Intensity-Based Computation Tomography (CT) Evaluation of Temporal Changes in Lung Abnormalities During the Recovery Stage in COVID-19 In-Hospital Patients (preprint)

Background: The coronavirus disease-19 (COVID-19) and its variants have increased rapidly worldwide since December 2019, with respiratory disease being a prominent complication. As such, optimizing evaluation methods and identifying factors predictive of disease progress remain critical. The purpose of the study was to assess late phase (≥3 weeks) pulmonary changes using intensity-based computed tomography (CT) scoring in COVID-19 patients and determine the clinical characteristics predicting lung abnormalities and recovery. Methods: : We conducted a retrospective study on 42 patients (14 males, 28 females; age 65±10 years) with COVID-19. Only patients with at least 3 CT scans taken at least 3 weeks after initial symptom onset were included in the study. Two scoring methods were assessed: (1) area-based scoring (ABS) and (2) intensity-weighted scoring (IWS). Temporal changes in the average lung lesion were evaluated by the calculating the averaged area under the curve (AUC) of the CT score-time curve. Correlations between averaged AUCs and clinical characteristics were determined. Results: Using the ABS system, temporal changes in lung abnormalities during recovery were highly variable (P=0.934). By contrast, the IWS system detected more subtle changes in lung abnormalities during in COVID-19 patients, with consistent week-to-week relative reductions in IWS (P=0.025). Strong relationships were observed with D-dimer and C-reactive protein (CRP) levels on admission, with hazard ratios (HR)(95%CI) of 5.32 (1.25-22.6)(P=0.026) and 1.05 (1.10-1.09)(P=0.017), respectively. Conclusion: Our results suggest COVID-19-mediated pulmonary abnormalities persist well-beyond 3-weeks of symptom onset, with intensity-weighted rather than area-based scoring being more sensitive. Moreover, D-dimer and CRP levels were predictive of the recovery from the disease.

IL-6 and D-Dimer at Admission Predicts Cardiac Injury and Early Mortality during SARS-CoV-2 Infection (preprint)

BACKGROUND We recently described mortality of cardiac injury in COVID-19 patients. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiacinjury and mortality patterns in COVID-19 is unknown. METHODS This retrospective cohort study included 170 COVID-19 patients with cardiac injury at admission to Tongji Hospital in Wuhan from January 29–March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death were elevate levels of interleukin 6 (IL-6) (p<0.0001), Tumor Necrosis Factor-a (TNF-a) (p=0.0025), and C-reactive protein (CRP) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic pathway activation. Increasing cTnI levels were associated with those of increasing IL-6 (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS In COVID-19 patients with cardiac injury, admission IL-6 and D-dimer predicted subsequent elevation of cTnI and early death, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury. Condensed Abstract COVID-19 with cardiac injury is associated with worse survival. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiac injury and mortality patterns in COVID-19 is unknown. This study proved that cardiac injury in these patients is closely related to the activation of immunological and thrombotic pathways and can be predicted by admission biomarkers of these pathways. This study supports the strategy of biomarker-guided, point-of-care therapy that warrants further studies in a randomized manner to develop anti-immune and anti-thrombotic treatment regimens in severe COVID-19 patients with cardiac injury.

Computation Tomography (CT)-Based Evaluation of Temporal Changes in Lung Abnormalities During the Recovery Stage in COVID-19 In-Hospital Patients (preprint)

Objectives: To assess the late phase CT changes of COVID-19 patients, and figure out factors predicting lung abnormality in late phase.Methods: We conducted a retrospective study on 42 patients (14 males, 28 females; age 65±10 years) with COVID-19 admitted between February 7, 2020 and March 27, 2020. Only patients with at least 3 CT scans taken at least 3 weeks after initial symptom onset were included in the study. CT images were analyzed by 2 independent radiologists using different scoring: (1) area-based scoring (ABS); and (2) intensity-weighted scoring (IWS). Temporal changes in the average lung lesion were evaluated by averaged area under the curve (AUC) of the CT score-time curve. Correlations between averaged AUCs and clinical characteristics were determined. Results: Temporal changes in lung abnormalities during recovery (weeks 3 through 8) of CT findings using the ABS system were variable (P=0.934). By contrast, the IWS system detected more subtle changes in lung abnormalities during the late phase of recovery in COVID-19 patients, with consistent week-to-week relative reductions in IWS (P=0.025). In assessing the correlation between averaged AUCs and clinical characteristics, strong relationships were observed with D-dimer and C-reactive protein (CRP) levels on admission, with hazard ratios (HR)(95%CI) of 5.32 (1.25-22.6)(P=0.026) and 1.05 (1.10-1.09)(P=0.017), respectively. Conclusion: Our results suggest an intensity-weighted rather than area-based scoring system is more sensitive to detect subtle temporal CT changes in COVID-19, with D-dimer and CRP levels on admission being predictive of the time course of late phase recovery from the disease.

Modulation of Cardiac Injury by ACE inhibitor/ARB in Patients with Severe COVID-19 (preprint)

Introduction: Cardiac injury occurs in 7-22% of patient hospitalized with COVID-19 and an elevation in troponin is associated with a 4.2-fold increase in the risk of mortality. Preliminary data showed ACEi/ARB usage might not increase mortaily in COVID-19 patients. However, it is unknown if cardiac injury in patients with severe COVID-19 can be modulated by ACEi/ARB usage during evolution of the cardiac injury.Methods: In 154 COVID-19 patients with cardiac injury, the effect of ACEi/ARB treatment (17 patients) was compared with 137 patients without ACEi/ARB treatment. Cardiac injury was indicated by cTnI level.Results: In ACEi/ARB treatment group and no ACEi/ARB treatment group, peak cTnI level did not show significant difference (150.5 pg/ml [31.75-1179], vs 207 pg/ml [54.65-989.4], respectively, P = 0.21). Evolution of Cardiac injury (temporal change of cTnI at day 6, 9, 12, 15, 18, 21, 24, 27, 30, and 33) showed no statistical difference. Mortality (ACEi/ARB group vs no ACEi/ARB group; 52.9% vs 69.9%, P = 0.17), atrial arrhythmias (11.7% vs 24.4%, P = 0.36), requirement for invasive ventilatory support (29.4% vs 48.2%, P = 0.14) also showed no significant difference in two groups.Conclusions: ACEi/ARB usage during the COVID-19 was not associated with exacerbation of cardiac injury. These data should be interpreted as essentially hypothesis-generating due to small sample size.Clinical Trial Registration: This retrospective study was registered in Chinese clinical trial registry (ChiCTR 2000031301).