a patient in his 30s admitted to the intensive care unit (ICU) in Codogno Hospital (Lodi, Lombardy, Italy) tested positive for a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 . He had a history of atypical pneumonia that was not responding to treatment, but he was not considered at risk for COVID-19 infection. 1 The positive result was immediately reported to the Lombardy health care system and governmental offices. During the next 24 hours, the number of reported positive cases increased to 36. This situation was considered a serious development for several reasons: the patient ("patient 1") was healthy and young; in less than 24 hours, 36 additional cases were identified, without links to patient 1 or previously identified positive cases already in the country; it was not possible to identify with certainty the source of transmission to patient 1 at the time; and, because patient 1 was in the ICU and there were already 36 cases by day 2, chances were that a cluster of unknown magnitude was present and additional spread was likely.On February 21, an emergency task force was formed by the Government of Lombardy and local health authorities to lead the response to the outbreak. This Viewpoint provides a summary of the response of the COVID-19 Lombardy ICU network and a forecast of estimated ICU demand over the coming weeks (projected to March 20, 2020).

IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.