Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis.

BACKGROUND: An effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown. METHODS: Seventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method. RESULTS: We observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability. CONCLUSION: This study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.

Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis

Background An effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown. Methods Seventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method. Results We observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability. Conclusion This study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.

Stretchable, self‐healable, and breathable biomimetic iontronics with superior humidity‐sensing performance for wireless respiration monitoring

Stretchable, self‐healing, and breathable skin‐biomimetic‐sensing iontronics play an important role in human physiological signal monitoring and human–computer interaction. However, previous studies have focused on the mimicking of skin tactile sensing (pressure, strain, and temperature), and the development of more functionalities is necessary. To this end, a superior humidity‐sensitive ionic skin is developed based on a self‐healing, stretchable, breathable, and biocompatible polyvinyl alcohol–cellulose nanofibers organohydrogel film, showing a pronounced thickness‐dependent humidity‐sensing performance. The as‐prepared 62.47‐μm‐thick organohydrogel film exhibits a high response (25,000%) to 98% RH, excellent repeatability, and long‐term stability (120 days). Moreover, this ionic skin has excellent resistance to large mechanical deformation and damage, and the worn‐out material can still retain its humidity‐sensing capabilities after self‐repair. Humidity‐sensing mechanism studies show that the induced response is mainly related to the increase of proton mobility and interfacial charge transport efficiency after water adsorption. The superior humidity responsiveness is attributed to the reduced thickness and the increased specific surface area of the organohydrogel film, allowing real‐time recording of physiological signals. Notably, by combining with a self‐designed printed circuit board, a continuous and wireless respiration monitoring system is developed, presenting its great potential in wearable and biomedical electronics.

Deep Mobile Linguistic Therapy for Patients with ASD.

Autistic spectrum disorder (ASD) is one of the most complex groups of neurobehavioral and developmental conditions. The reason is the presence of three different impaired domains, such as social interaction, communication, and restricted repetitive behaviors. Some children with ASD may not be able to communicate using language or speech. Many experts propose that continued therapy in the form of software training in this area might help to bring improvement. In this work, we propose a design of software speech therapy system for ASD. We combined different devices, technologies, and features with techniques of home rehabilitation. We used TensorFlow for Image Classification, ArKit for Text-to-Speech, Cloud Database, Binary Search, Natural Language Processing, Dataset of Sentences, and Dataset of Images with two different Operating Systems designed for Smart Mobile devices in daily life. This software is a combination of different Deep Learning Technologies and makes Human-Computer Interaction Therapy very easy to conduct. In addition, we explain the way these were connected and put to work together. Additionally, we explain in detail the architecture of software and how each component works together as an integrated Therapy System. Finally, it allows the patient with ASD to perform the therapy anytime and everywhere, as well as transmitting information to a medical specialist.

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.

Prognostic significance of day-by-day in-hospital blood pressure variability in COVID-19 patients with hypertension.

Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID-19) and increases in-hospital mortality. Day-by-day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID-19 patients with hypertension. This study aimed to demonstrate whether day-by-day in-hospital BPV had prognostic significance in these patients. The authors included 702 COVID-19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in-hospital BP measurements on at least seven consecutive days. Day-by-day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID-19 and non-survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C-reactive protein, procalcitonin, high-sensitive cardiac troponin I, and B-type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05-1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01-1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day-by-day in-hospital SBP variability can independently predict mortality and ARDS in COVID-19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients.

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.

Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants.

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.

Correlation of hypocalcemia with poor prognosis of COVID-19 based on cox regression model: an analysis of 2 651 patients

ObjectiveTo investigate whether hypocalcemia is associated with poor prognosis in COVID-19 patients. MethodsA retrospective analysis was performed on 2 651 COVID-19 patients admitted to Wuhan Huoshenshan Hospital from February 4, 2020 to April 11, 2020. They were divided into low and normal calcium groups according to their serum calcium level lower than 2.11 mmol/L or not. Their basic demographic characteristics, results of laboratory tests, treatment, complications and outcomes were analyzed and compared between the 2 groups. COX regression model was used to analyze whether low calcium is an independent risk factors for poor outcomes in COVID-19 patients. ResultsThe low calcium group had significantly higher ratios of mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and ICU occupancy (P<0.05);obviously higher incidences of sepsis, shock, hypoproteinemia, respiratory failure, coagulation disorders, acute kidney injury, acute myocardial injury, acute respiratory distress syndrome (ARDS), and even mortality (P<0.05);and remarkably longer length of hospital stay (P<0.001) when compared with the normal calcium group. The blood calcium level of mild and common, severe, and critical COVID-19 patients was 2.17 (2.11, 2.24), 2.13 (2.04, 2.21), and 2.03 (1.89, 2.18) mmol/L, respectively, and significant differences were seen among the patients (P<0.05). The calcium level was in a decreasing trend with the severity of COVID-19 (P<0.05). The calcium level was statistically lower in the dead patients than those survival [1.97 (1.87, 2.03) vs 2.17 (2.09, 2.23), P<0.001]. Multivariate Cox regression analysis indicated that serum calcium concentration <2.11 mmol/L was an independent risk factor for poor prognosis of COVID-19 (HR=5.695, 95%CI :2.363-13.725, P<0.001). ConclusionLow blood calcium level is an independent risk factor for poor prognosis in COVID-19 patients. Correction for hypocalcemia may be an important strategy to improve the prognosis of COVID-19 patients.

