05 October, 2021

Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion -

Background: B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution. Methods: Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patients original presentation and 10 months later. Results: Over the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples reflecting the heterogeneity of the initial infection were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection. Conclusions: The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants.

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CAN DISASTERS IMPROVE THE TOURISM INDUSTRY? The role of normative, cognitive and relational expectations in shaping industry response to disaster-induced disruption -

COVID-19 led to the hibernation of tourism activities globally, causing substantial economic loss and putting at risk the survival of many tourism businesses. At the same time, the reduction in travel activity led to an immediate and unprecedented reduction of global carbon emissions. Many academics argue that the tourism industry should be rebuilt in a more sustainable way post-COVID-19. Based on the sociological theory on response to disruption, the present study provides initial empirical evidence that long-lasting environmental benefits are unlikely to result from the pandemic. Recovery guidelines issued by the UNWTO and six member-based industry associations from different geographical locations and representing different types of tourism businesses form the basis of the empirical analysis. Member-based industry associations represent key information brokers during the pandemic; they convey information and advice to their member businesses. The result of the content analysis indicates the dominant impact of normative expectations, which exclusively focus on re-establishing the pre-COVID-19 status. While there is little indication that cognitive expectations – which view the pandemic as an opportunity to transform business operations to be more environmentally sustainable – will be leveraged. This stands in stark contrast to the collective hope that the tourism industry will become more sustainable after the pandemic.

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IMPLEMENTATION OF FATWA ULAMA COUNCIL ACEH CONCERNING MAINTAINING FARDHU KIFAYAH FOR THE MUSLIM’S CORPSE INFECTED BY COVID 19 IN BANDA ACEH 2021 -

Abstract: The phenomenon of the people who forcibly took covid’s corpse 19 from the hospital to be taken care of by Fardhu Kifayah by his family and the community, became a conclusion that there was community doubt about the management of Tajhiz Mayat conducted by the hospital. Coupled with the circulation of the video of the Ruku movement ’in the corpse prayer conducted by unscrupulous parties at the Hospital, became added doubts from the public against the hospital. To solve this problem, this research uses a Descriptive Analysis approach, namely by formulating a question, namely How to arrange Covid 19’s body in Banda Aceh and this question will be answered with several theories and data sets from the field. So it was concluded in a conclusion that answered the formulation of the problems mentioned. Theoretically the spread of covid 19 is very fast, the size of the virus is only 0.1 micrometer and is in body fluids, especially nasopharyngeal fluid and oropharyngeal fluids of infected people, fluids in the body of covid 19 bodies can get out through every gap of the body such as mouth, nose, eye and rectum, because it requires special techniques in its management. Fardhu kifayah to covid 19 bodies should be carried out by trained Ustad and trained health workers, so that the spread stopped. The results of this study concluded that the management of the Moslem bodies died at Zainal Abidin Hospital in Banda Aceh was in accordance with the Fatwa of the Aceh Ulama Council (MPU) and the bodies were handled by trained Ustad and health workers.

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Why a Globally Fair COVID-19 Vaccination? An Analysis based on Agent-Based Simulation -

In this paper, an Agent-Based Model (ABM) is proposed to evaluate the impact of COVID-19 vaccination drive in different settings. The main focus is to evaluate the counter-effectiveness of disparity in vaccination drive among different regions/countries. The model proposed is simple yet novel in the sense that it captures the spatial transmission-induced activity into consideration, through which we are able to relate the transmission model to the mutated variations of the virus. Some important what-if questions are asked in terms of the number of deaths, and time required and the percentage of the population needed to be vaccinated before the pandemic is eradicated. The simulation results have revealed that it is necessary to maintain a global (rather than regional or country-oriented) vaccination drive in case of a new pandemic or continual efforts against COVID-19.

