05 November, 2021

Moralizing the COVID-19 Pandemic: Self-Interest Predicts Moral Condemnation of Other’s Compliance, Distancing and Vaccination -

The emergence of the novel coronavirus has put societies under tremendous pressure to instigate massive and rapid behavior change. Throughout history, an effective strategy to facilitate novel behaviors has been to morally condemn those who do not behave in an appropriate way. Accordingly, here, we investigate if complying with the advice of health authorities—e.g. to physically distance or vaccinate—has emerged as a moralized issue during the COVID-19 pandemic. In Study 1, we rely on data (N = 94K) from quota-sampled rolling cross-sectional online surveys from eight countries (Denmark, Sweden, Germany, France, Italy, Hungary, the UK, and the US). We find that large majorities find it justified to condemn those who do not keep a distance to others in public and around half of respondents blame ordinary citizens for the severity of the pandemic. Furthermore, we identify the most important predictors of condemnation to be behavior change and personal concern, while institutional trust and social distrust also play large but less consistent roles. Study 2 offers a registered replication of our findings on a representative sample of Britons (N = 1.5K). It shows that both moralization and condemnation of both vaccination and general compliance are best predicted by self-interested considerations.

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Health behaviors and mental health before and during the COVID-19 pandemic: A longitudinal population-based survey -

Background: Health behaviors such as physical activity and a balanced diet are essential to promote and maintain health. Especially during a crisis, such as the COVID-19 pandemic, they have the potential to buffer against stress and protect mental health. Method: In a longitudinal study with four measurement points over 3 months during the COVID-19 pandemic, about 3,500 randomly selected participants representative of the German population reported their mental health (i.e., anxiety, depression, loneliness), screen time, snack consumption, and physical activity. Results: Symptoms of anxiety, depression, and loneliness were highest during the first month of the pandemic-related lockdown, particularly in women and people in poor health, and decreased over time. Screen time and snacking increased and physical activity decreased compared to pre-lockdown. Snacking and physical activity went back to pre-lockdown levels within 2 months; screen time increased further over time. Snack increase and physical activity decrease was stronger in women than men throughout the lockdown. Generally, more screen time, more snacking, and less physical activity were related to higher symptoms of anxiety, depression, and loneliness across all time points. Changes in health behaviors over time did not predict changes in mental health symptoms. Conclusions: Mental health and health behaviors worsened as an immediate response to stress but mostly returned to pre-crisis levels within 2 to 3 months. Engaging in healthier behaviors is associated with better mental health. This study provides important descriptions of (unintended) side effects of a national crisis and contributes to our understanding of how to preserve mental health.

🖺 Full Text HTML: Health behaviors and mental health before and during the COVID-19 pandemic: A longitudinal population-based survey

Increase of depressive symptoms among adolescents during the first COVID-19 lockdown in Germany - results from a German panel study -

Background The COVID-19 pandemic has fundamentally changed social life within a very short time. Lockdown policies often consider the trade-off between containing the spread of the pandemic and the negative impact for the economy. Policy makers should pay more attention to the psychological and social impacts of the lockdown. Objectives How did the mental health of adolescents in Germany change during the first wave of the COVID-19 pandemic and the lockdown in Germany? Material and Methods Analyses are based on longitudinal data from Germany and a random sample of the birth cohorts 2001-03. Respondents were 15-17 years old at the first interview in 2018/19. 854 adolescents participated in the second wave of the survey in May and June 2020. Depressiveness is assessed with the State-Trait Depression Scale. Results During the first lockdown, adolescents show a significant increase in depressive symptoms. Prior to the lockdown, 10.2 percent had clinically relevant depressive symptoms [CI: 8.0; 12.4]. In spring 2020, the prevalence increased to 25.2 percent [CI: 22.0; 28.4]. Young women have a significantly higher risk of developing depressive symptoms than men of the same age. Immigrant background is an equally strong risk factor. The prevalence of depressive symptoms among adolescents with an immigrant background increased from 11% to 33%. Discussion To address this increased mental health risk and the inequalities, policy makers and society should ensure access and availability of target- group-specific and low-threshold prevention and counselling.