Structure and function analysis of a potent human neutralizing antibody CA521FALA against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521FALA, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521FALA showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521FALA also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521FALA inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521FALA blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521FALA a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.

Sex Differences in the Incidence and Risk Factors of Myocardial Injury in COVID-19 Patients: A Retrospective Cohort Study.

Male novel coronavirus disease (COVID-19) patients tend to have poorer clinical outcomes than female patients, while the myocardial injury is strongly associated with COVID-19-related adverse events. Owing to a lack of corresponding data, we aimed to investigate the sex differences in the incidence of myocardial injury in COVID-19 patients and to identify the potential underlying mechanisms, which may partly account for the sex bias in the incidence of adverse events. This retrospective study included 1,157 COVID-19 patients who were hospitalized in Huoshenshan Hospital from 12 March 2020 to 11 April 2020. Data on the patients' demographic characteristics, initial symptoms, comorbidities and laboratory tests were collected. Totally, 571 (49.4%) female and 586 (50.6%) male COVID-19 patients were enrolled. The incidence of myocardial injury was higher among men than women (9.2 vs. 4.9%, p = 0.004). In the logistic regression analysis, age, and chronic kidney disease were associated with myocardial injury in both sexes. However, hypertension [odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.20-4.22], coronary artery disease (OR = 2.46, 95% CI 1.14-5.34), leucocyte counts (OR = 3.13, 95% CI 1.24-7.86), hs-CRP (OR = 4.45, 95% CI 1.33-14.83), and D-dimer [OR = 3.93 (1.27-12.19), 95% CI 1.27-12.19] were independent risk factors only in the men. The correlations of hs-CRP and D-dimer with hs-cTnI and BNP were stronger in the men. The incidence of myocardial injury in COVID-19 patients is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders in men. Our findings can be used to improve the quality of clinical management in such settings.

Influence of blood pressure control and application of renin-angiotensin-aldosterone system inhibitors on the outcomes in COVID-19 patients with hypertension.

Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID-19). However, little is known about the effects of pre-admission and/or in-hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in-hospital blood pressure (BP) control and COVID-19-related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID-19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13-0.97, P = .043) or after (HR = 0.18, 95%CI 0.04-0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID-19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01-0.83, P = .033) than non-RAAS inhibitors users. We revealed that COVID-19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID-19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID-19 patients with hypertension before and after admission.

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.

Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Anisodamine Hydrobromide Injection against Novel Coronavirus Pneumonia.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) outbreak in Wuhan, China, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anisodamine hydrobromide injection (AHI), the main ingredient of which is anisodamine, is a listed drug for improving microcirculation in China. Anisodamine can improve the condition of patients with COVID-19. MATERIALS AND METHODS: Protein-protein interactions obtained from the String databases were used to construct the protein interaction network (PIN) of AHI using Cytoscape. The crucial targets of AHI PIN were screened by calculating three topological parameters. Gene ontology and pathway enrichment analyses were performed. The intersection between the AHI component proteins and angiotensin-converting enzyme 2 (ACE2) coexpression proteins was analyzed. We further investigated our predictions of crucial targets by performing molecular docking studies with anisodamine. RESULTS: The PIN of AHI, including 172 nodes and 1454 interactions, was constructed. A total of 54 crucial targets were obtained based on topological feature calculations. The results of Gene Ontology showed that AHI could regulate cell death, cytokine-mediated signaling pathways, and immune system processes. KEGG disease pathways were mainly enriched in viral infections, cancer, and immune system diseases. Between AHI targets and ACE2 coexpression proteins, 26 common proteins were obtained. The results of molecular docking showed that anisodamine bound well to all the crucial targets. CONCLUSION: The network pharmacological strategy integrated molecular docking to explore the mechanism of action of AHI against COVID-19. It provides protein targets associated with COVID-19 that may be further tested as therapeutic targets of anisodamine.