Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Moxibustion Treatment of COVID-19 and Rehabilitation Period of COVID-19: A Scoping Review.

Objective: The aim of this study is to provide a scoping review of the clinical literature on moxibustion therapy for the treatment of Coronavirus disease 2019 (COVID-19). Design: The PubMed, Embase, Cochrane Library, MEDLINE, CNKI, Wanfang, and VIP databases were searched from January 1, 2020, to August 31, 2022. Essential data were extracted from each article, and the data were displayed using tables and graphs. The study did not require IRB approval. Results: This scoping review included 14 research articles: 8 observational studies, 5 randomized controlled trials, and 1 nonrandomized clinical trial. All the studies were published by Chinese scholars. The findings revealed that moxibustion can contribute to reducing the symptoms of patients with COVID-19, improving inflammation and immune indicators, and shortening the time of nucleic acid negative conversion. Moxibustion confers curative effects on patients of all ages and degrees of illness. In addition, moxibustion can optimize the prognosis of patients in the rehabilitation period. The most commonly chosen acupoints are ST36, RN4, RN8, and RN12. No side effect was mentioned in the included studies. Conclusion: Moxibustion can produce a good effect in the treatment and rehabilitation of patients with COVID-19. It is safe, effective, simple, and noninvasive and should be included as standard care.

Differences in posttraumatic stress disorder networks between young adults and adolescents during the COVID-19 pandemic.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been frequently reported during the COVID-19 pandemic. Although there is evidence for age differences in PTSD symptoms, many studies assume that PTSD is a latent entity and overlook such differences. To address this gap, the aim of this study was to use network analysis to examine and compare PTSD symptom networks across different ages. METHOD: During the COVID-19 pandemic, 1,153 young adults and 683 adolescents were selected to complete self-report questionnaires. RESULTS: Two networks shared core symptoms (e.g., exaggerated startle response and irritability) in the arousal cluster. A network comparison test indicated that the young adult network was significantly stronger than the adolescent network. Except for exaggerated startle response and lack of positive emotion, symptoms in the young adult network exhibited higher centrality than in the adolescent network. CONCLUSIONS: An age difference in PTSD at the symptom level and provide practical evidence that could inform mental health interventions after the COVID-19 pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cellular mechanisms and clinical applications for phenocopies of inborn errors of immunity: infectious susceptibility due to cytokine autoantibodies.

INTRODUCTION: With a growing knowledge of Inborn errors immunity (IEI), immunological profiling and genetic predisposition to IEI phenocopies have been developed in recent years. AREAS COVERED: Here we summarized the correlation between various pathogen invasions, autoantibody profiles, and corresponding clinical features in the context of patients with IEI phenocopies. It has been extensively evident that patients with anti-cytokine autoantibodies underly impaired anti-pathogen immune responses and lead to broad unregulated inflammation and tissue damage. Several hypotheses of anti-cytokine autoantibodies production are summarized here, including a defective negative selection of autoreactive T cells, abnormal germinal center formation, molecular mimicry, HLA class II allele region, lack of auto-reactive lymphocyte apoptosis, and other possible hypotheses. EXPERT OPINION: Phenocopies of IEI associated with anti-cytokine autoantibodies are increasingly recognized as one of the causes of acquired immunodeficiency and susceptibility to certain pathogen infections, especially facing the current challenge of the COVID-19 pandemic. By investigating clinical, genetic, and pathogenesis autoantibodies profiles associated with various pathogens' susceptibilities, we could better understand the IEI phenocopies with anti-cytokine autoantibodies, especially for those that underlie life-threatening SARS-CoV-2.

19n01, a broadly neutralizing antibody against omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern.

This study reports the isolation and characterization of a human monoclonal antibody (mAb) called 19n01. This mAb was isolated by using single-cell RNAseq of B cells from donors infected with the ancestral strain. This mAb possesses a potent and broad capacity to bind and neutralize all previously circulating variants of concern (VOCs), including Omicron sublineages BA.1, BA.2, and BA.4/5. The pseudovirus neutralization assay revealed robust neutralization capacity against the G614 strain, BA.1, BA.2, and BA.4/5, with inhibitory concentration (IC50) values ranging from 0.0035 to 0.0164 µg/mL. The microneutralization assay using the G614 strain and VOCs demonstrated IC50 values of 0.013-0.267 µg/mL. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the receptor-binding domain (RBD) and the kinetic parameters confirmed the high affinity against the Omicron sublineages (KD of 61 and 30 nM for BA.2 and BA.4/5, respectively). These results suggest that the 19n01 is a remarkably potent and broadly reactive mAb.

