IntroductionThere is a paucity of data that can be used to guide the management of critically ill patients with COVID-19. In response, a research and data-sharing collaborative—The COVID-19 Critical Care Consortium—has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights crucial to improving outcomes.Methods and analysisThis is an international, multicentre, observational study of patients with confirmed or suspected SARS-CoV-2 infection admitted to ICUs. This is an evolving, open-ended study that commenced on 1 January 2020 and currently includes >350 sites in over 48 countries. The study enrols patients at the time of ICU admission and follows them to the time of death, hospital discharge or 28 days post-ICU admission, whichever occurs last. Key data, collected via an electronic case report form devised in collaboration with the International Severe Acute Respiratory and Emerging Infection Consortium/Short Period Incidence Study of Severe Acute Respiratory Illness networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane oxygenation and associated complications, as well as data on adjunctive therapies.Ethics and disseminationLocal principal investigators will ensure that the study adheres to all relevant national regulations, and that the necessary approvals are in place before a site may contribute data. In jurisdictions where a waiver of consent is deemed insufficient, prospective, representative or retrospective consent will be obtained, as appropriate. A web-based dashboard has been developed to provide relevant data and descriptive statistics to international collaborators in real-time. It is anticipated that, following study completion, all de-identified data will be made open access.Trial registration numberACTRN12620000421932 (http://anzctr.org.au/ACTRN12620000421932.aspx).

The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.

The acute respiratory distress syndrome (ARDS) is a severe lung disorder with a high morbidity and mortality which affects all age groups. Despite active research with intense, ongoing attempts in developing pharmacological agents to treat ARDS, its mortality rate remains unaltered high and treatment is still only supportive. Over the years, there have been many attempts to identify meaningful subgroups likely to react differently to treatment among the heterogenous ARDS population, most of them unsuccessful. Only recently, analysis of large ARDS cohorts from randomized controlled trials have identified the presence of distinct biological subphenotypes among ARDS patients: a hypoinflammatory (or uninflamed; named P1) and a hyperinflammatory (or reactive; named P2) subphenotype have been proposed and corroborated with existing retrospective data. The hyperinflammatory subphenotyope was clearly associated with shock state, metabolic acidosis, and worse clinical outcomes. Core features of the respective subphenotypes were identified consistently in all assessed cohorts, independently of the studied population, the geographical location, the study design, or the analysis method. Additionally and clinically even more relevant treatment efficacies, as assessed retrospectively, appeared to be highly dependent on the respective subphenotype. This discovery launches a promising new approach to targeted medicine in ARDS. Even though it is now widely accepted that each ARDS subphenotype has distinct functional, biological, and mechanistic differences, there are crucial gaps in our knowledge, hindering the translation to bedside application. First of all, the underlying driving biological factors are still largely unknown, and secondly, there is currently no option for fast and easy identification of ARDS subphenotypes. This narrative review aims to summarize the evidence in biological subphenotyping in ARDS and tries to point out the current issues that will need addressing before translation of biological subohenotypes into clinical practice will be possible.