28 May, 2021

What happened to drug detections and drug-offences during the early months of the COVID-19 pandemic: A comparison of recorded offence rates and dynamic forecasts (ARIMA) in Queensland, Australia -

Public commentary has offered mixed opinion on the likely impact of COVID-19 restrictions on drug-related offending. On the one hand, it is argued that drug users—and the drug markets in which they interact—may have become the incidental targets of law enforcement as police seek to enforce social distancing regulations by focusing their efforts on street-level pedestrian activity or open-air gatherings. On the other, interstate border closures and restrictions on person and freight traffic are thought to have interrupted illicit drug supply chains, temporarily reducing or displacing market activity at the street level and thus reducing police detections of drug users. In this study, we extend current analyses of crime during the COVID-19 pandemic to explore how the rate of police detection for drug possession and other drug-related offences has changed. Using Queensland crime data, we use Auto-Regressive and Moving Average (ARIMA) time series modelling techniques to explore historical trends and their dynamic forecasts. We then compare actual offence rates for March through June to identify any statistically significant changes. Importantly, we do not expect the impact of COVID-19 regulations to be universal, mostly because of the significant heterogeneity in local drug market dynamics that has elsewhere been documented. Our analysis has significant import for criminal justice practitioners in further understanding drug market dynamics and drug-related offending during COVID-19 restrictions.

🖺 Full Text HTML: What happened to drug detections and drug-offences during the early months of the COVID-19 pandemic: A comparison of recorded offence rates and dynamic forecasts (ARIMA) in Queensland, Australia

Portable and label-free quantitative Loop-mediated Isothermal Amplification (qLAMP) for reliable COVID-19 diagnostics in 3 minutes: An Arduino-based detection system assisted by a pH microelectrode -

Loop-mediated isothermal amplification (LAMP) has been recently studied as an alternative method for cost-effective diagnostics in the context of the current COVID-19 pandemic. Recent reports document that LAMP-based diagnostic methods have a comparable sensitivity and specificity to that of RT-qPCR. We report the use of a portable Arduino-based LAMP-based amplification system assisted by pH microelectrodes for the accurate and reliable diagnosis of SARS-CoV-2 during the first 3 minutes of the amplification reaction. We show that this simple system enables a straightforward discrimination between samples containing or not containing artificial SARS-CoV-2 genetic material in the range of 10 to 10,000 copies per 50 μL of reaction mix. We also spiked saliva samples with SARS-CoV-2 synthetic material and corroborated that the LAMP reaction can be successfully monitored in real time using microelectrodes in saliva samples as well. These results may have profound implications for the design of real-time and portable quantitative systems for the reliable detection of viral pathogens including SARS-CoV-2.

🖺 Full Text HTML: Portable and label-free quantitative Loop-mediated Isothermal Amplification (qLAMP) for reliable COVID-19 diagnostics in 3 minutes: An Arduino-based detection system assisted by a pH microelectrode

Mortality audit of cancer patients with SARS-CoV-2 positivity or COVID-19 -

Coronavirus disease-2019 (COVID-19) has disrupted cancer care services globally. The present review of cause of deaths was conducted in a tertiary care cancer center in the North East India. In our institute, all cancer patients requiring admission for surgery, chemotherapy, and other daycare procedures require testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). From 09 July 2020 to 16 May 2021, 119 cancer patients with SARS-CoV-2 positive report or COVID-19 have been admitted at our institute Covid ward. A total of 19 cancer patients with COVID-19 succumbed. Of 19 deaths, 13 (68.4%) patients were men and 6 (31.6%) patients were women. The age range from 27 years to 74 years (median =55 years). Vomiting alone or with diarrhea was the most common symptom requiring admission after testing (4/19, 21.0%), followed by bleeding from primary tumour site (3/19, 15.7%). The antecedent and underlying cause of deaths in 19 (100%) patients was cancer. SARS-CoV-2 infection should not be a hindrance for cancer treatment and management.

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Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada -

Objectives: To estimate the effectiveness of one and two doses of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design: Using a test-negative design study and linked laboratory, vaccination, and health administrative databases, we estimated adjusted vaccine effectiveness (aVE) against symptomatic infection and severe outcomes (hospitalization or death) using multivariable logistic regression. Setting: Ontario, Canada between 14 December 2020 and 19 April 2021. Participants: Community-dwelling adults aged ≥16 years who were tested for SARS-CoV-2 and had COVID-19 symptoms. Interventions: Pfizer-BioNTech9s BNT162b2 or Moderna9s mRNA-1273 vaccine. Main outcome measures: Laboratory-confirmed SARS-CoV-2 identified by RT-PCR; hospitalization or death associated with SARS-CoV-2 infection. Results: Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received 1 or more vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. aVE against symptomatic infection 14 days or more after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14-20 days after the first dose to 71% (95%CI, 63 to 78%) at 35-41 days. aVE 7 days or more after receiving 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, aVE 14 days or more after receiving 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14-20 days to 91% (95%CI, 73 to 97%) at 35 days or more, whereas aVE 7 days or more after receiving 2 doses was 98% (95%CI, 88 to 100%). For adults aged 70 years and older, aVE estimates were lower after receiving 1 dose, but were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants. Conclusions: Two doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and severe outcomes. Effectiveness is lower after only a single dose, particularly for older adults shortly after the first dose.

