Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Genetic screening for hypertension and COVID-19 reveals functional variation of SPEG potentially associated with severe COVID-19 in women.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women.

Ocular inflammatory manifestations following COVID-19 vaccinations in Taiwan: A case series.

As a continuing demand for booster shots against SARS-CoV-2, ocular adverse events following the coronavirus disease-2019 (COVID-19) vaccines can cause significant visual impairment, and they warrant a high awareness and detailed documentation of possible ocular inflammatory manifestations. We present a case series of 11 patients presenting with ocular manifestations relevant to vaccine-associated autoimmune response within 6 weeks after the vaccination of the Oxford-AstraZeneca, the Moderna, and Pfizer-BioNTech vaccines at the main tertiary referral center in the most populated and most vaccinated city in Taiwan. Their diagnosis included five acute anterior uveitis, two multiple evanescent white dot syndrome, one probable Vogt-Koyanagi-Harada disease, one anterior scleritis, one relapsed idiopathic panuveitis, and one autoantibody-related central retinal artery occlusion. This report presented a broad spectrum of the ocular inflammatory events following the vaccination of COVID-19. Early recognition of the clinical manifestations mentioned herein with prompt management is crucial in recovering the patients' vision.

The derived neutrophil to lymphocyte ratio can be the predictor of prognosis for COVID-19 Omicron BA.2 infected patients.

Background: Several systemic inflammatory biomarkers have been associated with poor overall survival (OS) and disease severity in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear which markers are better for predicting prognosis, especially for COVID-19 Omicron BA.2 infected patients. The present study aimed to identify reliable predictors of prognosis of COVID-19 Omicron BA.2 from inflammatory indicators. Methods: A cohort of 2645 COVID-19 Omicron BA.2 infected patients were retrospectively analyzed during the Omicron BA.2 surge in Shanghai between April 12, 2022, and June 17, 2022. The patients were admitted to the Shanghai Fourth People's Hospital, School of Medicine, Tongji University. Six systemic inflammatory indicators were included, and their cut-off points were calculated using maximally selected rank statistics. The analysis involved Kaplan-Meier curves, univariate and multivariate Cox proportional hazard models, and time-dependent receiver operating characteristic curves (time-ROC) for OS-associated inflammatory indicators. Results: A total of 2347 COVID-19 Omicron BA.2 infected patients were included. All selected indicators proved to be independent predictors of OS in the multivariate analysis (all P < 0.01). A high derived neutrophil to lymphocyte ratio (dNLR) was associated with a higher mortality risk of COVID-19 [hazard ratio, 4.272; 95% confidence interval (CI), 2.417-7.552]. The analyses of time-AUC and C-index showed that the dNLR (C-index: 0.844, 0.824, and 0.718 for the 5th, 10th, and 15th day, respectively) had the best predictive power for OS in COVID-19 Omicron BA.2 infected patients. Among different sub-groups, the dNLR was the best predictor for OS regardless of age (0.811 for patients aged ≥70 years), gender (C-index, 0.880 for men and 0.793 for women) and disease severity (C-index, 0.932 for non-severe patients and 0.658 for severe patients). However, the platelet to lymphocyte ratio was superior to the other indicators in patients aged <70 years. Conclusions: The prognostic ability of the dNLR was higher than the other evaluated inflammatory indicators for all COVID-19 Omicron BA.2 infected patients.

Satellite-based estimates of daily NO2 exposure in urban agglomerations of China and application to spatio-temporal characteristics of hotspots

The analysis of the daily spatial patterns of near-surface Nitrogen dioxide (NO2) concentrations can assist decision makers mitigate this common air pollutant in urban areas. However, comparative analysis of NO2 estimates in different urban agglomerations of China is limited. In this study, a new linear mixed effect model (LME) with multi-source spatiotemporal data is proposed to estimate daily NO2 concentrations at high accuracy based on the land-use regression (LUR) model and Ozone Monitoring Instrument (OMI) and TROPOspheric Monitoring Instrument (TROPOMI) products. In addition, three models for NO2 concentration estimation were evaluated and compared in four Chinese urban agglomerations from 2018 to 2020, including the COVID-19 closed management period. Each model included a unique combination of methods and satellite NO2 products: ModelⅠ: LUR model with OMI products;Model Ⅱ: LUR model with TropOMI products;Model Ⅱ: LME model with TropOMI products. The results show that the LME model outperformed the LUR model in all four urban agglomerations as the average RMSE decreased by 16.09% due to the consideration of atmospheric dispersion random effects, and using TropOMI instead of OMI products can improve the accuracy. Based on our NO2 estimations, pollution hotspots were identified, and pollution anomalies during the COVID-19 period were explored for two periods;the lockdown and revenge pollution periods. The largest NO2 pollution difference between the hotspot and non-hotspot areas occurred in the second period, especially in the heavy industrial urban agglomerations.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1-2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Changes of ACE2 in different glucose metabolites and its relationship with COVID-19.

