Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection (preprint)

Background Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Methods Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). Results We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-Cindicating tubular dysfunction and injury. Conclusions Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Longitudinal Physiological Data from a Wearable Device Identifies SARS-CoV-2 Infection and Symptoms and Predicts COVID-19 Diagnosis (preprint)

Background: Changes in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with and observed prior to the clinical identification of infection. We performed an evaluation of this metric collected by wearable devices, to identify and predict Coronavirus disease 2019 (COVID-19) and its related symptoms. Methods: Health care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study App which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study measuring HRV throughout the follow up period. Surveys assessing infection and symptom related questions were obtained daily. Findings: Using a mixed-effect COSINOR model the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), a HRV metric, differed between subjects with and without COVID-19 (p=0.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (p=0.01). Significant changes in the mean MESOR and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19 related symptom compared to all other symptom free days (p=0.01). Interpretation: Longitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can identify the diagnosis of COVID-19 and COVID-19 related symptoms. Prior to the diagnosis of COVID-19 by nasal PCR, significant changes in HRV were observed demonstrating its predictive ability to identify COVID-19 infection.

Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection (preprint)

Background: The degree of myocardial injury, reflected by troponin elevation, and associated outcomes among hospitalized patients with Coronavirus Disease (COVID-19) in the US are unknown. Objectives: To describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19. Methods: Patients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value <0.03ng/mL) measured within 24 hours of admission were included (n=2,736). Demographics, medical history, admission labs, and outcomes were captured from the hospital EHR. Results: The median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. Even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were associated with death (adjusted HR: 1.77, 95% CI 1.39-2.26; P<0.001) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were associated with more pronounced risk (adjusted HR 3.23, 95% CI 2.59-4.02). Conclusions: Myocardial injury is prevalent among patients hospitalized with COVID-19, and is associated with higher risk of mortality. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation likely reflects non-ischemic or secondary myocardial injury.

Differential ventilation using flow control valves as a potential bridge to full ventilatory support during the COVID-19 crisis (preprint)

Background: It has been projected that there will be too few ventilators to meet demand during the COVID-19 (SARS CoV-2) pandemic. Ventilator sharing has been suggested as a crisis standard of care strategy to increase availability of mechanical ventilation. The safety and practicality of shared ventilation in patients is unknown. We designed and evaluated a system whereby one mechanical ventilator can be used to simultaneously ventilate two patients who have different lung compliances using a custom manufactured flow control valve to allow for individual adjustment of tidal volume and airway pressure for each patient. Methods: The system was first evaluated in a simulation lab using two human patient simulators under expected clinical conditions. It was then tested in an observational study of four patients with acute respiratory failure due to COVID-19. Two separately ventilated COVID-19 patients were connected to a single ventilator for one hour. This intervention was repeated in a second pair of patients. Ventilatory parameters (tidal volume, peak airway pressures, compliance) were recorded at five minute intervals during both studys. Arterial blood gases were taken at zero, thirty, and sixty minutes. The primary outcome was maintenance of stable acid-base status and oxygenation during shared ventilation. Results: Two male and two female patients, age range 32-56 yrs, participated. Ideal body weight and driving pressure were markedly different among patients. All patients demonstrated stable physiology and ventilation for the duration of shared ventilation. In one patient tidal volume was increased after 30 minutes to correct a respiratory acidosis. Conclusions: Differential ventilation using a single ventilator and a split breathing circuit with flow control valves is possible. A single ventilator could feasibly be used to safely ventilate two COVID-19 patients simultaneously as a bridge to full ventilatory support.