Ph-Positive B-Cell Acute Lymphoblastic Leukemia Occurring after Receipt of Bivalent SARS-CoV-2 mRNA Vaccine Booster: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world's population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph-positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required.

Fatal Fulminant Cerebral Edema in Six Children with SARS-CoV-2 Omicron BA.2 Infection in Taiwan.

Acute fulminant cerebral edema in children following SARS-CoV-2 infection has been rarely reported. Such patients frequently demonstrate rapid progression rapid progression and are usually fatal. In this retrospective study, we describe the detailed clinical, laboratory, and neuroimaging features of six fatal cases in Taiwan. All patients had shock initially, five showed rapid progression to multi-organ failure and disseminated intravascular coagulation, and three developed acute respiratory distress syndromes. The inflammatory biomarkers in the first 3 days, including interleukin 6, ferritin, lactate dehydrogenase and D-dimer, showed significant elevation in all cases. Hyper-inflammatory response may play a role in the pathophysiology.

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy.

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.

Predicting Risks of a COVID-19 Outbreak by Using Outdoor Air Pollution Indicators and Population Flow with Queuing Theory

COVID-19 has been widespread in all countries since it was first discovered in December 2019. The high infectivity of COVID-19 is primarily transmitted between people via respiratory droplets on contact routes, which makes it more difficult to prevent it. Air quality has been considered to be highly correlated with respiratory diseases. In addition, population movement increases contact routes, which increases the risk of COVID-19 outbreaks. For epidemic prevention, the government's strategies are also one of the factors that affect the risk of outbreaks, including whether it is mandatory to wear masks, stay-at-home orders, or vaccination. Wearing masks can reduce the risk of droplet infection, while stay-at-home orders can reduce contact between people. In this study, the number of COVID-19 confirmed cases and active cases of COVID-19 will be estimated according to the population movement, outdoor air pollution, and vaccination rates. Using the estimated results, the average recovery time will be predicted by Queuing Theory. The predicted average recovery time will be brought into risk analysis to estimate the possible high-risk periods. We compare the estimated high-risk periods with epidemic-prevention measures to provide a reference to evaluate the epidemic prevention plans enforced by relevant government agencies to achieve an improved control measure over the epidemic situation.

Exploring the Impacts of Preventative Health Behaviors with Respect to COVID-19: An Altruistic Perspective.

This study aims to explore the impact of gender and anxiety on various preventative health behaviors, and the relationships among these preventative health behaviors, individual well-being and depression, from the perspective of altruism. This study employed an online questionnaire survey, and 136 males and 204 females participated in the survey. The results of this study showed that females exhibited better preventative health behaviors than males, including hygiene habits, social distancing and behaviors intended to help others mitigate the epidemic. Anxiety regarding COVID-19 infection encouraged individuals to adopt hygienic habits and social distancing measures rather than to help others mitigate the epidemic. Hygiene habits improved the individual's psychological well-being. Helping others mitigate the epidemic improved the individual's psychological well-being and social well-being and contributed to reducing individual depression. However, the preventative health behavior involved in social distancing was not conducive to emotional well-being or social well-being. Affective elements are related to individual behaviors. Therefore, the use of prosocial, altruistic language may play an important role with respect to encouraging people to comply with preventative health behaviors in the context of COVID-19. In addition, it is worth noting that different preventative health behaviors may have different effects on people's mental health, especially when implementing social distancing-related epidemic mitigation behaviors. The question of how to prevent negative psychological effects in restricted actors must be answered, and the degree of life satisfaction experienced by those actors must also be taken into account.