BACKGROUND: To study the changes and effects of angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang1-7) and ACE/AngII in people with different glucose metabolisms and to explore the possible mechanisms underlying the severity of COVID-19 infection in diabetic patients. METHODS: A total of 88 patients with type 2 diabetes, 72 patients with prediabetes (impaired fasting glucose, 30 patients; impaired glucose regulation, 42 patients), and 50 controls were selected. Changes and correlations of ACE2, Ang1-7 and other indicators were detected among the three groups. Patients were divided into four groups according to the course of diabetes: <1 year, 1-5 years, 5-10 years, and >10 years. ACE2 and Ang1-7 levels were compared and analyzed. RESULTS: ACE2 and Ang1-7 increased with the severity of diabetes (P0 < .05 or P < .01). The levels of ACE2 and Ang1-7 in the longer course group were lower than those in the shorter course group, whereas the levels of ACE, Ang II, and interleukin-6 (IL-6) gradually increased (P < .05). Pearson correlation analysis showed that ACE2 was positively correlated with IL-6, FBG, and 2hPBG levels in the prediabetes group. In the diabetic group, ACE2 was positively correlated with Ang1-7 and negatively correlated with ACE, AngII, IL-6, and C-reactive protein levels. Multiple linear regression analysis showed that IL-6 and ACE were the main factors influencing ACE2 in the diabetic group. CONCLUSION SUBSECTIONS: ACE2/Ang1-7 and ACE/AngII systems are activated, and inflammatory cytokine release increases in prediabetes. With the prolongation of the disease course, the effect of ACE2/Ang1-7 decreased gradually, while the effect of ACE/AngII increased significantly. Dysfunctions of ACE2/Ang1-7 may be one of the important mechanisms underlying the severity of COVID-19 infection in patients with diabetes.

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

A Houttuynia cordata-based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic.

BACKGROUND: The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic. METHODS: Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated. RESULTS: Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model. CONCLUSION: ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.

A fast online questionnaire for screening mental illness symptoms during the COVID-19 pandemic.

The COVID-19 pandemic has caused massive effects on the situation of public mental health. A fast online questionnaire for screening and evaluating mental symptoms is urgent. In this work, we developed a new 19-item self-assessment Fast Screen Questionnaire for Mental Illness Symptoms (FSQ-MIS) to quickly identify mental illness symptoms. The FSQ-MIS was validated on a total of 3828 young adult mental disorder patients and 984 healthy controls. We applied principal component analysis (PCA), receiver operating characteristic (ROC) curve, and general log-linear analysis (GLA) to evaluate the construct and parallel validity. Results demonstrate that the proposed FSQ-MIS shows high test-retest reliability (0.852) and split-half reliability (0.844). Six factors obtained using PCA explained 54.3% of the variance and showed high correlations with other widely used scales. The ROC results (0.716-0.983) revealed high criterion validity of FSQ-MIS. GLA demonstrated the advantage of FSQ-MIS in predicting anxiety and depression prevalence in COVID-19, supporting the efficiency of FSQ-MIS as a tool for research and clinical practice.

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as “brain fog”, which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

Endothelial Biomarkers in Patients Recovered from COVID-19 One Year after Hospital Discharge: A Cross-Sectional Study.

