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Background: Pulmonary embolism (PE) is a well-recognised complication of coronavirus disease 2019 (COVID-19) infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established., Methods: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post-hospital discharge according to existing risk scores using symptoms, ECG and N-terminal pro-brain natriuretic peptide., Results: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month; p=0.252). Of 334 confirmed CTEPD/CTEPH cases, four (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further three (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT., Conclusion: A priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation., Competing Interests: Conflict of interest: J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell; received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon; and is Chief Editor of the European Respiratory Journal. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Objective: Prospectively validate prognostication scores, SOARS and 4C Mortality Score, derived from the COVID-19 first wave, for mortality and safe early discharge in the evolving pandemic with SARS-CoV-2 variants (B.1.1.7 replacing D614) and healthcare responses altering patient demographic and mortality., Design: Protocol-based prospective observational cohort study., Setting: Single site PREDICT and multisite ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts in UK COVID-19 second wave, October 2020 to January 2021., Participants: 1383 PREDICT and 20 595 ISARIC SARS-CoV-2 patients., Primary Outcome Measures: Relevance of SOARS and 4C Mortality Score determining in-hospital mortality and safe early discharge in the evolving UK COVID-19 second wave., Results: 1383 (median age 67 years, IQR 52-82; mortality 24.7%) PREDICT and 20 595 (mortality 19.4%) ISARIC patient cohorts showed SOARS had area under the curve (AUC) of 0.8 and 0.74, while 4C Mortality Score had AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore, effective in evaluating safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with SOARS of 0-1 were candidates for safe discharge to a virtual hospital (VH) model. SOARS implementation in the VH pathway resulted in low readmission, 11.8% (27/229) and low mortality, 0.9% (2/229). Use to prevent admission is still suboptimal, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1., Conclusions: SOARS and 4C Mortality Score remains valid, transforming complex clinical presentations into tangible numbers, aiding objective decision making, despite SARS-CoV-2 variants and healthcare responses altering patient demographic and mortality. Both scores, easily implemented within urgent care pathways for safe early discharge, allocate hospital resources appropriately to the pandemic's needs while enabling normal healthcare services resumption., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2-6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2)., Methods and Analysis: Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2-6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections., Ethics and Dissemination: This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies., Competing Interests: Competing interests: CWT and LFW received a patent for the development of the cPass SARS-CoV-2 Neutralization Antibody Detection Kit used in the study. CYS, YW, SYC and YW are employed by EVYD Technology, who is the provider for the BruHealth and EVYDResearch platforms., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Outbreaks of the COVID-19 pandemic caused by the SARS-CoV-2 infection that started in Wuhan, China, have quickly spread worldwide. The current situation has contributed to a dynamic rate of hospital admissions. Global efforts by Artificial Intelligence (AI) and Machine Learning (ML) communities to develop solutions to assist COVID-19-related research have escalated ever since. However, despite overwhelming efforts from the AI and ML community, many machine learning-based AI systems have been designed as black boxes. This paper proposes a model that utilizes Formal Concept Analysis (FCA) to explain a machine learning technique called Long-short Term Memory (LSTM) on a dataset of hospital admissions due to COVID-19 in the United Kingdom. This paper intends to increase the transparency of decision-making in the era of ML by using the proposed LSTM-FCA explainable model. Both LSTM and FCA are able to evaluate the data and explain the model to make the results more understandable and interpretable. The results and discussions are helpful and may lead to new research to optimize the use of ML in various real-world applications and to contain the disease., Competing Interests: Declaration of Competing Interest Nurul Saleh reports financial support was provided by University of Malaysia Kelantan., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods., Competing Interests: Author CS is a part-time employee of EVYD Technology Limited which was the technology partner and research collaborator of this study. EVYD Technology Limited is the developer of EVYDResearch, BruHealth and EVYDENCE platforms. SC, YWe, YWa, AL, and HL are full-time employees of EVYD Technology Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shim, Chan, Wei, Ghani, Ahmad, Sharif, Alikhan, Haji Bagol, Taib, Tan, Ong, Wang, Wang, Liu, Lim, Wong, Naing and Cunningham.)

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies., Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure., Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021., Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475)., Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days., Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group., Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings., Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Objectives: To investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity., Design: A retrospective observational case-control study looking at serum calcium on adult patients with COVID-19, and community-acquired pneumonia (CAP) or viral pneumonia (VP)., Setting: A district general hospital on the outskirts of London, UK., Participants: 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP., Outcome Measures: Baseline characteristics including hypocalcaemia in patients with COVID-19, CAP and VP were detailed. For patients with COVID-19, the impact of an abnormally low calcium level on the maximum level of hospital care, as a surrogate of COVID-19 severity, was evaluated. The primary outcome of maximal level of care was based on the WHO Clinical Progression Scale for COVID-19., Results: Hypocalcaemia was a specific and common clinical finding in patients with COVID-19 that distinguished it from other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with OR of 2.33 (95% CI 1.5 to 3.61) for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by days 7-9 of admission, only in survivors of COVID-19., Conclusion: Hypocalcaemia is specific to COVID-19 and may help distinguish it from other infective pneumonias. Hypocalcaemia may independently predict severe disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease., Trial Registration Number: 20/HRA/2344., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Multiple mini-interview (MMI) is a 'multiple sample-based' approach comprising multiple focused encounters intended to access and assess a range of attributes in order to gain more objectively multiple impressions of an applicant's interpersonal skills, thoughtfulness and general demeanour. It is designed to focus on four domains that are not considered to be comprehensive, but are considered to be vital for a successful career in the health sciences: critical thinking, ethical decision making, communication and knowledge of the healthcare system. Traditionally, the MMI is conducted face-to-face, but with COVID-19 pandemic and the implementation of social distancing measures, no onsite or campus teaching, banning of mass gatherings and cancellation of face-to-face interviews, Pengiran Anak Puteri Rashidah Sa'adatul Bolkiah Institute of Health Sciences at Universiti Brunei Darussalam explored the feasibility of conducting MMI through virtual means. This report provides an account of our experience in conducting internet-MMI for the selection of new applicants into the August 2020 cohort of the Medicine programme. We also aimed to determine whether the scores derived from internet-MMI were reliable and equivalent to the scores derived from traditional MMI.