Safety and immunogenicity of COVID-19 vaccination in patients with hepatocellular carcinoma (CHESS-NMCID 2101): A multicenter prospective study.

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.

Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study.

BACKGROUND: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. METHODS: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. RESULTS: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child-Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. CONCLUSIONS: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child-Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Prognostic Nomogram on Admission Predicting Progression for Patients with Nonsevere COVID-19

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019 (COVID-19) who progressed from the nonsevere condition on admission to severe during hospitalization. This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10, 2020 to Feb 7, 2020. In the training cohort, independent risk factors associated with disease progression were identified by univariate and multivariate analyses. The prognostic nomogram was established and then validated externally using C-index. The study included 351 patients (293 and 58 in the training and validation cohorts, respectively), with 27 (9.2%) and 5 (8.6%) patients progressed, respectively. In the training cohort, older age (OR 1.036, 95% CI 1.000-1.073), more lobes involved on chest CT (OR 1.841, 95% CI 1.117-3.035), comorbidity present (OR 2.478, 95% CI 1.020-6.018), and lower lymphocyte count (OR 0.081, 95% CI 0.019-0.349) were identified as independent risk factors. The prognostic nomogram was established in the training cohort with satisfied external prognostic performance (C-index 0.906, 95% CI 0.806-1.000). In conclusion, older age, comorbidity present, more lobes involved on chest CT, and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

The Landscape of Coronavirus Disease 2019 (COVID-19) and Integrated Analysis SARS-CoV-2 Receptors and Potential Inhibitors in Lung Adenocarcinoma Patients.

The outbreak of novel coronavirus disease 2019 (COVID-19) has become the largest health threat worldwide, with more than 34.40 million positive cases and over 1.02 million deaths confirmed. In this study, we confirmed that significantly differentially expressed genes in COVID-19 patients were mainly involved in the regulation of immune and inflammation-related signaling pathways. It is worth noting that many infected COVID-19 patients have malignant tumors, and their prognosis is poor. To explore the susceptibility factors of cancer patients, we assessed the expression of ACE2, TMPRSS2, and the endocytic regulator AAK1 in lung adenocarcinoma (LUAD) patients and explored their effects on immune infiltration. We found that the expression of ACE2 and TMPRSS2 in LUAD patients was significantly increased, which may explain why LUAD patients are susceptible to SARS-CoV-2, and the patients with high-expression genes presented increased infiltration of immune cells such as B cells and CD4 T cells. In addition, we also identified miR-432-5p as a potential targeted molecule and bexarotene as a potential targeted drug of the three genes through bioinformatic analysis and further verified the anti-inflammatory effect of bexarotene, providing new ideas for the treatment of COVID-19.

One-step rapid quantification of SARS-CoV-2 virus particles via low-cost nanoplasmonic sensors in generic microplate reader and point-of-care device.

The spread of SARS-CoV-2 virus in the ongoing global pandemic has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemic. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. As low as 370 vp/mL were detected in one step within 15 min and the virus concentration can be quantified linearly in the range of 0 to 107 vp/mL. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.

Machine learning-based CT radiomics method for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: a multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global challenge since the December 2019. The hospital stay is one of the prognostic indicators, and its predicting model based on CT radiomics features is important for assessing the patients' clinical outcome. The study aimed to develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with COVID-19 pneumonia. METHODS: This retrospective, multicenter study enrolled patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images from 5 designated hospitals in Ankang, Lishui, Lanzhou, Linxia, and Zhenjiang between January 23, 2020 and February 8, 2020. Patients were classified into short-term (≤10 days) and long-term hospital stay (>10 days). CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features from pneumonia lesions in first four centers. The predictive performance was evaluated in fifth center (test dataset) on lung lobe- and patients-level. RESULTS: A total of 52 patients were enrolled from designated hospitals. As of February 20, 21 patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in analysis. The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with COVID-19 pneumonia, with areas under the curves of 0.97 (95% CI, 0.83-1.0) and 0.92 (95% CI, 0.67-1.0) by LR and RF, respectively, in test. The LR and RF model showed a sensitivity and specificity of 1.0 and 0.89, 0.75 and 1.0 in test respectively. As of February 28, a prospective cohort of six discharged patients were all correctly recognized as long-term stay using RF and LR models. CONCLUSIONS: The machine learning-based CT radiomics features and models showed feasibility and accuracy for predicting hospital stay in patients with COVID-19 pneumonia.