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Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2 -

SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina. Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p<0.0001). The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p=0.005). A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS- CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p=0.008). Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p<0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naive subjects by two doses of the vaccine (p<0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects. Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels. Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

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COVID-19 Vaccine: Newspaper Coverage of the side effects of the vaccine in Nigeria -

Abstract Background: COVID-19 Vaccine hesitancy is increasing globally, and this threatens the world ability to bring the pandemic under control. The way the media reports on the vaccine may influence or affect how the population perceive the safety and efficacy of the vaccine. Methods: The aim of this study was to determine how newspapers in Nigeria report stories about the vaccine and the side effects of the vaccine amidst the growing fear on the safety of the vaccine. A total of 4 national daily newspapers were randomly selected for the study. These are Leadership, Guardian, Nation and Punch newspapers. The study was anchored on agenda setting theory. Quantitative content analysis research was used for the study. The duration of the study was the day the vaccine was introduced in Nigeria: March 1st,2021 to July 31st, 2021. An Excel sheet served as the instrument for data collection and analysis done using SPSS version 25 with the level of significance predetermined at a p-value less than 0.05. Results: Key findings from this research were: Government officials and technical experts were predominantly used by the newspapers as the source of their information. There was a mixed reporting of vaccine side effects with a significant difference between those newspaper publications that reported vaccine side effects and those that did not. Amongst those that reported side effects, there was also a significant difference between those that communicated how and where to report the side effects as against those that did not. Conclusion: As part of the effort to curtail vaccine hesitancy, a continuous improvement in communicating the vaccine efficacy and safety is needed. Keywords: coverage; side-effects; newspaper, COVID-19; vaccine Nigeria;

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Determination of utility of 3 minute and 6 minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary hospital in North India -

Introduction: There have been 214 million confirmed cases of COVID-19 worldwide with a total death tally of 4.4 million. The current study aims to determine the predictive value of 3 minute and 6-minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary care hospital in North India. Methods: The study population consisted of adults (age more than 18 years) with a confirmed diagnosis of Covid-19 by RT-PCR on nasopharyngeal specimens. Patients with only mild illness were enrolled. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, vital signs and laboratory parameters were recorded. The 3 and 6 minute walk test was performed daily from admission till discharge or progression of severity of COVID-19 and it was used to calculate BDS and NEWS2 scores. Results: Our study consisted of 50 patients with 34 (68%) males and the mean (SD) age of the patient population being 28.1 (6.4) years. The most common symptoms were fever, sore throat, and cough. All laboratory parameters were within normal ranges for all the patients. 96% recovered without progression, while only 4% of them progressed to moderate illness. Results of the 3 and 6 minutes walk tests, BDS and NEWS2 scores showed improvement over the course of hospital stay. Conclusions: Although the walk tests and the scores improved over time, they failed to predict the disease progression.

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Unique Peptide Signatures Of SARS-CoV-2 Against Human Proteome Reveal Variants’ Immune Escape And Infectiveness -

SARS-CoV-2 pandemic has emerged the necessity of the identification of sequences sites in viral proteome appropriate as antigenic sites and treatment targets. In the present study, we apply a novel approach for deciphering the virus-host organism interaction, by analyzing the Unique Peptides of the virus with a minimum amino acid sequence length defined as Core Unique Peptides (CrUPs) not of the virus per se, but against the entire proteome of the host organism. The result of this approach is the identification of the CrUPs of the virus itself, which do not appear in the host organism proteome. Thereby, we analyzed the SARS-CoV-2 proteome for identification of CrUPs against the Human Proteome and they are defined as C/H-CrUPs. We found that SARS-CoV-2 include 7.503 C/H-CrUPs, with the SPIKE_SARS2 being the protein with the highest density of C/H-CrUPs. Extensive analysis indicated that the P681R mutation produces new C/H-CrUPs around the R685 cleavage site, while the L452R mutation induces the loss of antigenicity of the NF9 peptide and the strong(er) binding of the virus to ACE2 receptor protein. The simultaneous existence of these mutations in variants like Delta results in the immune escape of the virus, its massive entrance into the host cell, a notable increase in virus formation, and its massive release and thus elevated infectivity.

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Towards the global equilibrium of COVID-19: statistical analysis of country-level data -