19n01, a broadly neutralizing antibody against Omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern

This study reports the isolation and characterization of a human monoclonal antibody (mAb) called 19n01. This mAb was isolated by using single-cell RNAseq of B cells from donors infected with the ancestral strain. This mAb possesses a potent and broad capacity to bind and neutralize all previously circulating variants of concern (VOCs), including Omicron sublineages BA.1, BA.2, and BA.4/5. The pseudovirus neutralization assay revealed robust neutralization capacity against the G614 strain, BA.1, BA.2, and BA.4/5, with IC50 values ranging from 0.0035 to 0.0164 μg/mL. The microneutralization assay using the G614 strain and VOCs demonstrated IC50 values of 0.013 to 0.267 μg/mL. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the RBD and the kinetic parameters confirmed the high affinity against the Omicron sublineages (KD of 61 and 30 nM for BA.2 and BA.4/5, respectively). These results suggest that the 19n01 is a remarkably potent and broadly reactive mAb. Graphical

Digital Barriers and Individual Coping Behaviors in Distance Education During COVID-19

Information and communication technologies (ICT) have played a pivotal role in facilitating knowledge acquisition and enabling distance education. Yet, knowledge about digital divide in distance education remains limited. This study examines digital barriers that underserved students face in distance education and their coping behaviors during the coronavirus pandemic (COVID-19). Informed by distance education and digital divide literature, this study uses qualitative research method to analyze survey data collected from 206 college students in a four-year public university in the United States. Results revealed five major digital barriers and showed that the distribution of these digital barriers varied by student demographic background and socioeconomic status. Further analysis of respondents' narratives revealed three coping behaviors, including improvising, building technical assets, and building social assets. Practical implications are provided to educators and policymakers to invest in ICT and implement equity-minded teaching practices to enhance digital inclusion. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Positive Matrix Factorization as Source Apportionment of Paddy Soil Heavy Metals in Black Shale Areas in Western Zhejiang Province, China

The source apportionment of pollutants is the key to preventing and controlling the pollution caused by heavy metals in soils. The aim of this study was to investigate the main sources of heavy metals in the soils of black shale areas in western Zhejiang, China. Based on geostatistical spatial analysis, this research employed positive matrix factorization (PMF) for the source apportionment of heavy metals in paddy soil. The results showed that contaminated arable soils were concentrated in the western and southern study areas. At least five major sources of heavy metals were screened in this study: natural sources (39.66%), traffic emissions (32.85%), industrial emissions (9.23%), agricultural activities (9.17%), and mining (9.10%). To be specific, Cd was mainly from mining;As originated from agricultural inputs such as fertilizers and pesticides;and Hg, as an industrial pollutant, was transported by atmospheric deposition in the study area. The accumulation of Pb, Zn, and Cu was mainly influenced by natural sources and anthropogenic sources, i.e., traffic emissions, while that of Cr and Ni was controlled by natural sources.

Longitudinal proteomic investigation of COVID-19 vaccination.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Causal Inference of Central Nervous System-Regulated Hormones in COVID-19: A Bidirectional Two-Sample Mendelian Randomization Study.

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies of the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. DHEA was associated with increased risks of very severe respiratory syndrome (odds ratio [OR] = 4.21, 95% confidence interval [CI]: 1.41-12.59), consistent with multivariate MR results (OR = 3.72, 95% CI: 1.20-11.51), and hospitalization (OR = 2.31, 95% CI: 1.13-4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR = 0.83; 95% CI: 0.71-0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR = 0.09, 95% CI: 0.02-0.51), hospitalization (OR = 0.25, 95% CI: 0.08-0.78), and susceptibility (OR = 0.50, 95% CI: 0.28-0.89) in multivariate MR. We found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes.

Intervention uncertainty, household health, and pandemic.

This study builds a policy choice model wherein household health status responds to the lockdown during the COVID-19 pandemic. Considering an exogenous policy-decision date, the model implies that the government should maintain the current policy if the perceived effects on infection are below a certain threshold. Specifically, the threshold is determined by policy uncertainty and household concerns regarding health service provision, which further controls the announcement effects of the lockdown. Higher policy uncertainty and concerns regarding health services will diminish the positive impact of the lockdown on household health status.

Intervention uncertainty, household health, and pandemic☆

This study builds a policy choice model wherein household health status responds to the lockdown during the COVID-19 pandemic. Considering an exogenous policy-decision date, the model implies that the government should maintain the current policy if the perceived effects on infection are below a certain threshold. Specifically, the threshold is determined by policy uncertainty and household concerns regarding health service provision, which further controls the announcement effects of the lockdown. Higher policy uncertainty and concerns regarding health services will diminish the positive impact of the lockdown on household health status.

Synergism of TNF-α and IFN-ß triggers human airway epithelial cells death by apoptosis and pyroptosis.

Cytokine release syndrome, also called cytokine storm, could cause lung tissue damage, acute respiratory distress syndrome (ARDS) and even death during SARS-CoV-2 infection. However, the underlying mechanisms of cytokine storm still remain unknown. Among these cytokines, the function of TNF-α and type I IFNs especially deserved further investigation. Here, we first found that TNF-α and IFN-ß synergistically induced human airway epithelial cells BEAS-2B death. Mechanistically, the combination of TNF-α and IFN-ß led to the activation of caspase-8 and caspase-3, which initiated BEAS-2B apoptosis. The activated caspase-8 and caspase-3 could further induce the cleavage and activation of gasdermin D (GSDMD) and gasdermin E (GSDME), which finally resulted in pro-inflammatory pyroptosis. The knock-down of caspase-8 and caspase-3 could effectively block the activation of GSDMD and GSDME, and then the death of BEAS-2B induced by TNF-α and IFN-ß. In addition, pan-caspase inhibitor Z-VAD-FMK (ZVAD) and necrosulfonamide (NSA) could inhibit BEAS-2B death induced by TNF-α and IFN-ß. Overall, our work revealed one possible mechanism that cytokine storm causes airway epithelial cells (AECs) damage and ARDS. These results indicated that blocking TNF-α and IFN-ß-mediated AECs death may be a potential target to treat related viral infectious diseases, such as COVID-19.

