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The achievements realized in the last year of coronavirus disease 2019 (COVID-19) research are nothing short of astonishing; the virus was sequenced, clinical tests were established, the epidemiology was characterized, numerous therapeutics were tested, and a number of different vaccines were developed and approved. Gains that would typically take years were realized in months, with progress documented through tens of thousands of scholarly publications disseminated globally, most of them available for free. This impressive rate of progress has also been evident in research directed specifically toward COVID-19 in its most severe form, with the global critical care community embarking on an unprecedented, coordinated project to generate new insights into the biology, treatment, and prevention of life-threatening COVID-19. These efforts rapidly generated evidence that has already changed practice. The Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial provided rapid, emphatic evidence that hydroxychloroquine (1) and lopinavirritonavir (2) were ineffective, and then that dexamethasone could reduce the risk of death in the sickest patients (3). Randomized, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) confirmed that another steroid, hydrocortisone, was also effective (4) and then discovered persuasive evidence of benefit from specific inhibitors of interleukin-6 (5). We learned that other treatments such as systemic anticoagulation and interferon therapy (5) may be harmful in this group but could confer benefit in those less sick. We also learned that the propensity to develop severe COVID19 was associated with clinical risk factors like age, hypertension, and diabetes (6–8), as well as specific genetic features related to innate viral defences and lung inflammation (9–11). Just as stunning as the speed of discovery in the COVID-19 era is its stark contrast with the era of critical care that preceded it. Prior to 2020, randomized trials in the ICU showing a significant difference between treatment groups were very much the exception, rather than the rule. Paradoxically, many of these studies were done in the very syndromes that characterize severe COVID-19, namely sepsis and the acute respiratory distress syndrome (ARDS). Why have these syndromes, so long resistant to the identification of effective treatments, suddenly given way to a wellspring of definitive results? We suggest that recent successes are the result of two key factors: the biological homogeneity of severe, late-stage COVID-19, and the unprecedented international collaboration enabling recruitment at scale. The first of these considerations speaks to a growing recognition that critical illness syndromes are biologically heterogeneous (12–14). Evidence of subtypes in these conditions is rapidly mounting, including in sepsis (15–18), ARDS (19–21), David M. Maslove, MD, MS1–3