Exploring the Impacts of Preventative Health Behaviors with Respect to COVID-19: An Altruistic Perspective

This study aims to explore the impact of gender and anxiety on various preventative health behaviors, and the relationships among these preventative health behaviors, individual well-being and depression, from the perspective of altruism. This study employed an online questionnaire survey, and 136 males and 204 females participated in the survey. The results of this study showed that females exhibited better preventative health behaviors than males, including hygiene habits, social distancing and behaviors intended to help others mitigate the epidemic. Anxiety regarding COVID-19 infection encouraged individuals to adopt hygienic habits and social distancing measures rather than to help others mitigate the epidemic. Hygiene habits improved the individual's psychological well-being. Helping others mitigate the epidemic improved the individual's psychological well-being and social well-being and contributed to reducing individual depression. However, the preventative health behavior involved in social distancing was not conducive to emotional well-being or social well-being. Affective elements are related to individual behaviors. Therefore, the use of prosocial, altruistic language may play an important role with respect to encouraging people to comply with preventative health behaviors in the context of COVID-19. In addition, it is worth noting that different preventative health behaviors may have different effects on people's mental health, especially when implementing social distancing-related epidemic mitigation behaviors. The question of how to prevent negative psychological effects in restricted actors must be answered, and the degree of life satisfaction experienced by those actors must also be taken into account.

Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury.

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.

A Structural Comparison of SARS-CoV-2 Main Protease and Animal Coronaviral Main Protease Reveals Species-Specific Ligand Binding and Dimerization Mechanism.

Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.

A Structural Comparison of SARS-CoV-2 Main Protease and Animal Coronaviral Main Protease Reveals Species-Specific Ligand Binding and Dimerization Mechanism

Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46–49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.

The low-entropy hydration shell at the binding site of spike RBD determines the contagiousness of SARS-CoV-2 variants (preprint)

The infectivity of SARS-CoV-2 depends on the binding affinity of the receptor-binding domain (RBD) of the spike protein with the angiotensin converting enzyme 2 (ACE2) receptor. The calculated RBD-ACE2 binding energies indicate that the difference in transmission efficiency of SARS-CoV-2 variants cannot be fully explained by electrostatic interactions, hydrogen-bond interactions, van der Waals interactions, internal energy, and nonpolar solvation energies. Here, we demonstrate that low-entropy regions of hydration shells around proteins drive hydrophobic attraction between shape-matched low-entropy regions of the hydration shells, which essentially coordinates protein-protein binding in rotational-configurational space of mutual orientations and determines the binding affinity. An innovative method was used to identify the low-entropy regions of the hydration shells of the RBDs of multiple SARS-CoV-2 variants and the ACE2. We observed integral low-entropy regions of hydration shells covering the binding sites of the RBDs and matching in shape to the low-entropy region of hydration shell at the binding site of the ACE2. The RBD-ACE2 binding is thus found to be guided by hydrophobic collapse between the shape-matched low-entropy regions of the hydration shells. A measure of the low-entropy of the hydration shells can be obtained by counting the number of hydrophilic groups expressing hydrophilicity within the binding sites. The low-entropy level of hydration shells at the binding site of a spike protein is found to be an important indicator of the contagiousness of the coronavirus.

Content analysis of COVID-19 rumors

Objectives: This study provided a basis for the public to evaluate numerous sources of COVID-19 information to mitigate the harm caused by the repeated dissemination and sharing of misinformation. Methods: Content analysis was used to examine the spread of COVID-19 rumors on the Internet. The content characteristics and expressions of 113 COVID-19 rumors collected from the "Taiwan Fact Checking Center" website were used as samples for analysis. Results: The most common type of COVID-19 rumor was "aggressive," and "a particular behavior" and "specific type of food or appliance" were the most common objects of the rumors. The dates of occurrence were not clearly noted, but the contents of more than half of the rumors were accurately described. The main purposes were primarily "attention/warning" and "sharing new knowledge." These rumors mostly originated from the Internet, and the rumors were corroborated primarily by "photos/icons/videos" and "experts." Conclusions: The content analysis results of the COVID-19 rumors could enhance the public's basic awareness and ability to identify false COVID-19 rumors and to encourage social media users to be more vigilant against the spread of disinformation.

Knowledge, Attitude, and Practice (KAP) toward COVID-19 Pandemic among the Public in Taiwan: A Cross-Sectional Study.