🖺 Full Text HTML: Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada

Vaccine-Hesitant Parents’ Considerations Regarding Covid-19 Vaccination of Adolescents -

Introduction: Israel led a rapid vaccine rollout against COVID-19, leading to a local remission of the epidemic and rolling back of most public health measures. Further vaccination of 12-15-year-olds may be hindered by public perceptions of the necessity and safety of vaccination. Methods: we examined the considerations of vaccine hesitant parents (VHPs) regarding vaccination of children against COVID-19. The responses of 456 parents were surveyed and analyzed before FDA authorization of vaccination of children. Results: parents who were vaccinated against COVID-19 were more likely to intend to vaccinate their children (r=-0.466, p<0.01). Low accessibility of vaccination may be a dissuading factor for VHPs more inclined to vaccinate. Vaccine efficacy and gaining a “Green Pass” were positively associated with an intention to vaccinate and statistically significant. VHPs inclined not to vaccinate indicated short development time and possible long term effects as dissuading factors. Discussion: vaccine promotion should be tailored for VHPs9 positive and negative considerations for higher uptake.

🖺 Full Text HTML: Vaccine-Hesitant Parents’ Considerations Regarding Covid-19 Vaccination of Adolescents

Exploring the natural origins of SARS-CoV-2 in the light of recombination -

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (Sarbecoviruses) have been identified, is fuelling speculation on the natural origins of SARS-CoV-2. We have comprehensively analysed phylogenetic relations between SARS-CoV-2, and the related bat and pangolin Sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Clustering of the inferred recombination events is non-random with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift in the ancestry of bat Sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm horseshoe bats, Rhinolophus, are the likely SARS-CoV-2 progenitor reservoir species. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and co-circulation of these viruses’ ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years or so. We confirm that a direct proximal ancestor to SARS-CoV-2 is yet to be sampled, since the closest relative shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for more wildlife sampling to (i) pinpoint the exact origins of SARS-CoV-2’s animal progenitor, and (ii) survey the extent of the diversity in the related Sarbecoviruses’ phylogeny that present high risk for future spillover.

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Portable real-time colorimetric LAMP-device for rapidquantitative detection of nucleic acids in crude samples -

Loop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting substances. We developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative molecular diagnosis with the simplicity of point-of-care testing. This handheld device employs a single reaction pot for amplification and a mini-camera for detection. Competitive features are the rapid analysis (<30min), quantification over 9 log-units, crude sample compatibility (saliva, tissue, swabs), low detection limit (<5copies/reaction), smartphone operation and fast prototyping (3D printing). The devices clinical utility is demonstrated in cancer mutations and COVID-19 testing. Excellent performance includes: detection of 0.01% of BRAF-V600E-to-wild-type molecules; 97% sensitivity to SARS-CoV-2 RNA detection (89 samples); 83% (Ct<34), 98% (Ct<30) and 100% (Ct<25) to 163 nasopharyngeal swabs; 100% specificity in all cases. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.

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Single-Molecule Dynamics of SARS-CoV-2 5’ Cap Recognition by Human eIF4F -

Coronaviruses initiate translation through recognition of the viral RNA 5’ m7GpppAm cap by translation factor eIF4F. eIF4F is a heterotrimeric protein complex with cap-binding, RNA-binding, and RNA helicase activities. Modulating eIF4F function through cellular regulation or small-molecule inhibition impacts coronavirus replication, including for SARS-CoV-2. Translation initiation involves highly coordinated dynamics of translation factors with messenger or viral RNA. However, how the eIF4F subunits coordinate on the initiation timescale to define cap-binding efficiency remains incompletely understood. Here we report that translation supported by the SARS-CoV-2 5’ UTR is highly sensitive to eIF4A inhibition by rocaglamide. Through a single-molecule fluorescence approach that reports on eIF4E-cap interaction, we dissect how eIF4F subunits contribute to cap-recognition efficiency on the SARS-CoV-2 5’ UTR. We find that free eIF4A enhances cap accessibility for eIF4E binding, but eIF4G alone does not change the kinetics of eIF4E-RNA interaction. Conversely, formation of the full eIF4F complex significantly alters eIF4E-cap interaction, suggesting that coordinated eIF4E and eIF4A activities establish the net eIF4F-cap recognition efficiency. Moreover, the eIF4F complex formed with phosphomimetic eIF4E(S209D) binds the viral UTR more efficiently than with wild-type eIF4E. These results highlight a dynamic interplay of eIF4F subunits and mRNA that determines cap-recognition efficiency.

