. Due to lockdowns and restrictions, the management of osteoporosis has changed. Diagnosis of osteoporosis decreased and the influence of COVID-19 on drug prescriptions and dispensing is currently unclear. Therefore, the aim of the study was to assess the dispensing of anti-osteoporotic drugs during the Covid19 pandemic. Methods This study was a nationwide retrospective register-based observational study which included all patients in Austria aged >= 50 who received at least one prescription for anti-osteoporotic drug between January 2016 and November 2020. Pseudonymized individual-level patients' data were obtained from social insurance authorities and the Federal Ministry of Labour, Social Affairs, Health and Consumer Protection in Austria. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) Denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) for the prediction of drug dispensing. Results There were 2,884,627 dispensing of anti-osteoporotic drugs by 318,573 patients between 2016-2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during COVID-19 pandemic, compared to the non-COVID-19 period. The dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased during COVID- 19. The prescriptions for DMAB decreased during the first lock-down in March and April 2020 (24 %), however increased by 29.1 % for the total observation time. The ARIMA model for alendronate showed, that the estimated step change was minus 1443 dispensing (95 % CI - 2870 to - 17), while the estimated change in slope was minus 29 dispensing per month (95 % CI - 327 to 270). Thus, there were 1472 (1443 + 29) fewer dispensing in March 2020 than predicted had the lockdown not occurred. Discussion The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during the first COVID-19 lockdown. The largest drops in absolute terms were observed for ibandronate, followed by alendronate, denosumab, zolendronic acid and risendronate. The observed decrease of DMAB during the first lockdown, was compensated in the following months. Current evidence suggests no need for discontinuation of anti-osteoporotic drugs during COVID-19 pandemic, nor because of vaccination. Taking into account the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even in times of pandemics.

Neutralization of Middle East Respiratory Syndrome coronavirus through a scalable nanoparticle vaccine

MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily upscalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV Spike protein into cucumber- mosaic virus-like particles. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine (mCuMVTT-MERS) consists of unmodified wild type monomers and genetically modified monomers displaying RBM, both co-assemble in a prokaryotic expression system. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the expression process in E. coli. The ability of the engineered vaccine to bind to MERS-CoV receptor DPP4 was tested in a competitive ELISA. To test the safety and immunogenicity of mCuMVTT-MERS Balb/cOlaHsd mice were primed with 100ug VLPs and boosted on day 28. The developed vaccine induced high anti-RBD and anti-Spike antibodies in a murine model, showing high binding avidity and the ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate in dromedaries and humans.

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV_TT). The RBD displayed CuMV_TT bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMV_TT resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.

COVID-19 Vaccine Acceptance and Hesitancy in Low and Middle Income Countries, and Implications for Messaging (preprint)

BackgroundAs vaccination campaigns are deployed worldwide, addressing vaccine hesitancy is of critical importance to ensure sufficient immunization coverage. We analyzed COVID-19 vaccine acceptance across 15 samples covering ten low- and middle-income countries (LMICs) in Asia, Africa, and South America, and two higher income countries (Russia and the United States). MethodsStandardized survey responses were collected from 45,928 individuals between June 2020 and January 2021. We estimate vaccine acceptance with robust standard errors clustered at the study level. We analyze stated reasons for vaccine acceptance and hesitancy, and the most trusted sources for advice on vaccination, and we disaggregate acceptance rates by gender, age, and education level. FindingsWe document willingness to take a COVID-19 vaccine across LMIC samples, ranging from 67% (Burkina Faso) to 97% (Nepal). Willingness was considerably higher in LMICs (80%) than in the United States (65%) and Russia (30%). Vaccine acceptance was primarily explained by an interest in personal protection against the disease (91%). Concern about side effects (40%) was the most common reason for reluctance. Health workers were considered the most trusted sources of information about COVID-19 vaccines. InterpretationGiven high levels of stated willingness to accept a COVID-19 vaccine across LMIC samples, our study suggests that prioritizing efficient and equitable vaccine distribution to LMICs will yield high returns in promoting immunization on a global scale. Messaging and other community-level interventions in these contexts should be designed to help translate intentions into uptake, and emphasize safety and efficacy. Trusted health workers are ideally positioned to deliver these messages. FundingBeyond Conflict, Bill and Melinda Gates Foundation, Columbia University, Givewell.org, Ghent University, HSE University Basic Research Program, International Growth Centre, Jameel Poverty Action Lab Crime and Violence Initiative, London School of Economics and Political Science, Mulago Foundation, NOVAFRICA at the Nova School of Business and Economics, NYU Abu Dhabi, Oxford Policy Management, Social Science Research Council, Trinity College Dublin COVID19 Response Funding, UK Aid, UKRI GCRF/Newton Fund, United Nations Office for Project Services, Weiss Family Fund, WZB Berlin Social Science Center, Yale Institute for Global Health, Yale Macmillan Center, and anonymous donors to IPA and Y-RISE