🖺 Full Text HTML: Increase of depressive symptoms among adolescents during the first COVID-19 lockdown in Germany - results from a German panel study

SARS-CoV-2 Aerosol Transmission Indoors: A Closer Look at Viral Load, Infectivity, the Effectiveness of Preventive Measures and a Simple Approach for Practical Recommendations -

Currently, airborne transmission is seen as the most important transmission path for SARS-CoV-2. In this investigation, a classic dose-response model is used on the one hand to find out retrospectively the probable viral load of the infectious source patient at the time of transmission in 25 documented outbreaks. We showed that an infection due to airborne transmission at a distance from the infectious person was probably only possible in the 25 outbreaks examined, with attack rates of 4-100%, if the viral load had been higher than 1E+08 viral copies/ml. This demonstrates that the viral load estimated from the swab might overestimate a person9s infectivity via aerosol, because a person is generally considered infectious, independent of the transmission way, when the viral load from the swab is 1E+06 viral copies/ml. On the other hand, a possible approach is presented to predict the probable situational Attack Rate (PARs) of a group of persons in a room through aerosol particles emitted by an infectious source patient. Four main categories of influence on the risk of infection are formed: First the emitted viruses, depending on the viral load and the amount of respiratory particles, and necessary number of reproducible viruses for infection, second the room-specific data and duration of stay of the group of people, third the activity of the exposed persons, and fourth the effect of personal protection (e.g. wearing masks from infectious and/or susceptible person). Furthermore, a simplified method is presented to calculate either the maximum possible number of persons in a room, so that probably a maximum of one person becomes infected when an infectious person is in the room, or the PARs,simple for a given number of persons, ventilation rate and time of occupancy. We additionally show, taking into account organizational preventive measures, which person-related virus-free supply air flow rates are necessary to keep the number of newly infected persons to less than 1. The simple approach makes it easy to derive preventive organizational and ventilation measures. Our results show that the volume flow rate or a person-related flow rate is a much more effective parameter to evaluate ventilation for infection prevention than the air change rate. We suggest to monitor the CO2 concentration as an easy to implement and valid measurement system for indoor spaces. Finally, we show that of the three measures, besides of wearing masks and increasing ventilation, testing contributes the most to the joint protective effect. This corresponds to the classic approach to implement protection concepts: preventing the source from entering the room and emitting viruses at all. In summary, a layered approach of different measures is recommended to mutually compensate for possible failures of any one measure (e.g. incorrect execution of tests, incorrect fit of masks or irregular window opening), to increase the degree of protection and thus reduce the risk of transmission of SARS-CoV-2.

🖺 Full Text HTML: SARS-CoV-2 Aerosol Transmission Indoors: A Closer Look at Viral Load, Infectivity, the Effectiveness of Preventive Measures and a Simple Approach for Practical Recommendations

Of masks and methylene blue - the use of methylene blue photochemical treatment to decontaminate surgical masks contaminated with a tenacious small non-enveloped norovirus -

Background In the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 uM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure). Methods Here, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate. Results Methylene blue photochemical treatment (100 uM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titres by over four orders of magnitude on surgical mask surfaces. Discussion and Conclusions Inactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness.

🖺 Full Text HTML: Of masks and methylene blue - the use of methylene blue photochemical treatment to decontaminate surgical masks contaminated with a tenacious small non- enveloped norovirus

Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies -

Neutralizing antibodies (nAbs) that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (S-protein) are promising therapeutics for COVID-19. However, natural bivalent nAbs suffer from limited potency and are vulnerable to SARS-CoV-2 variants with mutated RBDs. We report a novel format that enables modular assembly of bi- paratopic, tetravalent nAbs with antigen-binding sites from two distinct nAbs. The diabody-Fc-Fab format consists of a central Fc with a bivalent diabody fused to its N-terminus and two Fabs fused to its C-terminus. The diabody and Fab modules do not interfere with each other, and thus, any diabody can be combined with any Fab in a facile manner. We engineered a diabody-Fc-Fab that contained the paratopes of two distinct nAbs derived from a phage-displayed library of synthetic Abs. The tetravalent nAb was purified in high yields with methods used to produce conventional IgGs, and it exhibited favorable biophysical characteristics comparable to those of approved therapeutic antibodies. The tetravalent nAb bound to the S-protein trimer at least 100-fold more tightly than the bivalent IgGs (apparent KD <1 pM). Most importantly, the tetravalent nAb exhibited extremely high potencies in neutralization assays across a panel of pseudoviruses representing seven natural SARS-CoV-2 variants (IC50 <5 ng/mL), including several that resisted IgGs and are known to evade approved IgG drugs. Taken together, our results showed that the tetravalent diabody-Fc-Fab is a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that far exceed those of conventional bivalent IgGs.

