Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Supraclavicular lymphadenopathy following COVID-19 vaccination: an increasing presentation to the two-week wait neck lump clinic?

The first COVID-19 vaccination was given in December 2020 and there is an effort to vaccinate the international population on a massive scale. Common side effects from the vaccine include headache and tiredness. Regional lymphadenopathy has been described in relation to other vaccines. We describe two cases of supraclavicular reactive lymphadenopathy presenting in patients who had the COVID vaccination in the ipsilateral arm. Awareness of this diagnosis is important for patients presenting to the neck lump clinic.     

Diffuse skin rash in tropical areas: Dengue fever or COVID-19?

There have been several clinical manifestations associated with SARS-CoV-2 infection since 2019, including dermatological signs and symptoms. In this article, the authors report a case of a previously healthy patient with COVID-19 who was mistakenly diagnosed with dengue fever due to a skin rash. By the time the patient's investigation was initiated, Joinville (Santa Catarina, Brazil) had approximately 5,000 confirmed cases of dengue fever and 1,700 cases of COVID-19 in 2020. Thus, the authors emphasize that in endemic regions such as Brazil, the two diseases must be considered until proven otherwise. Finally, the authors warn of the possibility of co-infection with these two viruses in regions that are facing both epidemics at the same time.     

Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

Lipase elevation on admission predicts worse clinical outcomes in patients with COVID-19

Background and objectivesHyperlipasemia is highly prevalent among coronavirus disease 2019 (COVID-19) patients. The aim of this study was to assess the effect of lipase activity, measured at the time of admission, on the clinical course and mortality in COVID-19 patients.MethodsThe population of this study comprised 12,139 patients who were hospitalized due to COVID-19 between June 2020 and June 2021 in a pandemic hospital. Of these, 8819 patients were excluded from the study due to missing data, four patients were excluded due to a diagnosis of acute pancreatitis (according to the revised Atlanta criteria), and 72 patients were excluded due to alcohol use or having a history of chronic pancreatitis. The final study sample consisted of the remaining 3244 COVID-19 patients. Laboratory results, intensive care unit (ICU) follow-up periods, the need for mechanical ventilation, and mortality rates were compared between the normal lipase activity and high lipase activity groups.ResultsThere were 968 (29.8%) patients with high lipase activity at the time of admission. The rate of ICU admission was 36.1% vs. 9.9% (p < 0.001), mechanical ventilation requirement rates were 33.7% vs. 8.3% (p < 0.001), and mortality rates were as 24.6% vs. 6.4% (p < 0.001) in the high lipase activity group compared to the normal lipase activity group. Multivariate regression analysis revealed that high lipase activity was an independent factor in predicting mortality in hospitalized COVID-19 patients (odds ratio [OR]: 3.191, p < 0.001).ConclusionElevated lipase activity without acute pancreatitis at the time of admission in COVID-19 patients was determined as an independent predictor of poor prognosis.     

Vaccines and autoimmunity during the COVID-19 pandemic

To control the pandemic, efficient vaccines must be applied to the population, including patients with autoimmune diseases. Therefore, one can expect that coronavirus disease 2019 (COVID-19) vaccines may influence the underlying autoimmune processes in these patients. Additionally, it is essential to understand whether COVID-19 vaccines would be effective, safe, and provide long-lasting immunological protection and memory. However, the currently available and approved COVID-19 vaccines turned out to be safe, effective, and reliable in patients with autoimmune inflammatory and rheumatic diseases. Furthermore, most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing. In general, the COVID-19 vaccines have been highly tolerated by autoimmune patients. Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.     

Internet of things-based health monitoring system for early detection of cardiovascular events during COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) has currently caused the mortality of millions of people around the world. Aside from the direct mortality from the COVID-19, the indirect effects of the pandemic have also led to an increase in the mortality rate of other non-COVID patients. Evidence indicates that novel COVID-19 pandemic has caused an inflation in acute cardiovascular mortality, which did not relate to COVID-19 infection. It has in fact increased the risk of death in cardiovascular disease (CVD) patients. For this purpose, it is dramatically inevitable to monitor CVD patients’ vital signs and to detect abnormal events before the occurrence of any critical conditions resulted in death. Internet of things (IoT) and health monitoring sensors have improved the medical care systems by enabling latency-sensitive surveillance and computing of large amounts of patients’ data. The major challenge being faced currently in this problem is its limited scalability and late detection of cardiovascular events in IoT-based computing environments. To this end, this paper proposes a novel framework to early detection of cardiovascular events based on a deep learning architecture in IoT environments. Experimental results showed that the proposed method was able to detect cardiovascular events with better performance (95.30% average sensitivity and 95.94% mean prediction values).     

Attitude toward a mandatory COVID-19 vaccination policy and its determinants: Evidence from serial cross-sectional surveys conducted throughout the pandemic in Germany

BackgroundMandating vaccination against COVID-19 is often discussed as a means to counter low vaccine uptake. Beyond the potential legal, ethical, and psychological concerns, a successful implementation also needs to consider citizens’ support for such a policy. Public attitudes toward vaccination mandates and their determinants might differ over time and, hence, should be monitored.MethodsBetween April 2020 and April 2021, we investigated public support for mandatory vaccination policies in Germany and examined individual correlates, such as vaccination intentions, confidence in vaccine safety, and perceived collective responsibility, using a series of cross-sectional, quota-representative surveys (overall N = 27,509).ResultsSupport for a vaccination mandate declined before the approval of the first vaccine against COVID-19 in December 2020 and increased afterwards. However, at the end of April 2021, only half of respondents were in favor of mandatory regulations. In general, mandates were endorsed by those who considered the vaccines to be safe, anticipated practical barriers, and felt responsible for the collective. On the contrary, perceiving vaccination as unnecessary and weighing the benefits and risks of vaccination was related to lower support. Older individuals and males more often endorsed vaccination mandates than did younger participants and females. Interestingly, there was a gap between vaccination intentions and support for mandates, showing that the attitude toward mandatory vaccination was not only determined by vaccination-related factors such as vaccine safety or prosocial considerations.ConclusionsBecause of low public support, mandatory vaccination against COVID-19 should be considered a measure of last resort in Germany. However, if removing barriers to vaccination and educational campaigns about vaccine safety and the societal benefits of high vaccination uptake are not sufficient for increasing vaccination uptake to the required levels, mandates could be introduced. In this case, measures to ensure and increase acceptance and adherence should be taken.