Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients. Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression. Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination. Conclusion: COVID-19 vaccination has no long-term impact on MG relapse.

The risk of intrauterine exposure to SARS-CoV-2 in female COVID-19 patients: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that has caused fatal infectious diseases and global spread. This novel coronavirus attacks target cells through the interaction of spike protein and angiotensin-converting enzyme II (ACE2), leading to different clinical symptoms. However, for a successful pregnancy, a well-established in-uterine environment includes a specific immune environment, and multi-interactions between specific cell types are prerequisites. The immune-related changes in patients infected with novel coronavirus could interfere with the immune microenvironment in the uterus, leading to fetal loss. We first reviewed the intrauterine environment in the normal development process and the possible pregnancy outcome in the infection state. Then, we summarized the immune response induced by SARS-CoV-2 in patients and analyzed the changes in ACE2 expression in the female reproductive system. Finally, the present observational evidence of infection in pregnant women was also reviewed.

The negative health effects of anti-Asian stigma in the U.S. during COVID-19

This study provided a systemic review of the content of 50 behavioral and social science studies investigating enactment and outcomes of anti-Asian stigma related to coronavirus disease (COVID-19) published in the final quarter of 2020 and during 2021. Based on a systematic search of several databases in December of 2021, 500 studies describing the impact of COVID-related stigma on Asian Americans were identified. From this group, 50 studies meeting the inclusion criteria were analyzed focusing on health and social consequences of stigma. The studies were described by five stigma themes: the enactment of stigma, health consequences of stigma, stigma in the social media, Asian American stigma in education, and policy and political consequences of anti-Asian stigma. The studies appeared in a wide range of scholarly journals using several methodologies. While some studies exclusively focused on health impacts of stigma, all considered how Asian Americans have been scapegoated for COVID-19. Spread of blame and digital stigma on the social media has been particularly damaging to psychological well-being. Discussion of these studies provided an informative systemic overview for how scholars from various disciplines have investigated the antecedents and possible mechanisms leading to anti-Asian hate. This study serves as a baseline for other scholars who want to build on this body of research in future studies as Omicron and other potential future variants of COVID unfold. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Rational development of multicomponent mRNA vaccine candidates against mpox.

The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.

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.

COVID-19 Hospitalization Trends in Rural Versus Urban Areas in the United States.

Since the summer of 2020, the rate of coronavirus cases in the United States has been higher in rural areas than in urban areas, raising concerns that patients with coronavirus disease 2019 (COVID-19) will overwhelm under-resourced rural hospitals. Using data from the University of Minnesota COVID-19 Hospitalization Tracking Project and the U.S. Department of Health and Human Services, we document disparities in COVID-19 hospitalization rates between rural and urban areas. We show that rural-urban differences in COVID-19 admission rates were minimal in the summer of 2020 but began to diverge in fall 2020. Rural areas had statistically higher hospitalization rates from September 2020 through early 2021, after which rural-urban admission rates re-converged. The insights in this article are relevant to policymakers as they consider the adequacy of hospital resources across rural and urban areas during the COVID-19 pandemic.

Mental health status of infected children between 7 to 12 years old in Fangcang Shelter Hospital during the COVID-19 Shanghai lockdown in 2022: a cross-section study.