Background: COVID-19 is characterized by endothelial dysfunction and is presumed to have long-term cardiovascular sequelae. In this cross-sectional study, we aimed to explore the serum levels of endothelial biomarkers in patients who recovered from COVID-19 one year after hospital discharge. Methods: In this clinical follow-up study, 345 COVID-19 survivors from Huanggang, Hubei, and 119 age and gender-matched medical staff as healthy controls were enrolled. A standardized symptom questionnaire was performed, while electrocardiogram and Doppler ultrasound of lower extremities, routine blood tests, biochemical and immunological tests, serum soluble vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), P-selectin, and fractalkine were measured by enzyme-linked immunosorbent assays (ELISA). Results: At one year after discharge, 39% of recovers possessed post-COVID syndromes, while a few had abnormal electrocardiogram manifestations, and no deep vein thrombosis was detected in all screened survivors. There were no significant differences in circulatory inflammatory markers (leukocytes, neutrophils, lymphocytes, C-reactive protein and interleukin-6), alanine aminotransferase, estimated glomerular filtration rate, glucose, triglycerides, total cholesterol and D-dimer observed among healthy controls with previously mild or severe infected. Furthermore, serum levels of VCAM-1, ICAM-1, P-selectin, and fractalkine do not significantly differ between survivors and healthy controls. Conclusions: SARS-CoV-2 infection may not impose a higher risk of developing long-term cardiovascular events, even for those recovering from severe illness.

Electrochemical biosensors for the detection of SARS-CoV-2 pathogen and protein biomarkers.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV CoV-2) pathogen and protein biomarkers can improve the diagnosis accuracy for Coronavirus disease 2019 (COVID-19). Electrochemical biosensors have attracted extensive attention in the scientific community because of their simple design, fast response, good portability, high sensitivity and high selectivity. In this review, we summarized the progress in the electrochemical detection of COVID-19 pathogen and SARS-CoV-2 biomarkers, including SARS-CoV-2 spike protein and nucleocapsid protein and their antibodies.

Global Identification of Unelectrified Built-Up Areas by Remote Sensing

Access to electricity (the proportion of the population with access to electricity) is a key indica for of the United Nations’ Sustainable Development Goal 7 (SDG7), which aims to provide affordable, reliable, sustainable, and modern energy services for all. Accurate and timely global data on access to electricity in all countries is important for the achievement of SDG7. Current survey-based access to electricity datasets suffers from short time spans, slow updates, high acquisition costs, and a lack of location data. Accordingly, a new method for identifying the electrification status of built-up areas based on the remote sensing of nighttime light is proposed in this study. More specifically, the method overlays global built-up area data with night-time light remote sensing data to determine whether built-up areas are electrified based on a threshold night-time light value. By using our approach, electrified and unelectrified built-up areas were extracted at 500 m resolution on a global scale for the years 2014 and 2020. The acquired results show a significant reduction in an unelectrified built-up area between 2014 and 2020, from 51,301.14 km2 to 22,192.52 km2, or from 3.05% to 1.32% of the total built-up area. Compared to 2014, 117 countries or territories had improved access to electricity, and 18 increased their proportion of unelectrified built-up area by >0.1%. The identification accuracy was evaluated by using a random sample of 10,106 points. The accuracies in 2014 and 2020 were 97.29% and 98.9%, respectively, with an average of 98.1%. The outcomes of this method are in high agreement with the spatial distribution of access to electricity data reported by the World Bank. This study is the first to investigate the global electrification of built-up areas by using remote sensing. It makes an important supplement to global data on access to electricity, which can aid in the achievement of SDG7.

Different impacts of cancer types on cancer screening during COVID-19 pandemic in Taiwan.

BACKGROUND: The COVID-19 pandemic has rapidly become a major challenge for global health care systems and affected other priorities such as the utilization of population-based cancer screening services. We sought to examine to what extent the COVID-19 pandemic has affected cancer screening utilization in Taiwan, even the use of inreach and outreach screening services for different types of cancer screening and different regions. METHODS: Using nationwide cervical, breast, colorectal and oral cancer screening data, the percentage changes in screening participants at inreach and outreach services were calculated and compared between January to April 2020 (COVID-19 pandemic) and January to April 2019. RESULTS: The average percentage change declined from 15% to 40% for cervical, breast, and colorectal cancer screening, with a nearly 50% decline in oral cancer screening. There was a greater preference for breast and colorectal cancer screening outreach services, which had greater accessibility and declined less than inreach services in most regions. The screening utilization varied in different regions, especially in eastern Taiwan where the less convenient transportation and lower risk of COVID-19 transmission had a positive change on four types of cancer screening outreach services. CONCLUSION: The COVID-19 pandemic may have had an effect not only in the utilization of different types of cancer screening but also in the preference between inreach and outreach services, and even in variations in screening services in different regions.

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.