Identification of immune cell infiltration and biomarkers in Alzheimer's disease and COVID-19 by integrated bioinformatics analysis and machine learning (preprint)

Background: Since its emergence in late 2019, COVID-19 has become a global epidemic, resulting in numerous infections, including a significant number of critically ill patients. Several studies have suggested a possible link between Alzheimer's disease (AD) and COVID-19. For instance, a Mendelian randomization study has proposed a causal relationship between Alzheimer's disease and COVID-19 in the pathogenic mechanism. However, there are limited studies exploring the common pathogenic genes and immune infiltration between the two. Therefore, we conducted this study to identify key genes in COVID-19 associated with Alzheimer's disease, evaluate their correlation with immune cell characteristics and metabolic pathways, and investigate potential novel biomarkers. Methods: Transcriptome analyses were used to identify common biomolecular markers of AD and COVID-19. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on gene chip datasets (GSE213313, GSE5281, and GSE63060) from AD and COVID-19 patients to identify genes associated with both conditions. Common pathogenic molecular mechanisms were identified through Gene Ontology (GO) enrichment analyses. The core genes were then identified using machine learning methods. Subsequently, we evaluated the relationship between these core genes and common immune cells and metabolic pathways. Finally, our findings were validated through single-cell analysis. Results: The study identified 484 common differentially expressed genes (DEGs) by taking the intersection of genes between AD and COVID-19. The black module, containing 132 genes, showed the highest association between the two diseases according to WGCNA. GO enrichment analysis revealed that these genes mainly affect inflammation, cytokines, immune-related functions, and signaling pathways related to metal ions and cellular response to viruses. Additionally, a machine learning approach identified eight core genes. We identified links between these genes and immune cells and also found a strong association between EIF3H and oxidative phosphorylation. In addition, these results were further validated by single-cell analysis. Conclusion: This study identifies potential shared genes, signaling pathways, immune-related alterations, and changes in metabolic pathways that may collectively contribute to the pathogenesis of COVID-19 and Alzheimer's disease. These findings provide new targets for the diagnosis and treatment of both diseases.

Effect of the COVID-19 on Patients with Systemic Lupus Erythematosus during the First Pandemic Wave in China (preprint)

Objective: This study aimed to investigate the prevalence and clinical manifestations of coronavirus disease (COVID-19) in patients with systemic lupus erythematosus (SLE) during the first wave of the pandemic in China and to evaluate the effects of COVID-19 on the disease activity and treatment of SLE.  Methods: A telephone survey was conducted on patients diagnosed with SLE in our hospital between October 2017 and October 2022. Through the survey, we investigated whether the patients had COVID-19, the clinical manifestations of the infection, whether the patients were vaccinated, the effects of the infection on the disease activity of SLE, and whether the treatment regimen for SLE was adjusted due to the infection.  Results: A total of 351 patients participated in this study, of whom 261 (74.4%) had COVID-19. Regarding organ involvement, the circulatory system was more commonly affected than the other organs in patients with SLE without COVID-19 (P = 0.002). Regarding concomitant medications, the daily dose of glucocorticoids was higher than that of other medication in SLE patients without COVID-19 (P = 0.000). No differences were observed in age, disease duration, disease activity, of other concomitant medications. While infected with COVID-19, 46 patients (17.6%) discontinued parts of their treatment without experiencing any episodes of SLE.  Conclusion: Most SLE patients with COVID-19 had a good prognosis, and all the patients in our study recovered from COVID-19 infection. Abrupt dose reduction and discontinuation of medications by the patients themselves may lead to elevated disease activity or even episodes of SLE. As such, it is recommended that the patients adjust their treatment regimens following the guidance of their specialists after careful evaluation of their condition and SLE disease activity by specialists.