Purpose: Knowledge, attitude, and practice (KAP) models are often used by researchers in the field of public health to explore people's healthy behaviors. Therefore, this study mainly explored the relationships among participants' sociodemographic status, COVID-19 knowledge, affective attitudes, and preventive behaviors. Method: This study adopted an online survey, involving a total of 136 males and 204 females, and used a cross-sectional study to investigate the relationships between variables including gender, age, COVID-19 knowledge, positive affective attitudes (emotional wellbeing, psychological wellbeing, and social wellbeing), negative affective attitudes (negative self-perception and negative perceptions of life), and preventive behaviors (hygiene habits, reducing public activities, and helping others to prevent the epidemic). Results: The majority of participants in the study were knowledgeable about COVID-19. The mean COVID-19 knowledge score was 12.86 (SD = 1.34, range: 7-15 with a full score of 15), indicating a high level of knowledge. However, the key to decide whether participants adopt COVID-19 preventive behaviors was mainly their affective attitudes, especially positive affective attitudes (ß = 0.18-0.25, p< 0.01), rather than COVID-19 disease knowledge (ß = -0.01-0.08, p > 0.05). In addition, the sociodemographic status of the participants revealed obvious differences in the preventive behaviors; females had better preventive behaviors than males such as cooperating with the epidemic prevention hygiene habits (t = -5.08, p< 0.01), reducing public activities (t = -3.00, p< 0.01), and helping others to prevent the epidemic (t = -1.97, p< 0.05), while the older participants were more inclined to adopt preventive behaviors including epidemic prevention hygiene habits (ß = 0.18, p = 0.001, R2 = 0.03), reducing public activities (ß = 0.35, p< 0.001, R2 = 0.13), and helping others to prevent the epidemic (ß = 0.27, p< 0.001, R2 = 0.07). Conclusions: Having adequate COVID-19 knowledge was not linked to higher involvement in precautionary behaviors. Attitudes toward COVID-19 may play a more critical function in prompting individuals to undertake preventive behaviors, and different positive affective attitudes had different predictive relationships with preventive behaviors.

The Relationships among Anxiety, Subjective Well-Being, Media Consumption, and Safety-Seeking Behaviors during the COVID-19 Epidemic.

The COVID-19 epidemic has been confirmed as the largest scale outbreak of atypical pneumonia since the outbreak of severe acute respiratory syndrome (SARS) in 2003 and it has become a public health emergency of international concern. It exacerbated public confusion and anxiety, and the impact of COVID-19 on people needs to be better understood. Indeed, prior studies that conducted meta-analysis of longitudinal cohort research compared mental health before versus during the COVID-19 pandemic and proved that public health polices (e.g., city lockdowns, quarantines, avoiding gatherings, etc.) and COVID-19-related information that circulates on new media platforms directly affected citizen's mental health and well-being. Hence, this research aims to explore Taiwanese people's health status, anxiety, media sources for obtaining COVID-19 information, subjective well-being, and safety-seeking behavior during the COVID-19 epidemic and how they are associated. Online surveys were conducted through new media platforms, and 342 responses were included in the analysis. The research results indicate that the participants experienced different aspects of COVID-19 anxiety, including COVID-19 worry and perceived COVID-19 risk. Among the given media sources, the more participants searched for COVID-19 information on new media, the greater they worried about COVID-19. Furthermore, COVID-19 worry was positively related to safety-seeking behavior, while perceived COVID-19 risk was negatively related to subjective well-being. This paper concludes by offering some suggestions for future studies and pointing out limitations of the present study.

New Media Literacy, Health Status, Anxiety, and Preventative Behaviors Related to COVID-19: A Cross-Sectional Study in Taiwan.

