Indicators of recent COVID-19 infection status: findings from a large occupational cohort of staff and postgraduate research students from a UK university.

BACKGROUND: Researchers conducting cohort studies may wish to investigate the effect of episodes of COVID-19 illness on participants. A definitive diagnosis of COVID-19 is not always available, so studies have to rely on proxy indicators. This paper seeks to contribute evidence that may assist the use and interpretation of these COVID-indicators. METHODS: We described five potential COVID-indicators: self-reported core symptoms, a symptom algorithm; self-reported suspicion of COVID-19; self-reported external results; and home antibody testing based on a 'lateral flow' antibody (IgG/IgM) test cassette. Included were staff and postgraduate research students at a large London university who volunteered for the study and were living in the UK in June 2020. Excluded were those who did not return a valid antibody test result. We provide descriptive statistics of prevalence and overlap of the five indicators. RESULTS: Core symptoms were the most common COVID-indicator (770/1882 participants positive, 41%), followed by suspicion of COVID-19 (n = 509/1882, 27%), a positive symptom algorithm (n = 298/1882, 16%), study antibody lateral flow positive (n = 124/1882, 7%) and a positive external test result (n = 39/1882, 2%), thus a 20-fold difference between least and most common. Meeting any one indicator increased the likelihood of all others, with concordance between 65 and 94%. Report of a low suspicion of having had COVID-19 predicted a negative antibody test in 98%, but positive suspicion predicted a positive antibody test in only 20%. Those who reported previous external antibody tests were more likely to have received a positive result from the external test (24%) than the study test (15%). CONCLUSIONS: Our results support the use of proxy indicators of past COVID-19, with the caveat that none is perfect. Differences from previous antibody studies, most significantly in lower proportions of participants positive for antibodies, may be partly due to a decline in antibody detection over time. Subsequent to our study, vaccination may have further complicated the interpretation of COVID-indicators, only strengthening the need to critically evaluate what criteria should be used to define COVID-19 cases when designing studies and interpreting study results.

A Novel Intraoperative Ultrasound Probe for Transsphenoidal Surgery: First-in-human study.

Background. Ultrasound has been explored as an alternative, less bulky, less time-consuming and less expensive means of intraoperative imaging in pituitary surgery. However, its use has been limited by the size of its probes relative to the transsphenoidal corridor. We developed a novel prototype that is more slender than previously reported forward-viewing probes and, in this report, we assess its feasibility and safety in an initial patient cohort. Method. The probe was integrated into the transsphenoidal approach in patients with pituitary adenoma, following a single-centre prospective proof of concept study design, as defined by the Innovation, Development, Exploration, Assessment and Long-Term Study (IDEAL) guidelines for assessing innovation in surgery (IDEAL stage 1 - Idea phase). Results. The probe was employed in 5 cases, and its ability to be used alongside the standard surgical equipment was demonstrated in each case. No adverse events were encountered. The average surgical time was 20 minutes longer than that of 30 contemporaneous cases operated without intraoperative ultrasound. Conclusion. We demonstrate the safety and feasibility of our novel ultrasound probe during transsphenoidal procedures to the pituitary fossa, and, as a next step, plan to integrate the device into a surgical navigation system (IDEAL Stage 2a - Development phase).

Trajectories of mental health among UK university staff and postgraduate students during the pandemic.

OBJECTIVES: The COVID-19 pandemic has disrupted the social and working lives of many. Past studies have highlighted worsening mental health during the pandemic, but often rely on small samples or infrequent follow-up. This study draws on fortnightly assessments from a large occupational cohort to describe differing trajectories of mental health between April 2020 and April 2021 and individual characteristics associated with these trajectory types. METHODS: King's College London Coronavirus Health and Experiences of Colleagues at King's is an occupational cohort study at a large university in London, UK. Participants (n=2241) completed online questionnaires fortnightly between April 2020 and April 2021. Symptoms of anxiety and depression were assessed using Generalised Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). RESULTS: On average, participants reported low levels of anxiety and depression (GAD-7 and PHQ-9 scores of 0-9, consistent with 'none', 'minimal' or 'mild' symptoms) throughout the year, with symptoms highest in April 2020 and decreasing over the summer months when no lockdown measures were in place. However, we observed more severe and variable symptoms among subgroups of participants. Four trajectory types for anxiety and depression were identified: 'persistent high severity' (6%-7% of participants), 'varying symptoms, opposing national cases' (4%-8%), 'varying symptoms, consistent with national cases' (6%-11%) and 'persistent low severity' (74%-84%). Younger age, female gender, caring responsibilities and shielding were associated with higher severity trajectory types. CONCLUSIONS: These data highlight differing individual responses to the pandemic and underscore the need to consider individual circumstances when assessing and treating mental health. Aggregate trends in anxiety and depression may hide greater variation and symptom severity among subgroups.

OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator.

BACKGROUND: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). METHODS: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing. FINDINGS: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support. INTERPRETATION: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale. FUNDING: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University.