Neural alterations of Omicron infection comorbid with insomnia in Chinese: Insight from surface-based morphometry and bibliometric analysis (preprint)

Growing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the central nervous system (CNS), and insomnia-related acute and long-term CNS sequelae may be suffered by infected patients. Nevertheless, as a common sub-typic strain of SARS-CoV-2, it is currently unknown the impacts of Omicron comorbid with insomnia on brain cortex. The purpose of this study was to mine the neural markers involving cortical grey matter volume (GMV), thickness, and surface area within Omicron individuals either with or without insomnia. Additionally, correlations between these morphological metrics and neuropsychiatric assessments were analyzed. 234 participants were recruited from a prospective cross-sectional study cohort during the Omicron pandemic (December 2022-May 2023) at the Second Xiangya Hospital (China). We further divided participants into healthy controls (HCs), Omicron infection with insomnia group (Omicron_insomnia group), and Omicron infection without insomnia group (Omicron_non_insomnia group). Based on T1-weighted MPRAGE image, cortical thickness, surface area, and GMV were compared via surface-based morphometry (SBM) analysis, and significant morphological metrics were then correlated with neuropsychiatric manifestations. Our findings revealed altered cortical morphology in Omicron individuals. Morphological changes in the temporal, frontal, cingulate, transverse collateral, and lingual gyrus were independent from insomnia comorbidity. The decreased cortical thickness in superior temporal gyrus (STG) was a specific feature for Omicron infection comorbid with insomnia. Then, we discovered greater morphological size indicating neuropsychiatric improvement. This study explores the neural mechanisms underlying Omicron infection comorbid with insomnia, which will help to promote improvement in post-Omicron neuropsychiatric prognosis and clinical management.

Safety and immunogenicity of a heterologous booster with an RBD virus-like particle vaccine following two- or three-dose inactivated COVID-19 vaccine (preprint)

Background: Reduced protection against COVID-19 due to the waning vaccine-induced immunity over time and emergence of immune-evading SARS-CoV-2 variants of concern (VOCs) indicate the need for vaccine boosters. LYB001 is an innovative recombinant SARS-CoV-2 vaccine which displays a repetitive array of the Spike glycoprotein's receptor binding domain (RBD) on a virus-like particle (VLP) vector to boost the immune system, produced using a Covalink plug-and-display protein binding technology. Methods: The safety and immunogenicity of LYB001 as a heterologous booster at an interval of 6-12 months was assessed in 119 participants receiving a booster with (1) 30g LYB001 (I-I-30L) or CoronaVac (I-I-C), (2) escalated dose of 60g LYB001 (I-I-60L) or CoronaVac in a ratio of 2:1 after two-dose primary series of inactivated COVID-19 vaccine in part 1 of this study, or (3) 30g LYB001 (I-I-I-30L) after three-dose primary series of inactivated COVID-19 vaccine in part 2 of this study. Results: A well-tolerated reactogenicity profile was observed for LYB001 as a heterologous booster, with adverse reactions predominantly being mild in severity and transient. The peak neutralizing antibody response was observed at 28 days after booster, with GMT (95%CI) against prototype SARS-CoV-2 being 1237.8 (747.2, 2050.6), 554.3 (374.6, 820.2), 181.9 (107.6, 307.6) and 1200.2 (831.5, 1732.3) in the I-I-30L, I-I-60L, I-I-C, and I-I-I-30L groups, respectively. LYB001 also elicited a cross-neutralizing antibody response against the BA.4/5 strain, dominant during the study period, with GMT being 201.1 (102.7, 393.7), 63.0 (35.1, 113.1), 29.2 (16.9, 50.3) and 115.3 (63.9, 208.1) at 28 days after booster in the I-I-30L, I-I-60L, I-I-C, and I-I-I-30L groups, respectively. Additionally, RBD-specific IFN-{gamma}, IL-2, IL-4 secreting T cells, as measured by ELISpot assay, dramatically increased (more than 10 times versus baseline) at 14 days after a single LYB001 booster. Conclusions: Our data confirm the favorable safety and immunogenicity profile of the LYB001 vaccine when used as a heterologous booster, and support the continued clinical development of this promising candidate that utilize VLP platform to provide protection against COVID-19.