🖺 Full Text HTML: Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies

Safety and immunogenicity of heterologous and homologous inactivated and adenoviral-vectored COVID-19 vaccines in healthy adults -

In light of intermittent supply shortages of individual vaccines and evidence of rare but serious adverse events after vaccination, heterologous regimens for COVID-19 vaccines have gained significant interest. This study aims to assess the reactogenicity and immunogenicity of the heterologous adenoviral vector vaccine regimen (ChAdOx1-S, AstraZeneca; hereafter referred to as AZ) and the inactivated vaccine regimen (CoronaVac; hereafter referred to as CV) regimen in healthy Thai adults immunized between June and September 2021. Our study showed that adverse events following homologous CV-CV and AZ-AZ, and heterologous CV-AZ and AZ-CV combinations, were mild and well tolerated overall. Receptor-binding domain (RBD)-specific antibody responses and neutralizing activities against wild-type and variants of concern after two-dose vaccination were higher in the heterologous CV-AZ and homologous AZ-AZ groups compared to the CV- CV and AZ-CV groups. Conversely, the spike-specific IgA response was detected only in the CV-AZ group after two doses of vaccination. The total interferon gamma response was detected in both the CV-AZ and AZ-CV groups after the two-dose vaccination. Given the shorter completion time of two doses, heterologous CoronaVac followed by ChAdOx1-S can be considered as an alternative regimen to homologous efficacy-proven ChAdOx1-S in countries with circulating variants. Additional studies on the efficacy and durability of immune responses induced by heterologous vaccine regimens are warranted.

🖺 Full Text HTML: Safety and immunogenicity of heterologous and homologous inactivated and adenoviral-vectored COVID-19 vaccines in healthy adults

Estimation of the basic reproduction number of COVID-19 from the incubation period distribution -

Background The estimates of future course of spreading of the SARS-CoV-2 virus are frequently based on Markovian models in which the transitions between the compartments are exponentially distributed. Specifically, the basic reproduction number R0 is also determined from formulae where it is related to the parameters of such models. The observations show that the start of infectivity of an individual appears nearly at the same time as the onset of symptoms, while the distribution of the incubation period is not an exponential. Methods We propose a method for estimation of R0 for COVID-19 based on the empirical incubation period distribution and assumed very short infectivity period that lasts only few days around the onset of symptoms. It is tested on daily new cases in six major countries in Europe, in the first wave of epidemic in spring, 2020. Results The calculations show that even if the infectivity starts two days before the onset of symptoms and stops immediately when they appear, the value of R0 is larger than that from the classical, Markovian approach. For more realistic cases, when only individuals with mild symptoms spread the virus for few days after onset of symptoms, the respective values are even larger. Conclusions The calculations of R0 and other characteristics of spreading of COVID-19 based on the classical, Markovian approaches should be taken very cautiously. Instead, non-Markovian models with general distribution functions of transition between compartments should be considered as more appropriate.

