Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19 (preprint)

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

SARS-COV2 Renal Impairment in Critical Care: A Retrospective Study of 42 Cases - Kid COVID Study (preprint)

BackgroundThe new coronavirus (SARS-CoV-2) infection leads to 5% to 16% hospitalization in Intensive Care Units (ICU) and is associated with 23% to 75% of kidney impairments, including acute kidney injury (AKI), as a major prognosis factor. The current work aims to characterize the renal impairment associated to SARS-CoV-2 in ICU patients, to evaluate its risk factors and its relationship with morbidity and mortality. Methods Forty-two patients consecutively admitted to the ICU of a university hospital (Paris, France) who tested positive for SARS-CoV-2 between March 25, 2020 and April 29, 2020 were included and classified in categories according to their renal function. Complete renal profiles and their evolution during ICU stay were fully characterized in 34 patients. Factors associated with AKI were identified through univariate analysis.ResultsThirty-two patients (94,1%) met diagnostic criteria for intrinsic renal injury with a mixed pattern of tubular and glomerular injuries within the first week of ICU admission, that lasted upon discharge. During their ICU stay, 24 patients (57.1%) presented AKI which was associated with increased mortality (p = 0.007), hemodynamic failure (p = 0.022), and more altered clearance at hospital discharge (p = 0.001). AKI occurrence was associated with lower pH (p = 0.024), higher PaCO2 (p = 0.027), PEEP (p = 0.027), procalcitonin (p = 0.015), and CRP (p = 0.045) on ICU admission.ConclusionsCritical SARS-CoV-2 is associated with persistent intrinsic renal injury and AKI, which is a risk factor of mortality. Identifying SARS-CoV-2 patients at risk of AKI will help in modifying clinical practice in ICU. Trial registration In accordance with the French law on biomedical research, this study obtained the approval of an Institutional Review Board (“Comité d’Éthique de la Recherche en Anesthésie-Réanimation” under the reference IRB 00010254 ‐ 2020 ‐ 106). Patients were all informed of the possible use of their data in researches as well as their right and terms of objection. Data were collected and integrated anonymously into a secure database in accordance with the French CNIL MR-004 methodology (registration number 20200803123416).