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.

Profiling serum immunodominance following SARS-CoV-2 primary and breakthrough infection reveals distinct variant-specific epitope usage and immune imprinting.

Over the course of the COVID-19 pandemic, variants have emerged with increased mutations and immune evasive capabilities. This has led to breakthrough infections (BTI) in vaccinated individuals, with a large proportion of the neutralizing antibody response targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike glycoprotein. Immune imprinting, where prior exposure of the immune system to an antigen can influence the response to subsequent exposures, and its role in a population with heterogenous exposure histories has important implications in future vaccine design.

Evaluating the dynamics of hospital COVID-19 contacts and subsequent conversion to SARS-CoV-2 infection: a multi-centre retrospective cohort study.

We investigated the dynamics of COVID-19 contacts subsequent conversion to SARS-CoV-2 infection in an inpatient setting across three National Health Service (NHS) Trusts. 9.2% (476/5,156) COVID-19 contacts met inclusion criteria, were typable and tested positive for COVID-19.

A Multinational Case Series Describing Successful Treatment of Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection Caused by Omicron Sublineages With Prolonged Courses of Nirmatrelvir/Ritonavir.

The optimum treatment for persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not known. Our case series, across 5 hospitals in 3 countries, describes 11 cases where persistent SARS-CoV-2 infection was successfully treated with prolonged courses (median, 10 days [range, 10-18 days]) of nirmatrelvir/ritonavir (Paxlovid). Most cases (9/11) had hematological malignancy and 10 (10/11) had received CD20-depleting therapy.

sp. nov., a novel species isolated from an infected prosthetic aortic graft in a human.

A novel bacterial strain, GSTT-20 was isolated from an infected, prosthetic endovascular graft explanted from a shepherd in London, United Kingdom. This strain was an aerobic, catalase-positive, oxidase-negative, Gram-stain-negative, motile, curved rod. It grew on blood agar, chocolate agar and MacConkey agar incubated at 37 °C in an aerobic environment after 48 h, appearing as yellow, mucoid colonies.

Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London.

Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection.

With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level.

Feasibility and clinical utility of local rapid Nanopore influenza A virus whole genome sequencing for integrated outbreak management, genotypic resistance detection and timely surveillance.

Rapid respiratory viral whole genome sequencing (WGS) in a clinical setting can inform real-time outbreak and patient treatment decisions, but the feasibility and clinical utility of influenza A virus (IAV) WGS using Nanopore technology has not been demonstrated. A 24 h turnaround Nanopore IAV WGS protocol was performed on 128 reverse transcriptase PCR IAV-positive nasopharyngeal samples taken over seven weeks of the 2022-2023 winter influenza season, including 25 from patients with nosocomial IAV infections and 102 from patients attending the Emergency Department. WGS results were reviewed collectively alongside clinical details for interpretation and reported to clinical teams.

A framework for real-time monitoring, analysis and adaptive sampling of viral amplicon nanopore sequencing.

The ongoing SARS-CoV-2 pandemic demonstrates the utility of real-time sequence analysis in monitoring and surveillance of pathogens. However, cost-effective sequencing requires that samples be PCR amplified and multiplexed barcoding onto a single flow cell, resulting in challenges with maximising and balancing coverage for each sample. To address this, we developed a real-time analysis pipeline to maximise flow cell performance and optimise sequencing time and costs for any amplicon based sequencing.

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.

Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals.

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve).

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.

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT).

Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.

Objective: To characterise the clinical features of monkeypox infection in humans.

Design: Descriptive case series.

Setting: A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022.

Clinical features and management of human monkeypox: a retrospective observational study in the UK.

Background: Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals.

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.

Objectives: Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings.

Design: Multicentre, prospective, interventional, superiority study.

VirA+EmiC project: Evaluating real-world effectiveness and sustainability of integrated routine opportunistic hepatitis B and C testing in a large urban emergency department.

Innovative testing approaches and care pathways are required to meet global hepatitis B virus (HBV) and hepatitis C virus (HCV) elimination goals. Routine blood-borne virus (BBV) testing in emergency departments (EDs) in high-prevalence areas is suggested by the European Centre for Disease Prevention and Control (ECDC) but there is limited evidence for this. Universal HIV testing in our ED according to UK guidance has been operational since 2015.

Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals.

Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called "hybrid immunity" leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19-vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19-double-vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the Delta (B.

Descriptive comparison of admission characteristics between pandemic waves and multivariable analysis of the association of the Alpha variant (B.1.1.7 lineage) of SARS-CoV-2 with disease severity in inner London.

Background: The Alpha variant (B.1.1.