BACKGROUND. Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS. A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You’an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4–7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS. We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION. Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.

Purpose: To investigate the risk factors for recurrence in patients with early-stage hepatocellular carcinoma (HCC) after minimally invasive treatment with curative intent, then to construct a prediction model based on Lasso-Cox regression and visualize the model built.Methods: Clinical data were collected from 547 patients that received minimally invasive treatment in our hospital from January 1, 2012, to December 31, 2016. Lasso regression was used to screen risk factors for recurrence. Then we established Cox proportional hazard regression model and random survival forest model including several parameters screened by Lasso regression. An optimal model was selected by comparing the values of C-index, then the model was visualized and the nomogram was finally plotted.Results: The variables screened by Lasso regression including age, gender, cirrhosis, tumor number, tumor size, platelet-albumin-bilirubin index (PALBI), and viral load were incorporated in the Cox model and random survival forest model (P<0.05). The C-index of these two models in the training sets was 0.729 and 0.708, and was 0.726 and 0.700 in the validation sets, respectively. So we finally chose Lasso-Cox regression model, and the calibration curve in the validation set performed well, indicating that the model built has a better predictive ability. And then a nomogram was plotted based on the model chosen to visualize the results.Conclusions: The present study established a nomogram for predicting recurrence in patients with early-stage HCC based on the Lasso-Cox regression model. This nomogram was of some guiding significance for screening populations at high risk of recurrence after treatment, by which doctors can formulate individualized follow-up strategies or treatment protocols according to the predicted risk of relapse for patients to improve the long-term prognosis.

Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction.

The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support. Herein, the hypothesis that hepatocellular carcinoma (HCC) leaves a molecular signature in the host peripheral immune system was tested by profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets (n = 80 and n = 48) using pyrosequencing. The study reveals a broad signature of hepatocellular carcinoma in PBMC and T cells DNA methylation which discriminates early HCC stage from chronic hepatitis B and C and healthy controls, intensifies with progression of HCC, and is highly enriched in immune function-related genes such as PD-1, a current cancer immunotherapy target. These data also support the feasibility of using these profiles for early detection of HCC.

Background: Monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment. The aim of this study was to elucidate the effect of MLR and subsequent MLR when relapse occurred (R-MLR) on prognosis for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) combined with ablation. Methods: A prospective analysis was conducted on 606 patients with HCC who were treated with TACE combined with local ablation in Beijing You’an Hospital affiliated to Capital Medical University from January 1, 2012 to December 31, 2016. MLR or R-MLR were stratified according to the optimal cut-off values. The cumulative recurrence-free survival (RFS), overall survival (OS) , and recurrence-death survival (RDS) rates were calculated by Kaplan–Meier method. The Cox proportion hazard model and logistic regression analysis was conducted to screen for independent predictive factors for indicating early relapse and long-term prognosis. Results: High MLR was significantly associated with relapse, early recurrence, and overall survival. After a median follow-up of 59.4 months, The cumulative 1-, 3-, 5-year RFS rates of low MLR were 74.6%, 43.8%, and 34.0%; while 66.1%, 32.2%, and 22.6% for high group (P < 0.001). There were also significant differences in corresponding OS rates of the two groups (P = 0.003). The cumulative 1-, 3-, 5-year OS rates of low R-MLR were 99.5%, 87.2%, 75.5%; while 98.3%, 78.3%, 61.7% for high group (P < 0.001). There were also significant differences in corresponding RDS rates in the two groups (P = 0.008). 436 patients were divided into four groups on the base of cut-off values of MLR and R-MLR (low-low, low–high, high-low, and high-high). The low-low group has shown better outcomes including the cumulative 1-, 3-, 5-year OS, and RDS rates(P < 0.001). Conclusions: High MLR was related to unfavorable outcome. Subsequent change of MLR between baseline and HCC relapse could indicate poor long-term survival after relapse.

Introduction: Locoregional interventional therapy including transcatheter arterial chemoembolization (TACE) and ablation are the current standard of treatment for early-to-mid-stage hepatocellular carcinoma (HCC). However, questions remain unanswered regarding the management of recurrence after locoregional treatment. PD-1 inhibitors can block inhibitory signals of T-cell activation and proliferation to reduce the recurrence. We conducted a single-arm phase 2 trial to evaluate the efficacy and safety of PD-1 inhibitors following locoregional interventional therapy in HCC patients with high recurrence risk guided by our novel scoring system.Methods: Patients enrolled initially treated by TACE combined with ablation, then willingly joined the experimental group. One month later, they received the anti-PD-1 adjuvant therapy (intravenous injection of 200 mg), which was repeated every 3 weeks for a total of 4 or 8 cycles. Within this same period, other patients were screened into the control group to match the experimental group by 1:1 based on the propensity score matching method (PSM). The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS) recurrence modality, safety, and quality of life.Result: At the time of data cutoff, the median RFS of the control group was 7.0 months while the experimental group had not reached it. Moreover, the 1-year RFS rate was 73.3% in the experimental group and 46.7% in the control group, showing a significant difference (P =0.02). The rate of local tumor progression in the experimental group was clearly lower than that in the control group (P = 0.027). Benefits associated with anti-PD-1 adjuvant therapy were observed in patients with multiple tumors and tumor size ≤2cm. Univariate and multivariate analyses demonstrated that anti-PD-1 adjuvant therapy was an independent favorable prognostic factor for RFS in HCC patients. The most frequent AE observed in this study was RCCEP, and other AEs included diarrhea, hepatotoxicity, rash, pruritus, and fatigue. The incidence of GRADE ≥3 AE and withdrawal in this study was low with no deaths recorded.Conclusions: Interim analysis from the study suggest the addition of anti-PD-1 adjuvant therapy after TACE combined with ablation could significantly prolong RFS with controllable safety for early-to-mid-stage HCC patients with high recurrence risk.