Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge (preprint)

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.

Reducing intravenous monoclonal antibody observation times without compromising patient safety;a single-centre observational study

IntroductionMonoclonal antibodies (MAbs) are integral to manage Inflammatory Bowel Disease (IBD). At Brighton & Sussex University Hospital, intravenous MAbs, infliximab and vedolizumab, are administered in an outpatient setting. Licensing specifies post-infusion observation times of 1 to 2 hours. This affects waiting lists and capacity.MethodsA single-centre observation study was conducted.Part 1Retrospective data was collected for all infliximab and vedolizumab infusions from April to July 2019. Patients seen twice, were included once. For established infusion patients, historical reactions were recorded. Reaction incidence was established by observations, patient questioning and record review.To standardise the reactions, we used the cancer Common Terminology Criteria for Adverse Events;grade 3 is ‘severe’.Part 2Observation time was removed from infusion 4 in April 2020. Prospective data was collected for all infliximab and vedolizumab infusions from April to December 2020. Multiple attendances were included.ResultsPart 1130 infliximab patients (2607 infusions) and 69 vedolizumab patients (557 infusions) were reviewed.No severe reactions were recorded. All reactions occurred during induction. Analysis showed high levels of ‘no reactions observed’ after the first 4 infliximab infusions 97.7% (+1.6%, -4.7%), and the first 3 vedolizumab infusions 96.9% (+2.3%, -8.8%).121 hours could be saved for infliximab and 64 hours for vedolizumab. Extrapolated this equates to 740 hours per year.Part 2679 infliximab infusions were administered (including 12 new starters). 418 vedolizumab infusions were administered (16 new starters). No reactions were reported.Absreact PMO-9 Table 1 Pt Inf Reactions Inf Occurrence Grade Symptoms Management MAb Stopped IINFLIXIMAB Part 1 Induct 130 2607 3 (0.12%) 1 2 Itching Chlorphenamine IV No 2 2 Flushing & chest tightness Hydrocortisone IV, chlorphenamine IV + paracetamol PO Yes 3 2 Shortness of breath Chlorphenamine IV No Maint 121 2583 0 - - - - - Part 2 - NC 679 0 - - - - - VEDOLIZUMAB Part 1 Induct 69 557 1 (0.18%) 1 1 Headache Paracetamol PO No Maint 64 550 0 - - - - - Part 2 - NC 418 0 - - - - - Key: Pt – patients, Inf – infusions, MAb – monoclonal antibody, Induct – Induction, Maint – maintenance, IV – intravenous, PO – oral, NC – not collectedConclusionsAll infusion reactions occurred within 3 infusions, were non-severe and managed in clinic. By removing observation periods from infusion 4, capacity increased in concordance with COVID-19 social distancing, without affecting waiting times or patient safety. Patient experience was anecdotally improved. Further data from other centres are required to prove significance.

Testing for SARS-CoV-2 in care home staff and residents in English care homes: A service evaluation (preprint)

Background COVID-19 has especially affected care home residents. Aim To evaluate a nurse-led Enhanced Care Home Team (ECHT) enhanced SARS-CoV-2 testing strategy. Design and setting Service evaluation in care homes in Norfolk UK. Method Residents and staff received nose and throat swab tests (7 April to 29 June 2020). Resident test results were linked with symptoms on days 0-14 after test and mortality to 13 July 2020. Results Residents (n=518) in 44 homes and staff (n=340) in 10 care homes were tested. SARS-CoV-2 positivity was identified in 103 residents in 14 homes and 49 staff in seven homes. Of 103 SARS-CoV-2+ residents, just 38 had typical symptom(s) at time of test (new cough and/or fever). Amongst 54 residents who were completely asymptomatic when tested, 12 (22%) developed symptoms within 14 days. Compared to SARS-CoV-2 negative residents, SARS-CoV-2+ residents were more likely to exhibit typical symptoms (new cough (n=26, p=0.001); fever (n=24, p=<0.001)) or as generally-unwell (n=18, p=0.001). Of 38 resident deaths, 21 (55%) were initially attributed to SARS-CoV-2, all of whom tested SARS-CoV-2+. One death not initially attributed to SARS-CoV-2 also tested positive. Conclusion Testing identified asymptomatic and pre-symptomatic SARS-CoV-2+ residents and staff. Being generally-unwell was common amongst symptomatic residents and may indicate SARS-CoV-2 infection in older people in the absence of more typical symptoms. Where a resident appears generally unwell SARS-CoV-2-infection should be suspected. Protocols for testing involved integrated health and social care teams.

Social media and smartphone app use predicts maintenance of physical activity during Covid-19 enforced isolation in psychiatric outpatients (preprint)

Public health professionals have raised concerns that the social and physical distancing measures implemented in response to the Covid-19 pandemic may negatively impact health in other areas, via both decreased physical activity and increased social isolation. Here, we investigated whether increased engagement with digital social tools may help mitigate effects of enforced isolation on physical activity and mood, in a naturalistic study of at-risk individuals. Passively sensed smartphone app use and actigraphy data, collected from a sample of psychiatric outpatients both before and during imposition of strict lockdown conditions (N=163), were analysed using Gaussian graphical models: a form of network analysis which gives insight into the predictive relationships between measures across timepoints. Within-individuals, we found evidence of a positive predictive path between digital social engagement, general smartphone use, and physical activity - selectively under lockdown conditions. Further, we observed a positive relationship between social media use and total daily steps across individuals during (but not prior to) lockdown. We interpret these findings in terms of individuals using these digital tools to harness online social support structures, which may help guard against negative effects of in-person social deprivation and other pandemic-related stress. Monitoring of these measures is low burden and unintrusive and therefore, given appropriate consent, could potentially help identify individuals who are failing to engage this mechanism, providing a route to early intervention in this and other vulnerable populations.