ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2 (preprint)

Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism may associate with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and spike protein and between ApoE and also the SARS-CoV-2 primary receptor ACE2. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.Results ApoE gene polymorphism (ε4 carries genotypes VS non-ε4 carries genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI: 1.18–1.76) and progression (P < 0.00001, OR = 1.85, 95% CI: 1.50–2.28) of COVID-19. ApoE interacts with both the spike protein and ACE2 but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1–7.Conclusions ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin–angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

Constructing a Decision Model for Health Club Members to Purchase Coaching Programs during the COVID-19 Epidemic

The recent COVID-19 epidemic has affected the global sports industry to a certain extent, and health clubs are no exception. To avoid unsustainable operations, health clubs need to restructure their programs to suit members' needs. Therefore, this study constructs a two-stage framework model to evaluate health club members' purchase of coaching programs. The first stage is to construct a hierarchy of evaluation, using the modified Delphi method, to select suitable criteria and extended sub-criteria, and add and delete them through expert discussion. In the second stage, we use the pairwise comparison matrix to calculate the weight of each criterion and sub-criterion to influence each other. Next, we evaluate and compare physical, online and offline, and live-stream coaching programs, by using network hierarchy analysis to identify the best class purchase plan during the epidemic and provide relevant suggestions. The results of the study found that during the epidemic, the primary sales were for weight training among physical programs (0.314), and activity classes among online and offline programs (0.633) as well as live-stream coaching programs (0.280). These findings have implications for health clubs in deciding which mode they need to adopt for sustainable operations.

ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2 (preprint)

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease.

One-Year Recording of Cardiac Arrhythmias in a Non-Infected Population with Cardiac Implantable Devices During the COVID-19 Pandemic.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) was associated with a higher risk of arrhythmia in infected patients. However, there are no reports about the effect of the ongoing pandemic on arrhythmias in the non-infected population. We measured the arrhythmia burden in a non-infected population with cardiac implantable devices. METHODS: The arrhythmia burden during the COVID-19 pandemic was compared to a 6-month interval in the pre-COVID-19 period. The COVID-19 pandemic was divided into high-risk (17 January 2020 to 16 March 2020) and low-risk periods (17 March 2020 to 17 July 2020) according to whether there were locally infected patients. Arrhythmia burdens were compared among the pre-COVID-19, high-risk, and low-risk periods. RESULTS: A total of 219 patients with 1859 episodes were included. We observed a larger proportion of patients with atrial fibrillation (AF) during the COVID-19 pandemic (38.36% vs 26.03%, p = 0.006). There was not significantly more ventricular arrhythmia during the COVID period than the pre-COVID-19 period (p > 0.05). During the high-risk period, daily frequency of non-sustained ventricular tachycardia (NSVT) (0.0172, 0.0475 vs 0.0109, 0.0164, p < 0.05), atrial tachycardia (AT) (0.0345, 0.0518 vs 0.0164, 0.0219 p < 0.05) and AF (0.0345, 0.0432 vs 0.0164, 0.0186, p < 0.05) and daily duration of NSVT (0.1982, 0.2845 vs 0.0538, 0.1640 p < 0.05) were higher and longer than those in the pre-COVID-19 period. Regression modeling showed that the impact of COVID-19 pandemic lead to an increased onset of AF (odds ratio 2.465; p < 0.01). Patients with paroxysmal AF who had undergone a previous radiofrequency ablation had a lower burden of AF (incidence 21.43% vs 55.00%, P = 0.049, daily frequency 0.0000, 0.0027 vs 0.0000, 241.7978, P = 0.020) during the pandemic. CONCLUSION: The COVID-19 pandemic contributed to a higher burden of arrhythmias in non-infected patients. Patients would experience a lower burden of AF following radiofrequency ablation treatment, and this effect persisted during the pandemic.

Re-Thinking the Role of Government Information Intervention in the COVID-19 Pandemic: An Agent-Based Modeling Analysis

The COVID-19 pandemic imposes new challenges on the capability of governments in intervening with the information dissemination and reducing the risk of infection outbreak. To reveal the complexity behind government intervention decision, we build a bi-layer network diffusion model for the information-disease dynamics that were intervened in and conduct a full space simulation to illustrate the trade-off faced by governments between information disclosing and blocking. The simulation results show that governments prioritize the accuracy of disclosed information over the disclosing speed when there is a high-level medical recognition of the virus and a high public health awareness, while, for the opposite situation, more strict information blocking is preferred. Furthermore, an unaccountable government tends to delay disclosing, a risk-averse government prefers a total blocking, and a low government credibility will discount the effect of information disclosing and aggravate the situation. These findings suggest that information intervention is indispensable for containing the outbreak of infectious disease, but its effectiveness depends on a complicated way on both external social/epidemic factors and the governments’internal preferences and governance capability, for which more thorough investigations are needed in the future.