Internet media may exacerbate public confusion and anxiety about COVID-19. New media health literacy (NMHL) is considered to play a protective role against health-related misinformation from the media for individuals to maintain their health. The current study aims to examine the relationship among Taiwanese adults' NMHL, health status, anxiety, and prevention behaviors during the COVID-19 pandemic. This cross-sectional study was conducted through an online survey, and 342 responses were included in the analysis. The survey tools include Health Status, COVID-19-Related New Media Health Literacy, COVID-19 Anxiety, and COVID-19 Preventive Behaviors. The research showed that both functional and critical prosuming literacy had positive relationships with health status. Functional consumption literacy had a weak negative correlation with COVID-19 anxiety. Furthermore, critical consumption literacy had a positive relationship with COVID-19 preventive behaviors. Therefore, individuals' health, anxiety, and prevention behaviors are affected by different aspects of COVID-19-related new media health literacy. Compared to their consuming media literacy, Taiwanese adults have insufficient prosuming media literacy in regard to COVID-19 health issues.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Respiratory care for the critical patients with 2019 novel coronavirus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets, aerosols and close contact. Cross infections occur because viruses spread rapidly among humans. Nineteen percent (19%) of the infected patients developed severe pneumonia and acute respiratory distress syndrome (ARDS). Hypoxemia usually occurs and patients may require oxygen therapy or mechanical ventilation (MV) support. In this article, recently published clinical experience and observational studies were reviewed. Corresponding respiratory therapy regarding different stages of infection is proposed. Infection control principles and respiratory strategies including oxygen therapy, non-invasive respiratory support (NIRS), intubation evaluation, equipment preparation, ventilator settings, special maneuvers comprise of the prone position (PP), recruitment maneuver (RM), extracorporeal membrane oxygenation (ECMO), weaning and extubation are summarized. Respiratory equipment and device disinfection recommendations are worked up. We expect this review article could be used as a reference by healthcare workers in patient care while minimizing the risk of environmental contamination.

Procrastination predicts online self-regulated learning and online learning ineffectiveness during the coronavirus lockdown.

During the lockdown due to SARS-CoV-2 (coronavirus lockdown), there has been a tremendous increase in the number of students taking online courses. Few studies, however, have examined the individual dispositions that influence self-regulated online learning during the coronavirus lockdown. To address this gap, the present study explored the ineffectiveness of online learning and examined how it can be predicted by self-regulated online learning and participants' procrastination disposition. Data of 433 participants were collected and subjected to confirmatory factor analysis with structural equation modeling. The results indicated that procrastination is negatively related to 6 sub-constructs of self-regulated online learning: task strategy, mood adjustment, self-evaluation, environmental structure, time management, and help-seeking. These sub-constructs were negatively related to the learners' perceived ineffectiveness of online learning. However, the relationship between perceived learning ineffectiveness and environmental structure or help-seeking was weaker than that with task strategy or mood adjustment, indicating that the latter two subtypes of self-regulated online learning should be considered before students engage in online learning.

Universal Urban Spreading Pattern of COVID-19 and Its Underlying Mechanism (preprint)

Currently, the global situation of COVID-19 is aggravating, pressingly calling for efficient control and prevention measures. Understanding spreading pattern of COVID-19 has been widely recognized as a vital step for implementing non-pharmaceutical measures. Previous studies investigated such an issue in large-scale (e.g., inter-country or inter-state) scenarios while urban spreading pattern still remains an open issue. Here, we fill this gap by leveraging the trajectory data of 197,808 smartphone users (including 17,808 anonymous confirmed cases) in 9 cities in China. We find a universal spreading pattern in all cities: the spatial distribution of confirmed cases follows a power-law-like model and the spreading centroid is time-invariant. Moreover, we reveal that human mobility in a city drives the spatialtemporal spreading process: long average travelling distance results in a high growth rate of spreading radius and wide spatial diffusion of confirmed cases. With such insight, we adopt Kendall model to simulate urban spreading of COVID-19 that can well fit the real spreading process. Our results unveil the underlying mechanism behind the spatial-temporal urban evolution of COVID-19, and can be used to evaluate the performance of mobility restriction policies implemented by many governments and to estimate the evolving spreading situation of COVID-19.

CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases (preprint)

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.