Objectives: In our study, we explore the COVID-19 dynamics to test whether the virus has reached its equilibrium point and to identify the main factors explaining R and CFR variability across countries. Design: A retrospective study of publicly available country-level data. Setting: Fifty countries having the highest number of confirmed COVID–19 cases at the end of September 2021. Participants: Aggregated data including 213 976 306 COVID-19 cases confirmed in the selected fifty countries from the start of the epidemic to September 30, 2021. Primary and secondary outcome measures: The daily values of COVID-19 R and CFR measures were estimated using country-level data from the Our World in Data website. Results: The mean values of country–level moving averages of R and CFR went down from 1.118 and 6.3%, respectively, on June 30, 2020 to 1.083 and 3.6% on September 30, 2020 and to 1.015 and 1.8% by September 30, 2021. In parallel, the 10% to 90% inter-percentile range of R and CFR moving averages decreased from 0.288 and 13.3%, respectively, on June 30, 2020, to 0.151 and 7.7% on September 30, 2020, and to 0.107 and 3.3% by September 30, 2021. According to a comparison of the country–level 180–day moving averages of R and CFR calculated on September 30, 2021, an increase of 1% in the Delta variant share is associated with an increase of 0.0009 (95% CI 0.000 to 0.002) in the average Reproduction Number R, while an increase of 1% in the total percentage of confirmed COVID-19 cases per country9s population is associated with a decrease of 0.005 (95% CI 0.000 to 0.010) in the average R. Also, an increase of 1% in the total percentage of fully vaccinated people per country9s population is associated with a decrease of 0.04% (95% CI 0.01% to 0.06%) in the average CFR. Other virological, demographic, economic, immunization, or stringency factors were not statistically significantly associated with either R or CFR across the explored countries. Conclusions: The slow decrease in the country-level moving averages of R, approaching the level of 1.0 and accompanied by repeated outbreaks (“waves”) in various countries, may indicate that COVID-19 has reached its point of a stable endemic equilibrium. A regression analysis implies that only a prohibitively high level of herd immunity (about 63%) may stop the endemic by reaching a stable disease-free equilibrium. It also appears that fully vaccinating about 70% of a country9s population should be sufficient for bringing the CFR close to the level of a seasonal flu (about 0.1%). Thus, while the currently available vaccines prove to be effective in reducing the mortality from the existing COVID-19 variants, they are unlikely to stop the spread of the virus in the foreseeable future. It is noteworthy that no statistically significant effects of government measures restricting the people9s behavior (such as lockdowns) were found in the analyzed data.

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In Vitro Activity of Cysteamine Against SARS-CoV-2 Variants Alpha, Beta, Gamma and Delta -

Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we demonstrate broad antiviral activity of cysteamine HCl in vitro against variants of SARS- CoV-2 assayed in a highly permissible Vero cell line. Cysteamine HCl inhibited infection of alpha, beta, gamma and delta variants effectively and the inhibitory activity was shown to manifest during the early stages of viral infection. Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 3 to 4 times higher than that required to inhibit SARS CoV-2 in tissue culture. Application of cysteamine as a topical nasal treatment can potentially : 1) mitigate existing infection 2) prevent infection in exposed individuals, and 3) limit the contagion in vulnerable populations.

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Structure selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern -

Successful control of the COVID-19 pandemic depends on vaccines that prevent transmission. The full-length Spike protein is highly immunogenic but the majority of antibodies do not target the virus: ACE2 interface. In an effort to concentrate the antibody response to the receptor-binding motif (RBM) we generated a series of conformationally- constrained immunogens by inserting solvent-exposed RBM amino acid residues into hypervariable loops of an immunoglobulin molecule. Priming C57BL/6 mice with plasmid (p)DNA encoding these constructs yielded a rapid memory response to booster immunization with recombinant Spike protein. Immune sera antibodies bound strongly to the purified receptor-binding domain (RBD) and Spike proteins. pDNA primed for a consistent response with antibodies efficient at neutralizing authentic WA1 virus and two variants of concern (VOC), B.1.351 and B.1.617.2. These findings demonstrate that immunogens built on structure selection can focus the response to conserved sites of vulnerability shared between wildtype virus and VOCs and induce neutralizing antibodies across variants.

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Hierarchical Gaussian Processes and Mixtures of Experts to Model COVID-19 Patient Trajectories -

Gaussian processes (GPs) are a versatile nonparametric model for nonlinear regression and have been widely used to study spatiotemporal phenomena. However, standard GPs offer limited interpretability and generalizability for datasets with naturally occurring hierarchies. With large-scale, rapidly-updating electronic health record (EHR) data, we want to study patient trajectories across diverse patient cohorts while preserving patient subgroup structure. In this work, we partition our cohort of over 2000 COVID-19 patients by sex and ethnicity. We develop and apply a hierarchical Gaussian process and a mixture of experts (MOE) hierarchical GP model to fit patient trajectories on clinical markers of disease progression. A case study for albumin, an effective predictor of COVID-19 patient outcomes, highlights the predictive performance of these models. These hierarchical spatiotemporal models of EHR data bring us a step closer toward our goal of building flexible approaches to capture patient data that can be used in real-time systems.