Temporal and Spatial Cluster Analysis of 2019 Novel Coronavirus Pneumonia in Chongqing, 2020.1∼2020.2.

In order to explore the spatial and temporal distribution characteristics of COVID-19 in Chongqing from January 22 to February 25, 2010, and provide a series of suggestions for scientific prevention and control of epidemic situation, we will mainly analyze the epidemic situation data of Chongqing Municipal Health Committee members and improve the descriptive analysis. Regional distribution and spatiotemporal scans were analyzed for COVID-19 outbreaks using ArcGIS10.2 and SaTScan9. 5 software. After the analysis, a total of 576 novel coronavirus pneumonia patients were confirmed in Chongqing. The incidence trend increased rapidly from January 22 to January 31, then decreased gradually, and there were no new cases until February 25. The purely spatial scanning results were consistent with spatiotemporal scanning, and a first-level accumulation area was detected by spatiotemporal scanning in the east and northeast of Chongqing from January 22 to February 10. From January 22 to February 25, 2020,COVID-19 occurred in the eastern and northeast regions of Chongqing. It is recommended to strengthen the detection of cluster areas to prevent another outbreak of COVID-19 risk.

Epidemiologic and clinical characteristics of human bocavirus infection in children hospitalized for acute respiratory tract infection in Qingdao, China.

Persistent infection and prolonged shedding of human bocavirus 1 (HBoV1) in children have been reported, and the role of HBoV1 as a sole causative pathogen in acute respiratory infection (ARI) is yet to be established. While the reported prevalence of HBoV infection varies due to different detection methods and sampling criteria, determining the viral and bacterial etiology of HBoV infection using multiplex real-time PCR is yet to be reported. Herein, we aimed to further explore the pathogenicity of HBoV in patients with ARI by screening the viral and bacterial infections in children with ARI in Qingdao and comparing the epidemiological, clinical characteristics, and etiological results. Human bocavirus was identified in 28.1% of the samples, and further sequencing analysis of the detected HBoV confirmed 96.4% as HBoV1. The rate of HBoV as a single viral infection was 75%, and the rate of coinfection with bacteria was 66.1%, suggesting the need for continued monitoring of HBoV in children with ARIs. Clinical characterization suggested that HBoV infection may affect the function of organs, such as the liver, kidney, and heart, and the blood acid-base balance. Additionally, it is essential to promote awareness about the importance of disinfection and sterilization of the hospital environment and standardizing operations. The interactions between HBoV and other pathogens remain to be investigated in further detail in the future.

Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding.

Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.

Barriers to e-Learning during Crisis: A Capital Theory Perspective on Academic Adversity

The unprecedented coronavirus pandemic (COVID-19) presented new, daunting academic adversities to college students, especially those from underserved communities. This study provides a nuanced understanding of underserved students' adversities in online distance education, based on an in-depth analysis of narratives of 220 students from a minority-serving institution in the United States. Informed by the capital theory, the study revealed six major barriers to e-learning: technical, cultural, environmental, balance, social, and financial barriers, and identified new underlying dimensions. Moreover, the study found that technical barriers are often coupled with other types of barriers and underserved students are more likely to experience multiple learning barriers. A variance model of influencing factors was proposed for e-learning outcomes. The paper highlights new digital divide in e-learning and provides practical implications for educational institutions to support underserved students in overcoming academic adversities and building educational resilience.

Family supportive supervisor behavior and promotive voice: When and why are there gender differences in work–family?

PurposeThe purpose of this study is to examine the differential association of family supportive supervisor behavior on promotive voice under different gender. Further, while employees’ self-concept factors have received considerable attention in the research on the triggering mechanism of employee voice, the authors’ knowledge about how and when family factors affect employee voice remains underdeveloped.Design/methodology/approachAccording to the resource conservation theory and gender role theory, the authors constructed a research model to investigate the influence and boundary of family supportive supervisor behavior on employee promotive voice and tested their research model using a paired data of 332 married employees and their direct supervisors of enterprises in China.FindingsThe findings suggest that family supportive supervisor behavior has a positive effect on employee promotive voice. Family supportive supervisor behavior can strengthen employee promotive voice by improving work-to-family enrichment and reducing work–family conflict, yet no significant mediation effect was found regarding family-to-work enrichment and conflict. Furthermore, family supportive supervisor behavior is more likely to improve female employee work–family enrichment and assuage male employee work–family conflict and thus enhance employee promotive voice.Originality/valueThis study sheds light on the different influential paths of family supportive supervisor behavior on promotive voice of employees of different genders and provides references for enterprises to motivate employees’ promotive voice.