Mediating Role of Anxiety and Depression in Relationship between Coping Style and Life Satisfaction in Medical Workers during COVID-19 Pandemic in China (preprint)

Objective: This study aimed to examine the mediating role of anxiety and depression on the relationship between coping styles and life satisfaction in medical workers during the COVID-19 pandemic. Methods：Five hundred and fourteen frontline medical workers from Zunyi were recruited to complete questionnaires, including the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Satisfaction With Life Scale (SWLS), and Simplified Coping Style Questionnaire (SCSQ). Results：The results revealed the following: a) The prevalence of anxiety was 22.57%, and the prevalence of depression was 18.29%. b) Anxiety was positively correlated with depression; anxiety and depression were positively correlated with passive coping styles but negatively correlated with life satisfaction and active coping styles; life satisfaction was positively correlated with active coping styles and negatively correlated with passive coping styles. c) Anxiety and depression partially mediated the relationship between active coping styles and life satisfaction. Conclusion：Some frontline medical workers in the pandemic area had subclinical anxiety and depression, and anxiety and depression had a mediating effect on the relationship between coping styles and life satisfaction.

Potato Processing Industry in China: Current Scenario, Future Trends and Global Impact

  Potatoes play an important role in ensuring food security. During the COVID-19 epidemic, consumption of processed potato products decreased, and consumption of fresh potatoes increased. China is the world’s largest potato producer with more than 4.81 million hectares of area under potato production and 90.32 million metric tonnes of potatoes produced in 2018. This accounts for 27.36% of the world’s planting area and 24.53% of the world’s potato production. The proportion of potatoes processed in China was about 12% in 2017, mostly dominated by starch production. However, the recent policy of the Chinese government to popularise potato as a staple food has created new markets for processed potato products other than starch. A very few reports have analysed these future trends of the rapidly growing Chinese potato processing industry and its impact within and outside China. This paper provides an overview of the latest developments with a focus on processed potato products such as potato chips, French fries and dehydrated potatoes, and also, due to the unique Chinese diet culture, it highlights the need for more scientific research dedicated towards the development of novel potato-based healthy foods.

Advances in the application of CRISPR-Cas system for SARS-CoV-2 diagnostic test

The outbreak of coronavirus disease 2019（COVID-19）, caused by severe acute respiratory syndrome coronavirus（SARS-CoV-2） at the end of 2019, results in a global rapid pandemic.The emerging infectious disease is life threaten and profoundly undermines the normal operation all over the world.Rapid and accurate detection of SARS-CoV-2 is an essential component of efforts to combat SARS-CoV-2 spread.Although many technologies for SARS-CoV-2 detection have been commercialized and have played a role in the control of COVID-19 epidemic to some extent yet, each of them is still with certain limitations.Recently, increasing number of teams attempt to detect SARS-CoV-2 by CRISPR-Cas（clustered regularly interspaced short palindromic repeats-Cas） system.With excellent specificity and sensitivity, it has been believed to be a potential technology in COVID-19 diagnosis and therapy.The review provides an overview of CRISPR-Cas system for SARS-CoV-2 detection and COVID-19 therapy, along with its clinical translation potential.Hope it has some referential significance for the control of SARS-CoV-2 spread and COVID-19 epidemic.

Optimal metabolic states in cells (preprint)

Cells, in order to thrive, make efficient use of metabolites, proteins, energy, membrane space, and time. How, for example, should they allocate the available amount of protein to different metabolic pathways or cell functions? To model metabolic behaviour as an economic problem, some flux analysis model, kinetic models, and cell models apply optimality principles. However, due to their different assumptions these models are hard to compare and combine. Benefits and costs of metabolic pathways - e.g. favouring high production fluxes and low metabolite and enzyme cost - can be derived from general fitness objectives such as fast cell growth. To define pathway objectives, we may assume "optimistically" that, given a pathway state, any cell variables outside the pathway will be chosen for maximal fitness. The resulting fitness defines an effective pathway objective as a function of the pathway variables. Here I propose a unified theory that considers kinetic models, describes the set of feasible states as a state manifold and score each state by cost and benefit functions for fluxes, metabolite concentrations, and enzyme levels. To screen the state manifold and to find optimal states, the problem can be projected into flux, metabolite, or enzyme space, where effective cost and benefit functions are used. We reobtain existing modelling approaches such as enzyme cost minimisation or nonlinear versions of Flux Balance Analysis. Due to their common origin, the different approaches share mathematical optimality conditions of the same form. A general theory of optimal metabolic states, as proposed here, provides a logical link between existing modelling approaches and can help justify, interconvert, and combine metabolic optimality problems.

