Incidence of Respiratory Pathogens in Naval Special Warfare SEAL Candidates with Swimming-Induced Pulmonary Edema.

BACKGROUND: Swimming-Induced Pulmonary Edema (SIPE) is a respiratory condition frequently seen amongst Naval Special Warfare (NSW) trainees. The incidence of positive respiratory panels (RPs) in trainees diagnosed with SIPE is currently unknown. RESEARCH QUESTION: Is there a significant difference in the incidence of respiratory pathogens in nasopharyngeal samples of NSW candidates with SIPE and a control group? STUDY DESIGN AND METHODS: Retrospective analysis of clinical information from NSW Sea Air and Land (SEAL) candidates diagnosed with SIPE over a 12-month period. Candidates who presented with the common signs and symptoms of SIPE received a nasopharyngeal swab and RP test for common respiratory pathogens. SIPE diagnoses were supported by two-view chest radiograph. RP tests were obtained for a selected control group of 1st phase trainees without SIPE. RESULTS: 45 of 1048 SEAL candidates were diagnosed with SIPE (4.3%). 5 had superimposed pneumonia. 36 of 45 tested positive for at least one microorganism on the RP (80%). In the study group, human rhinovirus/enterovirus (RV/EV) was the most frequently detected organism (37.8%), followed by coronavirus OC43 (17.8%), and parainfluenza virus 3 (17.8%). 16 of 68 candidates from the control group had positive RPs (24%). Patients with SIPE and positive RPs reported dyspnea (94%), pink-frothy sputum (44%), and hemoptysis (22%) more frequently than the controls with positive RPs. Those who reported respiratory infection symptoms in both the study and control groups had higher incidences of positive RPs (P=.046). INTERPRETATION: We observed that 80% of trainees diagnosed with SIPE tested positive on a point of care RP. This positivity rate was significantly higher than RP test results from the control cohort. These findings suggest an association between colonization with a respiratory pathogen and the development of SIPE in NSW candidates.

Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial.

BACKGROUND: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug. METHODS: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test. RESULTS: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort. CONCLUSIONS: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.

Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial.

INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL. METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board. ETHICS AND DISSEMINATION: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION NUMBER: NCT04842448.

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.

Diving after SARS-CoV-2 (COVID-19) infection: Fitness to dive assessment and medical guidance.

Scuba diving is a critical activity for commercial industry, military activities, research, and public safety, as well as a passion for many recreational divers. Physicians are expected to provide return-to-diving recommendations after SARS-CoV-2 (COVID-19) infection based upon the best available evidence, often drawn from experience with other, similar diseases. Scuba diving presents unique physiologic challenges to the body secondary to immersion, increased pressure and increased work of breathing. The long-term sequelae of COVID-19 are still unknown, but if they are proven to be similar to other coronaviruses (such as Middle East respiratory syndrome or SARS-CoV-1) they may result in long-term pulmonary and cardiac sequelae that impact divers' ability to safely return to scuba diving. This review considers available literature and the pathophysiology of COVID-19 as it relates to diving fitness, including current recommendations for similar illnesses, and proposes guidelines for evaluation of divers after COVID-19. The guidelines are based upon best available evidence about COVID-19, as well as past experience with determination of diving fitness. It is likely that all divers who have contracted COVID-19 will require a medical evaluation prior to return to diving with emphasis upon pulmonary and cardiac function as well as exercise capacity.

Can hyperbaric oxygen safely serve as an anti-inflammatory treatment for COVID-19?

INTRODUCTION: SARS-CoV-2 affects part of the innate immune response and activates an inflammatory cascade stimulating the release of cytokines and chemokines, particularly within the lung. Indeed, the inflammatory response during COVID-19 is likely the cause for the development of acute respiratory distress syndrome (ARDS). Patients with mild symptoms also show significant changes on pulmonary CT-scan suggestive of severe inflammatory involvement. HYPOTHESIS: The overall hypothesis is that HBO2 is safe and reduces the inflammatory response in COVID-19 pneumonitis by attenuation of the innate immune system, increase hypoxia tolerance and thereby prevent organ failure and reduce mortality. EVALUATION OF THE HYPOTHESIS: HBO2 is used in clinical practice to treat inflammatory conditions but has not been scientifically evaluated for COVID-19. Experimental and empirical data suggests that HBO2 may reduce inflammatory response in COVID-19. However, there are concerns regarding pulmonary safety in patients with pre-existing viral pneumonitis. EMPIRICAL DATA: Anecdotes from "compassionate use" and two published case reports show promising results. CONSEQUENCES OF THE HYPOTHESIS AND DISCUSSION: Small prospective clinical trials are on the way and we are conducting a randomized clinical trial.