🖺 Full Text HTML: Estimation of the basic reproduction number of COVID-19 from the incubation period distribution

Severity and inpatient mortality of COVID-19 pneumonia from Beta variant infection: a clinical cohort study in Cape Town, South Africa -

Background The SARS-CoV-2 Beta variant, associated with immune escape and higher transmissibility, drove a more severe second COVID-19 wave in South Africa. Individual patient level characteristics and outcomes with the Beta variant are not well characterized. Methods We performed a retrospective cohort study comparing disease severity and inpatient mortality of COVID-19 pneumonia between the first and second wave periods at a referral hospital in Cape Town, South Africa. Beta variant infection was confirmed by genomic sequencing. Outcomes were analyzed with logistic regression and accelerated failure time models. Results 1,182 patients were included: 571 during the first wave period and 611 from the second wave. Beta variant accounted for 97% of infections in the second wave. There was no difference in crude in- hospital mortality between wave periods (first wave 22.2%, second wave 22.1%; p = 0.9). Time to death was decreased with higher weekly hospital admissions (16%; 95% CI, 8 to 24 for every 50-patient increase), age (18%; 95% CI, 12 to 24 for every 10-year increase) and hypertension (31%; 95% CI, 12 to 46). Corticosteroid use delayed time to death by 2-fold (95% CI, 1.5 to 3.0). Admission during the second wave decreased time to death after adjustment for other predictors, but this did not reach statistical significance (24%; 95% CI, 47 to -2). There was no effect of HIV on survival. Conclusions There was a trend towards earlier mortality during the second COVID-19 wave driven by the Beta variant, suggesting a possible biological basis. Use of oral prednisone was strongly protective.

🖺 Full Text HTML: Severity and inpatient mortality of COVID-19 pneumonia from Beta variant infection: a clinical cohort study in Cape Town, South Africa

Coronavirus RNA synthesis takes place within membrane-bound sites -

Infectious bronchitis virus (IBV), a gammacoronavirus, is an economically important virus to the poultry industry as well as a significant welfare issue for chickens. As for all positive strand RNA viruses, IBV infection causes rearrangements of the host cell intracellular membranes to form replication organelles. Replication organelle formation is a highly conserved and vital step in the viral life cycle. Here, we investigate the localization of viral RNA synthesis and the link with replication organelles in host cells. We have shown that sites of viral RNA synthesis and virus-related dsRNA are associated with one another and, significantly, that they are located within a membrane-bound compartment within the cell. We have also shown that some viral RNA produced early in infection remains within these membranes throughout infection. Importantly, we demonstrate conservation across all four coronavirus genera, including SARS-CoV-2. Under-standing more about the replication of these viruses is imperative in order to effectively find ways to control them.

🖺 Full Text HTML: Coronavirus RNA synthesis takes place within membrane-bound sites

Marked enhancement of neutralizing antibody and IFN-γ T-cell responses by GX-19N DNA booster in mice primed with inactivated vaccine -

In response to the COVID-19 pandemic, an unprecedented level of vaccine development has occurred. As a result, various COVID-19 vaccines have been approved for use. Among these, inactivated virus particle vaccines have been widely used worldwide, but additional vaccination strategies are needed because of the short duration of immune responses elicited by these vaccines. Here, we evaluated homologous and heterologous prime-boost regimens using inactivated virus particle vaccine and GX-19N DNA vaccine for their ability to enhance the protective immune response against SARS-CoV-2. We demonstrated that a heterologous prime-boost regimen with the inactivated virus particle vaccine and GX-19N DNA vaccine resulted in enhanced SRBD- and N-specific antibody responses, compared to the homologous inactivated virus particle vaccine prime-boost vaccination. In addition, the neutralizing antibody response was significantly improved with the heterologous inactivated virus particle prime DNA boost regimen, and the neutralizing antibody induced with the heterologous prime boost regimen did not decrease against the SARS-CoV-2 variant of concern. The heterologous inactivated virus particle prime-DNA boost regimen not only significantly increased S- and N-specific IFN-g T cell responses, but also induced an equivalent level of T cell response against SARS-CoV-2 variant of concerns. Our results provide new insights into prophylactic vaccination strategies for COVID-19 vaccination.