Clinical Characteristics of Omicron SARS-CoV-2 Variant Infection After Non-mRNA-Based Vaccination in China

Introduction To date, little is known about the real-world protective role of Chinese inactivated and recombinant coronavirus disease 2019 (COVID-19) vaccines under the background of the long-term “Dynamic Zero COVID-19 Case” (i.e., no infection source) in China, especially when facing the widespread Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection. Methods In this prospective, single-center cohort study, the clinical characteristics of post-vaccination Omicron SARS-CoV-2 variant infection were investigated in the initial largest outbreak of Omicron SARS-CoV-2 variant infection that occurred between the 8 January, 2022 and 29 January, 2022 in Anyang City, Henan Province, China. The primary endpoints were the rates of severe and critical diseases or death. The secondary endpoints were the SARS-CoV-2 shedding duration and length of hospitalization. Results A total of 380 post-vaccination patients infected with the Omicron SARS-CoV-2 variant were enrolled. The median age was 18 (interquartile range [IQR] 17–35) years, 219 (57.6%) cases were female, and 247 (65.0%) cases were students. Before confirmation of Omicron SARS-CoV-2 variant infection, patients had 3 (IQR 2–4) days of dry cough (40.3%), nasal congestion (26.3%), and sore throat (26.3%). On admission, 294 (77.4%) cases had normal chest computerized tomography (CT) imaging. Additionally, only 5 (1.3%), 30 (7.9%), 4 (4/342, 1.2%), and 7 (7/379, 0.2%) patients had lymphocyte counts <800 per mm3, C-reactive protein levels >10 mg/L, lactate dehydrogenase levels ≥250 U/L, and D-dimer levels ≥0.5 mg/L on admission, respectively. During hospitalization, 308 (81.1%) and 72 (18.9%) were identified as mild and moderate cases, respectively, and no one progressed to severe and critical types, with a SARS-CoV-2 shedding period and length of hospital stay of 17 (IQR 12–22) and 19 (IQR 15–24) days, respectively. Conclusion The current study found that approximately 80% of individuals infected with the Omicron SARS-CoV-2 variant were mild, approximately 20% of patients were moderate, and no severe, critical, or fatal cases were identified in a prospective cohort including 380 participants vaccinated with non-mRNA-based vaccines. Discussion This study supports the consideration of policy adjustments and changes to prevent and control the Omicron-predominant COVID-19 in China and other regions with high SARS-CoV-2 vaccination rates.

Clinical Characteristics of Immune Response in Asymptomatic Carriers and Symptomatic Patients With COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.

Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-Cov-2 and Variants (preprint)

The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here we developed covalent nanobodies capable of binding with SARS-CoV-2 spike protein irreversibly via proximity-enabled reactive therapeutic (PERx) mechanism. A novel latent bioreactive amino acid FFY was designed and genetically encoded into nanobodies to accelerate PERx reaction rate. After covalent engineering, nanobodies binding with the Spike in the down state, but not in the up state, were discovered to possess striking enhancement in inhibiting viral infection. In comparison with the noncovalent wildtype nanobody, the FFY-incorporated covalent nanobody neutralized both authentic SARS-CoV-2 and its Alpha and Delta variants with potency drastically increased over tens of folds. This PERx-enabled covalent nanobody strategy and uncovered insights on potency increase can be valuable to developing effective therapeutics for various viral infections.

Determinants of Telemedicine Adoption among Financially Distressed Patients with Cancer During the COVID-19 Pandemic: Insights from a Nationwide Survey (preprint)

