Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.

Phase 2a randomised, placebo-controlled, double-blinded, trial.

Hospitals in Canada, Turkey and the USA.

A total of 61 subjects with moderate-to-severe COVID-19.

Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.

The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.

At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O₂ ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.

In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.

NCT04402957.

To understand and report on the direct-to-consumer virtual care industry in Canada, focusing on how companies collect, use and value patient data.

Qualitative study using situational analysis methodology.

Canadian for-profit virtual care industry.

18 individuals employed by or affiliated with the Canadian virtual care industry.

Semistructured interviews were conducted between October 2021 and January 2022 and publicly available documents on websites of commercial virtual care platforms were retrieved. Analysis was informed by situational analysis, a constructivist grounded theory methodology, with a continuous and iterative process of data collection and analysis; theoretical sampling and creation of theoretical concepts to explain findings.

Participants described how companies in the virtual care industry highly valued patient data. Companies used data collected as patients accessed virtual care platforms and registered for services to generate revenue, often by marketing other products and services. In some cases, virtual care companies were funded by pharmaceutical companies to analyse data collected when patients interacted with a healthcare provider and adjust care pathways with the goal of increasing uptake of a drug or vaccine. Participants described these business practices as expected and appropriate, but some were concerned about patient privacy, industry influence over care and risks to marginalised communities. They described how patients may have agreed to these uses of their data because of high levels of trust in the Canadian health system, problematic consent processes and a lack of other options for care.

Patients, healthcare providers and policy-makers should be aware that the direct-to-consumer virtual care industry in Canada highly values patient data and appears to view data as a revenue stream. The industry’s data handling practices of this sensitive information, in the context of providing a health service, have implications for patient privacy, autonomy and quality of care.

Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.

This double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.

Ethical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.

NCT05870150

To prevent the spread of infectious disease, children are typically asked not to attend school, clubs or other activities, or socialise with others while they have specific symptoms. Despite this, many children continue to participate in these activities while symptomatic.

We commissioned a national cross-sectional survey with data collected between 19 November and 18 December 2021.

Eligible parents (n=941) were between 18 and 75 years of age, lived in the UK and had at least one child aged between 4 and 17 years. Parents were recruited from a pre-existing pool of potential respondents who had already expressed an interest in receiving market research surveys.

Parents were asked whether their children had exhibited either recent vomiting, diarrhoea, high temperature/fever, a new continuous cough, a loss or change to their sense of taste or smell in the absence of a negative (PCR) COVID-19 test (‘stay-at-home symptoms’) since September 2021 and whether they attended school, engaged in other activities outside the home or socialised with members of another household while symptomatic (‘non-adherent’). We also measured parent’s demographics and attitudes about illness.

One-third (33%, n=84/251, 95% CI: 28% to 39%) of children were ‘non-adherent’ in that they had attended activities outside the home or socialised when they had stay-at-home symptoms. Children were significantly more likely to be non-adherent when parents were aged 45 and younger; they allowed their children to make their own decisions about school attendance; they agreed that their child should go to school if they took over-the-counter medication; or they believed that children should go to school if they have mild symptoms of illness.

To reduce the risk of spreading disease, parents and teenagers need guidance to help them make informed decisions about engaging in activities and socialising with others while unwell.