🖺 Full Text HTML: Marked enhancement of neutralizing antibody and IFN-γ T-cell responses by GX-19N DNA booster in mice primed with inactivated vaccine

Protein arginylation is regulated during SARS-CoV-2 infection -

In 2019, the world witnessed the onset of an unprecedented pandemic. In September 2021, the infection by SARS-CoV-2 had already been responsible for the death of more than 4 million people worldwide. Recently, we and other groups discovered that SARS-CoV-2 infection induces ER-stress and activation of unfolded protein response (UPR) pathway. The degradation of misfolded/unfolded proteins is an essential element of proteostasis and occurs mainly in lysosomes or proteasomes. The N-terminal arginylation of proteins is characterized as an inducer of ubiquitination and proteasomal degradation by the N-end rule pathway. Here we present, for the first time, data on the role of arginylation during SARS-CoV-2 infection. We studied the modulation of protein arginylation in Vero CCL-81 and Calu-3 cells infected after 2h, 6h, 12h, 24h, and 48h. A reanalysis of in vivo and in vitro public omics data combined with immunoblotting was performed to measure the levels of ATE1 and arginylated proteins. This regulation is seen specifically during infections by coronaviruses. We demonstrate that during SARS-CoV-2 infection there is an increase in the expression of the ATE1 enzyme associated with regulated levels of specific arginylated proteins. On the other hand, infected macrophages showed no ATE1 regulation. An important finding revealed that modulation of the N-end rule pathway differs between different types of infected cells. We also confirmed the potential of tannic acid to reduce viral load, and furthermore, to modulate ATE1 levels during infection. In addition, the arginylation inhibitor merbromin (MER) is also capable of both reducing viral load and reducing ATE1 levels. Taken together, these data show the importance of arginylation during the progression of SARS-CoV-2 infection and open the door for future studies that may unravel the role of ATE1 and its inhibitors in pathogen infection.

🖺 Full Text HTML: Protein arginylation is regulated during SARS-CoV-2 infection

Comparing protein-protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features -

Background: SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 183 million individuals and caused about 4 million deaths globally. A protein-protein interaction network (PPIN) and its analysis can provide insight into the behavior of cells and lead to advance the procedure of drug discovery. The identification of essential proteins is crucial to understand for cellular survival. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common proteins. Analyzing influential proteins and comparing these networks together can be an effective step helping biologists in drug design. Results: We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. PCA- based dimensionality reduction was applied on normalized centrality values. Some measures demonstrated a high level of contribution in comparison to others in both PPINs, like Barycenter, Decay, Diffusion degree, Closeness (Freeman), Closeness (Latora), Lin, Radiality, and Residual. Using validation measures, the appropriate clustering method was chosen for centrality measures. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness. Conclusions: Through analysis and comparison, both networks exhibited remarkable experimental results. The network diameters were equal and in terms of heterogeneity, SARS-CoV-2 PPIN tends to be more heterogeneous. Both networks under study display a typical power-law degree distribution. Dimensionality reduction and unsupervised learning methods were so effective to reveal appropriate centrality measures.

🖺 Full Text HTML: Comparing protein-protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features

Clinically observed deletions in SARS-CoV-2 Nsp1 affect protein stability and its ability to inhibit translation -

Nonstructural protein 1 (Nsp1) is a major pathogenicity factor of SARS-CoV-2. It inhibits host-cell translation, primarily through a direct interaction between its C-terminal domain and the mRNA entry channel of the 40S small ribosomal subunit, with an N-terminal {beta}-barrel domain fine-tuning the inhibition and promoting selective translation of viral mRNA. SARS-CoV-2 nsp1 is a target of recurring deletions, some of which are associated with altered COVID-19 disease progression. To provide the biochemical basis for this, it is essential to characterize the efficiency of translational inhibition by the said protein variants. Here, we use an in vitro translation system to investigate the translation inhibition capacity of a series of clinically observed Nsp1 deletion variants. We find that a frequently observed deletion of residues 79-89 destabilized the N-terminal domain (NTD) and severely reduced the capacity of Nsp1 to inhibit translation. Interestingly, shorter deletions in the same region have been reported to effect the type I interferon response but did not affect translation inhibition, indicating a possible translation-independent role of the Nsp1 NTD in interferon response modulation. Taken together, our data provide a mechanistic basis for understanding how deletions in Nsp1 influence SARS-CoV-2 induction of interferon response and COVID-19 progression.

🖺 Full Text HTML: Clinically observed deletions in SARS-CoV-2 Nsp1 affect protein stability and its ability to inhibit translation

Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution -

Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii).

🖺 Full Text HTML: Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

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