Purpose: Telemedicine use during the COVID-19 pandemic among financially distressed patients with cancer, with respect to the determinants of adoption and patterns of utilization, has yet to be delineated. We sought to systematically characterize telemedicine utilization in financially distressed patients with cancer during the COVID-19 pandemic.Methods: We conducted a cross-sectional analysis of nationwide survey data assessing telemedicine use in patients with cancer during the COVID-19 pandemic collected by Patient Advocate Foundation (PAF) in December 2020. Primary study outcome was telemedicine utilization during the pandemic. Secondary outcomes were telemedicine utilization volume and modality preferences. Multivariable and Poisson regression analyses were used to identify factors associated with telemedicine use.Results: A convenience sample of 627 patients with cancer responded to the PAF survey. Telemedicine adoption during the pandemic was reported by 67% of patients, with most (63%) preferring video visits. Younger age (19-35 age compared to ≥ 75 age) (OR, 6.07; 95% CI, 1.47-25.1), and more comorbidities (≥ 3 comorbidities compared to cancer only) (OR, 1.79; 95% CI, 1.13-2.65) were factors associated with telemedicine adoption. Younger age (19-35 yrs.) (incidence rate ratios [IRR], 1.78; 95%CI, 24-115%) and higher comorbidities (≥3) (IRR; 1.36; 95%CI, 20-55%) were factors associated with higher utilization volume. As area deprivation index increased by 10 units, the number of visits decreased by 3% (IRR 1.03, 95%CI, 1.03-1.05).Conclusions: The rapid adoption of telemedicine may exacerbate existing inequities, particularly among vulnerable financially financially-distressed patients with cancer. Policy-level interventions are needed for the equitable and efficient provision of this service. 

The Moral Injury, PTSD, and Suicidal Behaviors in Health Professionals 1 Year After the COVID-19 Pandemic Peak in China (preprint)

Background: Moral injury among healthcare workers received considerable attention in China during the COVID-19 pandemic as a predictor of poor mental health outcomes. This study explored the relationship between moral injury, PTSD, and suicidal behaviors approximately 1 year after the pandemic peaked in this country. Methods An online survey was conducted from March 27 to April 26, 2021, across mainland China. A total of 3,465 health professionals completed the Chinese version of the Moral Injury Symptoms Scale-Health Professional (MISS-HP), Suicidal Behaviors Questionnaire-Revised (SBQ-R), and PTSD Checklist for DSM-5 (PCL‐5). Unconditional logistic regression modeling was used to examine the association between these variables. Results The prevalence of PTSD and suicidal behavior among health professionals were 26.9% and 24.2%, respectively. The MISS-HP was positively correlated with PCL-5 (r = 0.43) and SBQ-R (r = 0.24) scores. Logistic regression revealed that MI was associated with a higher likelihood of PTSD (OR = 3.52, 95% CI: 3.01–4.13) and of suicidal behaviors (OR = 2.13, 95% CI:1.81–2.50) after controlling for socio-demographical variables. Conclusions Moral injury symptoms were associated with a higher risk of PTSD and more suicidal behaviors among health professionals 1 year after the peak of the COVID-19 pandemic. The findings underscore the importance of identifying and treating the moral injury as one way to manage PTSD and suicidal behaviors among health professionals during the post-pandemic period.

ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells (preprint)

Currently, the COVID-19 pandemic, caused by SARS-CoV-2 infection, represents a serious public health problem worldwide. Although it has been shown that ACE2 serves as the main receptor for SARS-CoV-2 entry into host cells, studies have shown that ACE2 is expressed at extremely low levels in various tissues, especially in some organs where virus particles have been found, such as the heart and liver. Therefore, these organs potentially express additional SARS-CoV-2 receptors that have not yet been discovered. Here, by a genome-wide CRISPR-Cas9 activation library screening, we found that ASGR1 promoted SARS-CoV-2 infection of 293T cells. In Huh-7 and HepG2 cell lines, simultaneous knock out of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary liver parenchymal cells, both of which hardly express ACE2, SARS-CoV-2 could successfully establish an infection. After treatment with ASGR1 antibody, the infection rate significantly reduced. This suggests that SARS-CoV-2 infects liver cells mainly through an ASGR1-dependent mechanism. Finally, we also found that the soluble ASGR1 could not only prevent the SARS-CoV-2 pseudovirus, which binds to the ASGR1 receptors, from infecting host liver cells, but also had a protective effect on those expressing ACE2, indicating that administration of soluble ASGR1 protein may represent a new treatment approach. CONCLUSIONS: Colletively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells.

Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies (preprint)

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.