Real-time estimation of immunological responses against emerging SARS-CoV-2 variants in the UK: a mathematical modelling study.

Background: The emergence of SARS-CoV-2 variants and COVID-19 vaccination have resulted in complex exposure histories. Rapid assessment of the effects of these exposures on neutralising antibodies against SARS-CoV-2 infection is crucial for informing vaccine strategy and epidemic management. We aimed to investigate heterogeneity in individual-level and population-level antibody kinetics to emerging variants by previous SARS-CoV-2 exposure history, to examine implications for real-time estimation, and to examine the effects of vaccine-campaign timing.

An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization.

Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth.

Levels of Influenza A Virus Defective Viral Genomes Determine Pathogenesis in the BALB/c Mouse Model.

Defective viral genomes (DVGs), which are generated by the viral polymerase in error during RNA replication, can trigger innate immunity and are implicated in altering the clinical outcome of infection. Here, we investigated the impact of DVGs on innate immunity and pathogenicity in a BALB/c mouse model of influenza virus infection. We generated stocks of influenza viruses containing the internal genes of an H5N1 virus that contained different levels of DVGs (indicated by different genome-to-PFU ratios).

Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection.

Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain.

The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets.

SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2' cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture-adapted SARS-CoV-2 virus with an S1/S2 deletion, we show that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impairs replication in Vero E6, a cell line used for passaging SARS-CoV-2.

Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia.

COVID-19 is a disease with unique characteristics that include lung thrombosis, frequent diarrhoea, abnormal activation of the inflammatory response and rapid deterioration of lung function consistent with alveolar oedema. The pathological substrate for these findings remains unknown. Here we show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation.

Latent Cytomegalovirus Infection and Previous Capsular Polysaccharide Vaccination Predict Poor Vaccine Responses in Older Adults, Independent of Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines.

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study.

Objective: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2-React 2).

Design: Diagnostic accuracy study.

Setting: Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London.

Handheld Point-of-Care System for Rapid Detection of SARS-CoV-2 Extracted RNA in under 20 min.

The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (<20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples.

Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study.

Background: Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.

Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey.

Background: Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients.

Comparison of single radial immunodiffusion, SDS-PAGE and HPLC potency assays for inactivated influenza vaccines shows differences in ability to predict immunogenicity of haemagglutinin antigen.

The current gold-standard potency test for inactivated influenza vaccines is the single radial immunodiffusion (SRD) assay. A number of alternative potency tests for inactivated influenza vaccines have been proposed in recent years. Evaluation of these new potency tests commonly involves comparison with SRD, in order to ascertain that the new method obtains values that correlate with those measured by the standard potency test.

Ambivalence about supervised injection facilities among community stakeholders.

Background: Community stakeholders express a range of opinions about supervised injection facilities (SIFs). We sought to identify reasons for ambivalence about SIFs amongst community stakeholders in two Canadian cities.

Findings: We used purposive sampling methods to recruit various stakeholder representatives (n = 141) for key informant interviews or focus group discussions.

Establishing expertise: Canadian community-based medical cannabis dispensaries as embodied health movement organisations.

In this commentary, I describe how, through both advocacy and the generation of new knowledge, community-based medical cannabis dispensaries have contributed to the broader dialogue regarding the legal and safe provision of medical cannabis in Canada. By employing an embodied health movement framework (Brown et al., 2004), this analysis highlights the role of dispensaries in creating new knowledge, challenging existing practices, and advancing their agenda to legitimise cannabis as a therapeutic substance and offer an alternative model for its provision.

Design considerations for supervised consumption facilities (SCFs): preferences for facilities where people can inject and smoke drugs.

Background: Supervised consumption facilities (SCFs) aim to improve the health and well-being of people who use drugs by offering safer and more hygienic alternatives to the risk environments where people typically use drugs in the community. People who smoke crack cocaine may be willing to use supervised smoking facilities (SSFs), but their facility design preferences and the views of other stakeholders have not been previously investigated in detail.

Methods: We consulted with people who use drugs and other stakeholders including police, fire and ambulance service personnel, other city employees and city officials, healthcare providers, residents, and business owners (N = 236) in two Canadian cities without SCFs and asked how facilities ought to be designed.

Police perceptions of supervised consumption sites (SCSs): a qualitative study.

Police are key stakeholders in cities considering supervised consumption site (SCS) implementation. We examine police perceptions of SCSs using data collected between 2008 and 2010. Data from interviews and focus groups conducted with police officers of varied ranks (n = 18) in Ottawa and Toronto, Canada, were analyzed using thematic analyses.