Randomised, controlled, open label, multicentre clinical trial to explore safety and efficacy of hyperbaric oxygen for preventing ICU admission, morbidity and mortality in adult patients with COVID-19.

INTRODUCTION: COVID-19 may cause severe pneumonitis and trigger a massive inflammatory response that requires ventilatory support. The intensive care unit (ICU)-mortality has been reported to be as high as 62%. Dexamethasone is the only of all anti-inflammatory drugs that have been tested to date that has shown a positive effect on mortality. We aim to explore if treatment with hyperbaric oxygen (HBO) is safe and effective for patients with severe COVID-19. Our hypothesis is that HBO can prevent ICU admission, morbidity and mortality by attenuating the inflammatory response. The primary objective is to evaluate if HBO reduces the number of ICU admissions compared with best practice treatment for COVID-19, main secondary objectives are to evaluate if HBO reduces the load on ICU resources, morbidity and mortality and to evaluate if HBO mitigates the inflammatory reaction in COVID-19. METHODS AND ANALYSIS: A randomised, controlled, phase II, open label, multicentre trial. 200 subjects with severe COVID-19 and at least two risk factors for mortality will be included. Baseline clinical data and blood samples will be collected before randomisation and repeated daily for 7 days, at days 14 and 30. Subjects will be randomised with a computer-based system to HBO, maximum five times during the first 7 days plus best practice treatment or only best practice treatment. The primary endpoint, ICU admission, is defined by criteria for selection for ICU. We will evaluate if HBO mitigates the inflammatory reaction in COVID-19 using molecular analyses. All parameters are recorded in an electronic case report form. An independent Data Safety Monitoring Board will review the safety parameters. ETHICS AND DISSEMINATION: The trial is approved by The National Institutional Review Board in Sweden (2020-01705) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative and any inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION: NCT04327505. EudraCT number: 2020-001349-37.

Differential trends of admissions in accident and emergency departments during the COVID-19 pandemic in Germany.

BACKGROUND: Recent studies have shown a decrease of admissions to accident and emergency (A&E) departments after the local outbreaks of COVID-19. However, differential trends of admission counts, for example according to diagnosis, are less well understood. This information is crucial to inform targeted intervention. Therefore, we aimed to compare admission counts in German A&E departments before and after 12th march in 2020 with 2019 according to demographic factors and diagnosis groups. METHODS: Routine data of all admissions between 02.12.2019-30.06.2020 and 01.12.2018-30.06.2019 was available from six hospitals in five cities from north-western, eastern, south-eastern, and south-western Germany. We defined 10 diagnosis groups using ICD-10 codes: mental disorders due to use of alcohol (MDA), acute myocardial infarction (AMI), stroke or transient ischemic attack (TIA), heart failure, pneumonia, chronic obstructive pulmonary disease (COPD), cholelithiasis or cholecystitis, back pain, fractures of the forearm, and fractures of the femur. We calculated rate ratios comparing different periods in 12.03.2020-30.06.2020 with 12.03.2019-30.06.2019. RESULTS: Forty-one thousand three hundred fifty-three cases were admitted between 12.03.2020-30.06.2020 and 51,030 cases between 12.03.2019-30.06.2019. Admission counts prior to 12.03. were equal in 2020 and 2019. In the period after 12.03., the decrease of admissions in 2020 compared to 2019 was largest between 26.03. and 08.04. (- 30%, 95% CI - 33% to - 27%). When analysing the entire period 12.03.-30.06., the decrease of admissions was heterogeneous among hospitals, and larger among people aged 0-17 years compared to older age groups. In the first 8 weeks after 12.03., admission counts of all diagnoses except femur fractures and pneumonia declined. Admissions with pneumonia increased in this early period. Between 07.05. and 30.6.2020, we noted that admissions with AMI (+ 13%, 95% CI - 3% to + 32%) and cholelithiasis or cholecystitis (+ 20%, 95% CI + 1% to + 44%) were higher than in 2019. CONCLUSIONS: Our results suggest differential trends of admission counts according to age, location, and diagnosis. An initial decrease of admissions with MDA, AMI, stroke or TIA, heart failure, COPD, cholelithiasis or cholecystitis, and back pain imply delays of emergency care in Germany. Finally, our study suggests a delayed increase of admissions with AMI and cholelithiasis or cholecystitis.