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Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging–based SARS-CoV-2 infection assay was developed in VeroE6 African green monkey kidney epithelial cells expressing a stable enhanced green fluorescent protein (VeroE6-eGFP cells) and was used to screen a library of 5676 compounds that passed Phase 1 clinical trials. Eight drugs (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti–SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment.
Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 ± 16.9 to 51.9 ± 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11–1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16–1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05–1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16–1.44/OR = 1.35, 95% CI: 1.23–1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 ± 18.7% pre-restrictions to 81.3 ± 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50–1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18–1.36), and young age (OR = 1.10, 95% CI: 1.03–1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.
The coronavirus has led to a human tragedy, but it need not end up in an economic catastrophe.
In Southern Europe there are signs of a silver lining: the growth rate of the total number of deaths attributed to the coronavirus has been decreasing for weeks in Italy and Spain.
While the effect of the connement measures aim at limiting the spread of the virus is at best uncertain, the economic and social costs of a prolonged lockdown are much less ambiguous and potentially huge. Importantly, these costs can be very unequally distributed.
We argue that it is therefore time to start thinking about how to gradually unlock these countries, and we make some suggestions along this line starting with large-scale testing and continuous re-testing as the most useful pre-condition.
Germany experienced a 6-month second lockdown (November 2020–April 2021) during the COVID-19 pandemic, which included the closure of all physical activity (PA) facilities. The use of online exercise classes (OECs) was promoted by public health and exercise organizations. Using the present cross-sectional online survey, we assess the use of and opinion towards OECs in Germany during the second lockdown. We used contingency tables and the Chi2 test to calculate the frequency of awareness and use of OECs according to PA status, well-being and demographic data, and conducted a binary logistic regression with OEC awareness or use and dichotomized independent predictors. The associations between opinion and activity status, frequency of use, educational attainment, age and body mass index were calculated using Spearman correlations. A total of 993 datasets were analyzed in detail. Of the 785 (79.1%) participants reporting awareness of OECs, 536 tried them, and 262, 188 and 85 used them <1 per week, 1–2 per week and ≥3 per week, respectively. The users were typically active, female participants with poorer mental well-being. The opinions towards OECs varied according to participant characteristics, such as activity status, BMI and age. Overall, regular OEC use was quite limited, and, as such, cannot replace in-person exercise opportunities. Keeping physical activity facilities open and safe must be prioritized in the ongoing pandemic.
The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN2, which was identified in a cell-based antiviral screen. The molecule exerts sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. Time-of-addition studies reveal that Z-Tyr-Ala-CHN2 acts at the early phase of the infection cycle, which is in line with the observation that the molecule inhibits cathepsin L. This results in antiviral activity against SARS-CoV-2 in VeroE6, A549-hACE2, and HeLa-hACE2 cells, but not in Caco-2 cells or primary human nasal epithelial cells since the latter two cell types also permit entry via transmembrane protease serine subtype 2 (TMPRSS2). Given their cell-specific activity, cathepsin L inhibitors still need to prove their value in the clinic; nevertheless, the activity profile of Z-Tyr-Ala-CHN2 makes it an interesting tool compound for studying the biology of coronavirus entry and replication.
The COVID-19 lockdown has significantly disrupted the higher education environment within the Netherlands and led to changes in available study-related resources and study demands of students. These changes in study resources and study demands, the uncertainty and confusion about educational activities, the developing fear and anxiety about the disease, and the implementation of the COVID-19 lockdown measures may have a significant impact on the mental health of students. As such, this study aimed to investigate the trajectory patterns, rate of change, and longitudinal associations between study resources–demands and mental health of 141 university students from the Netherlands before and during the COVID-19 lockdown. The present study employed a longitudinal design and a piecewise latent growth modeling strategy to investigate the changes in study resources and mental health over a 3 month period. The results showed that moderate levels of student resources significantly decreased before, followed by a substantial rate of increase during, lockdown. In contrast, study demands and mental health were reported to be moderate and stable throughout the study. Finally, the growth trajectories of study resources–demands and mental health were only associated before the lockdown procedures were implemented. Despite growing concerns relating to the negative psychological impact of COVID-19 on students, our study shows that the mental health during the initial COVID-19 lockdown remained relatively unchanged.
Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.
Keywords: Severe Acute Respiratory Syndrome; SARS; coronavirus; molecular mechanisms; therapy; vaccination