🖺 Full Text HTML: Single-Molecule Dynamics of SARS-CoV-2 5’ Cap Recognition by Human eIF4F

An altered metabolism in leukocytes showing in vitro igG memory from SARS-CoV-2-infected patients -

Coronavirus disease 2019 (COVID 19) is a systemic infection that exerts a significant impact on cell metabolism. In this study we performed metabolomic profiling coupled with multivariate statistics analysis obtained from 43 in vitro cultures of peripheral blood mononuclear cells (PBMC), 19 of which displaying IgG memory for spike-S1 antigen 60-90 days after infection. By using mass spectrometry analysis, a significant up regulation of S-adenosyl-Homocysteine, Sarcosine and Arginine was found in leukocytes showing IgG memory. These metabolites are known to be involved in physiological recovering from viral infections and immune activities, and our findings might represent a novel and easy measure that could be of help in understanding SARS-Cov-2 effects on leukocytes.

🖺 Full Text HTML: An altered metabolism in leukocytes showing in vitro igG memory from SARS-CoV-2-infected patients

The anti SARS-Cov-2 Vaccines And The Questions They Raise -

Since it was first reported in late 2019, SARS-Cov-2 had a global impact on human physical and mental health, as well as on their social life and economic endeavor. In one year, the virus has infected over 115 million people, killed almost 2.6 million of them and left many others with long-term health sequelae. The SARS-Cov-2 pandemic has overwhelmed healthcare systems, interrupted routine care and prevented patients’ follow-up. All these factors led to increased mortality from other chronic diseases. Further, the SARS-Cov-2 pandemic has caused an unprecedented disruption to education, economic trade, travel, social life, and has profoundly changed our way of living. In this review article we present the organization and the function of the immune system that protects us against diseases, the virology, the infection, the transmission and the pathogenesis of SARS-Cov-2, the disease Covid-19, the development of vaccines against SARS-Cov-2 and some of the questions raised by these vaccines, as well as suggested responses to them.

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Liberating host-virus knowledge from biological dark data -

Connecting basic data about bats and other potential hosts of SARS-CoV-2 with their ecological context is critical for understanding the emergence and spread of COVID-19. However, when global lockdown started in March 2020, the world’s bat experts were locked out of their research laboratories, which, in turn, locked up large volumes of offline ecological and taxonomic data. Pandemic lockdowns have put a magnifying glass on the long-standing problem of biological ‘dark data’: data which are published, but disconnected from digital knowledge resources, and thus unavailable for high-throughput analysis. Knowledge of host-to-virus ecological interactions will be biased until this challenge is addressed. Here we outline two viable solutions: (i) how to interconnect published data about host organisms, viruses, and other pathogens in the short term; and (ii) how to shift the publishing paradigm beyond unstructured text (‘PDF prison’) to labeled networks of digital knowledge. Biological taxonomy is foundational to both solutions as the indexing system for biodiversity data. Building digitally connected ‘knowledge graphs’ of host-pathogen interactions will establish the needed agility for quickly identifying reservoir hosts of novel zoonoses, allow for more robust predictions of emergence, and thereby strengthen planetary health systems.

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Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients -

Several studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specific Angpt2 knockout mice. Using in vitro assays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection.

🖺 Full Text HTML: Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals -

The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

🖺 Full Text HTML: Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101 -

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins’ ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil -defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific - and {theta}-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

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A new method to study genome mutations using the information entropy -

We report a non-clinical, mathematical method of studying genetic sequences based on the information theory. Our method involves calculating the information entropy spectrum of genomes by splitting them into windows containing a fixed number of nucleotides. The information entropy value of each window is computed using the m-block information entropy formula. We show that the information entropy spectrum of genomes contains sufficient information to allow detection of genetic mutations, as well as possibly predicting future ones. Our study indicates that the best m-block size is 2 and the optimal window size should contain more than 9, and less than 33 nucleotides. In order to implement the proposed technique, we created specialized software, which is freely available. Here we report the successful test of this method on the reference RNA sequence of the SARS-CoV-2 virus collected in Wuhan, Dec. 2019 (MN908947) and one of its randomly selected variants from Taiwan, Feb. 2020 (MT370518), displaying 7 mutations.

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