Background: There has been an increase in research on the potential adverse effects on children's mental health, especially depression and anxiety, during the coronavirus disease 2019 (COVID-19) pandemic over the past few months. Therefore, the aim of the present study was to investigate depression and anxiety symptoms among children in shelter hospitals during the 2022 Shanghai lockdown. Methods: A total of 98 infected children aged 7-12 years were enrolled in this study between April 19 and June 4, 2022. The Children's Depression Inventory (CDI), Anxiety Scale for Children-Autism Spectrum Disorder (ASC-ASD), and Anxiety Scale or Children-Autism Spectrum Disorder Parent Form (ASC-ADS-P) were used to assess children's depression and anxiety symptoms. Children's guardians completed the survey by verbally asking their child/children the questions. The guardians additionally completed the ASC-ASD-P. Results: The prevalence of depression and anxiety was 12.2% and 13.3%, respectively. A total of 66 respondents reported no physical symptoms. Linear regression showed that myalgia [7.198, 95% confidence interval (CI): 3.163-11.232], headache (7.189, 95% CI: 3.842-10.535) coryza (5.362, 95% CI: 2.654-8.070), and number of quarantine days (4.378, 95% CI: 3.409-5.348) were significantly correlated with higher levels of depression, whereas chills (14.337, 95% CI: 9.799-18.875), coryza (9.309, 95% CI: 6.467-12.152), headache (7.193, 95% CI: 3.182-11.204), myalgia (5.571, 95% CI: 0.684-10.459), number of quarantine days (3.190, 95% CI: 1.796-4.584), and gender (male) (-4.137, 95% CI: -6.609 to 1.665) were associated with anxiety scores. Persistent fever was correlated with depression (P=0.007), whereas physical discomfort, such as persistent fever, cough, sore throat, headache, myalgia, and coryza were correlated with anxiety (all P<0.05). Conclusions: The findings of the present study indicated a moderate prevalence of depression and anxiety among infected children in a shelter hospital during the 2022 Shanghai lockdown. Therefore, the findings of this study could provide scientific basis for the development of targeted psychological intervention. It could be helpful for policy-makers to focus on psychological health among infected children and help to optimize future interventions.

Awake prone positioning for patients with COVID-19 pneumonia in intensive care unit: A systematic review and meta-analysis.

Background: Awake prone positioning (APP) has been widely used in non-intubated COVID-19 patients during the pandemic. However, high-quality evidence to support its use in severe COVID-19 patients in an intensive care unit (ICU) is inadequate. Therefore, we aimed to assess the efficacy and safety of APP for intubation requirements and other important outcomes in this patient population. Methods: We searched for potentially relevant articles in PubMed, Embase, and the Cochrane database from inception to May 25, 2022. Studies focusing on COVID-19 adults in ICU who received APP compared to controls were included. The primary outcome was the intubation requirement. Secondary outcomes were mortality, ICU stay, and adverse events. Study quality was independently assessed, and we also conducted subgroup analysis, sensitivity analysis, and publication bias to explore the potential influence factors. Results: Ten randomized controlled trials with 1,686 patients were eligible. The quality of the included studies was low to moderate. Overall, the intubation rate was 35.2% in the included patients. The mean daily APP duration ranged from <6 to 9 h, with poor adherence to APP protocols. When pooling, APP significantly reduced intubation requirement (risk ratio [RR] 0.84; 95%CI, 0.74-0.95; I 2 = 0%, P = 0.007). Subgroup analyses confirmed the reduced intubation rates in patients who were older (≥60 years), obese, came from a high mortality risk population (>20%), received HFNC/NIV, had lower SpO2/FiO2 (<150 mmHg), or undergone longer duration of APP (≥8 h). However, APP showed no beneficial effect on mortality (RR 0.92 [95% CI 0.77-1.10; I 2 = 0%, P = 0.37] and length of ICU stay (mean difference = -0.58 days; 95% CI, -2.49 to 1.32; I 2 = 63%; P = 0.55). Conclusion: APP significantly reduced intubation requirements in ICU patients with COVID-19 pneumonia without affecting the outcomes of mortality and ICU stay. Further studies with better APP protocol adherence will be needed to define the subgroup of patients most likely to benefit from this strategy.

Integration of protein context improves protein-based COVID-19 patient stratification.

