Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages.

KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution.

Rapid and accessible testing was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. Here, we describe our learnings and provide our blueprint for launching diagnostic laboratories, particularly in low-resource settings.

From the Editors.

It will take years before we can understand and measure the full toll that the COVID-19 pandemic has taken on our health systems. Of the many reverberations from the pandemic, one of the most concerning implications is an increase in the rates of preventable harm. Four years of unprecedented demand on healthcare services combined with health human resource shortages and clinician burnout have pushed our systems to the brink - and are impacting our capacity to improve or even maintain standards of care.

Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors.

The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both high and low passage strains of HCMV. Pre-treatment of cells with interferon alpha (IFNα) was required for robust and prolonged inhibition of both low and high passage HCMV strains, with no obvious toxicity, and was associated with an increased anti-viral state in HCMV-infected cells.

From the Editors.

As we consider the current pressures on healthcare, the options for where to focus our policy and leadership efforts are numerous and, at times, overwhelming. From health human resources capacity to access to mental health and preventative care to intermittent closures of emergency departments - the outlook is alarming. To help make sense of the situation, our editorial team carefully considers a few areas to focus on in each edition.

Differential dysregulation of β-TrCP1 and -2 by HIV-1 Vpu leads to inhibition of canonical and non-canonical NF-κB pathways in infected cells.

The HIV-1 Vpu protein is expressed late in the virus lifecycle to promote infectious virus production and avoid innate and adaptive immunity. This includes the inhibition of the NF-κB pathway which, when activated, leads to the induction of inflammatory responses and the promotion of antiviral immunity. Here we demonstrate that Vpu can inhibit both canonical and non-canonical NF-κB pathways, through the direct inhibition of the F-box protein β-TrCP, the substrate recognition portion of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex.

Shadows and Light: An Interview with Heather Patterson.

The editors of Healthcare Quarterly (HQ) recently had the opportunity to speak with Heather Patterson - emergency physician, photographer and author of the recently released book Shadows and Light (Patterson 2022). Through the photographs she took at Calgary-area hospitals during the height of the COVID-19 pandemic, Patterson created a poignant record of how the pandemic affected hospital staff, patients and their families. The book has struck a chord with many Canadians as it offers both an honest appraisal of the dreadful toll of the pandemic while also demonstrating the grace and compassion of healthcare workers.

From the Editors.

The recent winter months were particularly brutal for the healthcare system and its patients as we grappled with an onslaught of infectious diseases, healthcare backlogs and critical shortages of health human resources. We subsequently watched as Canada's federal and provincial leaders sought agreement on additional investments for several of our most precarious sectors, including long-term care, primary care and mental healthcare. Spring 2023 offers some optimism in that we will have new resources to make much-needed improvements to our depleted health sectors and services.

The ongoing Streptococcus pyogenes (Group A Streptococcus) outbreak in London, United Kingdom, in December 2022: a molecular epidemiology study.

Objectives: Epidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom).

Methods: Prospective identification of Group A Streptococcus cases from a diagnostic laboratory serving central and south London between 27 November and 10 December 2022. Case notes were reviewed and isolates were retrieved.

Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins.

Cellular antiviral factors that recognize viral nucleic acid can inhibit virus replication. These include the zinc finger antiviral protein (ZAP), which recognizes high CpG dinucleotide content in viral RNA. Here, we investigated the ability of ZAP to inhibit the replication of human cytomegalovirus (HCMV).

Pangolin merbecovirus gets down to (poly)basics.

Trafficking of live mammals is considered a major risk for emergence of zoonotic viruses. SARS-CoV-2-related coronaviruses have previously been identified in pangolins, the world's most smuggled mammal. A new study identifies a MERS-related coronavirus in trafficked pangolins with broad mammalian tropism and a newly acquired furin cleavage site in Spike.

A Nuclear Export Signal in KHNYN Required for Its Antiviral Activity Evolved as ZAP Emerged in Tetrapods.

The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic viral RNA to inhibit protein synthesis and target the RNA for degradation. ZAP evolved in tetrapods and there are clear orthologs in reptiles, birds, and mammals. When ZAP emerged, other proteins may have evolved to become cofactors for its antiviral activity.

Lessons from the COVID-19 Pandemic for Long-Term Care: Where Do We Go Next?

Even before the COVID-19 pandemic, I would often hear colleagues who are intimately familiar with our health and social care system remark that they would never allow themselves or those closest to them to end up in long-term care. Sadly, the conversation often progressed to an acknowledgment that more desirable alternatives to long-term care for the most part lie outside our publicly supported care system and are only accessible to those with the means. And then we had the pandemic.

The P681H Mutation in the Spike Glycoprotein of the Alpha Variant of SARS-CoV-2 Escapes IFITM Restriction and Is Necessary for Type I Interferon Resistance.

The appearance of new dominant variants of concern (VOC) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to the coronavirus disease 2019 (COVID-19) pandemic. Of these, the alpha variant (also known as B.1.

Real-Time Whole Genome Sequencing to Guide Patient-Tailored Therapy of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The management of coronavirus disease 2019 has become more complex due to the expansion of available therapies. The presence of severe acute respiratory syndrome coronavirus 2 variants and mutations further complicates treatment due to their differing susceptibilities to therapies. Here we outline the use of real-time whole genome sequencing to detect persistent infection, evaluate for mutations confering resistance to treatments, and guide treatment decisions.

From the Editors.

Although we do not yet know how or when the story of COVID-19 ends, Canadians are welcoming the summer of 2022 with the anticipation of the first prolonged period of near normalcy in two-and-a-half years. This sense of renewal coincides with the start of our roles as the new co-editors-in-chief of Healthcare Quarterly (HQ). Building on HQ's 25 years of excellence in sharing leading practices in health services delivery and policy, we are looking forward to taking the journal in new directions.

TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.

Ebola virus (EBOV) causes highly pathogenic disease in primates. Through screening a library of human interferon-stimulated genes (ISGs), we identified TRIM25 as a potent inhibitor of EBOV transcription-and-replication-competent virus-like particle (trVLP) propagation. TRIM25 overexpression inhibited the accumulation of viral genomic and messenger RNAs independently of the RNA sensor RIG-I or secondary proinflammatory gene expression.

Homebrew: Protocol for glassmilk-based nucleic-acid extraction for SARS-CoV-2 diagnostics.

The gold standard protocol for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detection remains reverse transcription quantitative polymerase chain reaction (qRT-PCR), which detects viral RNA more sensitively than any other approach. Here, we present Homebrew, a low-cost protocol to extract RNA using widely available reagents. Homebrew is as sensitive as commercially available RNA extraction kits.