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Dynamic Allostery Highlights the Evolutionary Differences between the CoV-1 and CoV-2 Main Proteases -

The SARS-CoV-2 coronavirus has become one of the most immediate and widely-studied systems since its identification and subsequent global outbreak from 2019-2020. In an effort to understand the biophysical changes as a result of mutations, the mechanics of multiple different proteins within the SARS-CoV-2 virus have been studied and compared with SARS-CoV-1. Focusing on the main protease (mPro), we first explored the long range dynamic-relationship, particularly in cross-chain dynamics, using the Dynamic Coupling Index (DCI) to investigate the dynamic coupling between the catalytic site residues and the rest of the protein, both inter and intra chain for the CoV-1 and CoV-2 mPro. We found that there is significant cross-chain coupling between these active sites and distal residues in the CoV-2 mPro but it was missing in CoV-1. The enhanced long distance interactions, particularly between the two chains, suggest subsequently enhanced cooperativity for CoV-2. A further comparative analysis of the dynamic flexibility using the Dynamic Flexibility Index (DFI) between the CoV-1 and CoV-2 mPros shows that the inhibitor binding near active sites induces change in flexibility to a distal region of the protein, opposite in behavior between the two systems; this region becomes more flexible upon inhibitor binding in CoV-1 while it becomes less flexible in the CoV-2 mPro. Upon inspection, we show that, on average, the dynamic flexibility of the sites substituted from CoV-1 to CoV-2 changes significantly less than the average calculated across all residues within the structure, indicating that the differences in behaviors between the two systems is likely the result of allosteric influence, where the new substitutions in COV-2 induce flexibility and dynamical changes elsewhere in the structure.

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SARS-CoV-2 multi-variant graphene biosensor based on engineered dimeric ACE2 receptor -

Fast, reliable and point-of-care systems to detect the SARS-CoV-2 infection are crucial to contain viral spreading and to adopt timely clinical treatments. Many of the rapid detection tests currently in use are based on antibodies that bind viral proteins. However, newly appearing virus variants accumulate mutations in their RNA sequence and produce proteins, such as Spike, that may show reduced binding affinity to these diagnostic antibodies, resulting in less reliable tests and in the need for continuous update of the sensing systems. Here we propose a graphene field- effect transistor (gFET) biosensor which exploits the key interaction between the Spike protein and the human ACE2 receptor. This interaction is one of the determinants of host infections and indeed recently evolved Spike variants were shown to increase affinity for this receptor. Through extensive computational analyses we show that a chimeric ACE2-Fc construct mimics the ACE2 dimer, normally present on host cells membranes, better than its soluble truncated form. We demonstrate that ACE2-Fc functionalized gFET is effective for in vitro detection of Spike and outperforms the same chip functionalized with either a diagnostic antibody or the soluble ACE2. Our sensor is implemented in a portable, wireless, point-of-care device and successfully detected both alpha and gamma virus variants in patient clinical samples. As incomplete immunization, due to vaccine roll-out, may offer new selective grounds for antibody-escaping virus variants, our biosensor opens to a class of highly sensitive and variant-robust SARS-CoV-2 detection systems.

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Frequency of surveillance testing necessary to reduce transmission of the Delta variant of SARS-CoV-2 -

We estimate the reduction in transmission of SARS-CoV-2 achievable by surveillance testing of a susceptible population at different frequencies, comparing the cases of both the original Wuhan strain and the Delta variant. We estimate the viral dynamics using viral copy number at first detection combined with considerations arising from aerosol transmission. We take into account the recent findings that infected vaccinated adults may have live viral loads at the same level as infected unvaccinated adults. Our estimates suggest that twice weekly testing, which was adequate for the original strains of SARS-CoV-2 will be insufficient on its own to contain the spread of the Delta variant of concern. We exclude consideration of contact tracing since the rapidity of the onset of viral titre in the case of the Delta variant suggests that unless contact tracing and quarantine are performed very rapidly (ie. much less than a day), these mitigations will be of minimal impact in reducing transmission. These crude estimates do not take into account heterogeneity of susceptibility, social activity, and compliance, nor do they include the additional reduction in transmission that could be achieved by masking and social distancing. In the setting of a large public university, these considerations suggest that risk-targeted testing of vaccinated students, staff and faculty combined with surveillance testing of all unvaccinated individuals is the most efficient way to reduce transmission of COVID-19.

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Covid-19 Sentry

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