BACKGROUND: Classification of disease severity is crucial for the management of COVID-19. Several studies have shown that individual proteins can be used to classify the severity of COVID-19. Here, we aimed to investigate whether integrating four types of protein context data, namely, protein complexes, stoichiometric ratios, pathways and network degrees will improve the severity classification of COVID-19. METHODS: We performed machine learning based on three previously published datasets. The first was a SWATH (sequential window acquisition of all theoretical fragment ion spectra) MS (mass spectrometry) based proteomic dataset. The second was a TMTpro 16plex labeled shotgun proteomics dataset. The third was a SWATH dataset of an independent patient cohort. RESULTS: Besides twelve proteins, machine learning also prioritized two complexes, one stoichiometric ratio, five pathways, and five network degrees, resulting a 25-feature panel. As a result, a model based on the 25 features led to effective classification of severe cases with an AUC of 0.965, outperforming the models with proteins only. Complement component C9, transthyretin (TTR) and TTR-RBP (transthyretin-retinol binding protein) complex, the stoichiometric ratio of SAA2 (serum amyloid A proteins 2)/YLPM1 (YLP Motif Containing 1), and the network degree of SIRT7 (Sirtuin 7) and A2M (alpha-2-macroglobulin) were highlighted as potential markers by this classifier. This classifier was further validated with a TMT-based proteomic data set from the same cohort (test dataset 1) and an independent SWATH-based proteomic data set from Germany (test dataset 2), reaching an AUC of 0.900 and 0.908, respectively. Machine learning models integrating protein context information achieved higher AUCs than models with only one feature type. CONCLUSION: Our results show that the integration of protein context including protein complexes, stoichiometric ratios, pathways, network degrees, and proteins improves phenotype prediction.

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.

WeChat users’ debunking strategies in response to COVID-19 conspiracy theories: A mixed-methods study

The current study adopted a mixed-methods approach to examine both qualitative and quantitative data of Chinese WeChat users? strategies in response to COVID-19 conspiracy theories disseminated in WeChat. Thematic analysis based on 30 interviewees suggested interesting patterns about how such conspiracy theories were disseminated based on relationship types within WeChat groups and how different types of debunking strategies were used to counter conspiracy theories based on the relational outcomes and contexts. Quantitative data based on 588 participants suggested COVID-19 information exposures from different sources, conspiracy beliefs, exposures of conspiracy beliefs and face concerns influence WeChat users? responses to address COVID-19-related information in WeChat platform.

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern.

COVID-19, an infectious disease caused by the SARS-CoV-2 virus, emerged globally in early 2020 and has remained a serious public health issue. To date, although several preventative vaccines have been approved by FDA and EMA, vaccinated individuals increasingly suffer from breakthrough infections. Therapeutic antibodies may provide an alternative strategy to neutralize viral infection and treat serious cases; however, the clinical data and our experiments show that some FDA-approved monoclonal antibodies lose function against COVID-19 variants such as Omicron. Therefore, in this study, we present a novel therapeutic agent, SI-F019, an ACE2-Fc fusion protein whose neutralization efficiency is not compromised, but actually strengthened, by the mutations of dominant variants including Omicron. Comprehensive biophysical analyses revealed the mechanism of increased inhibition to be enhanced interaction of SI-F019 with all the tested spike variants, in contrast to monoclonal antibodies which tended to show weaker binding to some variants. The results imply that SI-F019 may be a broadly useful agent for treatment of COVID-19.

The negative health effects of anti-Asian stigma in the U.S. during COVID-19

This study provided a systemic review of the content of 50 behavioral and social science studies investigating enactment and outcomes of anti-Asian stigma related to coronavirus disease (COVID-19) published in the final quarter of 2020 and during 2021. Based on a systematic search of several databases in December of 2021, 500 studies describing the impact of COVID-related stigma on Asian Americans were identified. From this group, 50 studies meeting the inclusion criteria were analyzed focusing on health and social consequences of stigma. The studies were described by five stigma themes: the enactment of stigma, health consequences of stigma, stigma in the social media, Asian American stigma in education, and policy and political consequences of anti-Asian stigma. The studies appeared in a wide range of scholarly journals using several methodologies. While some studies exclusively focused on health impacts of stigma, all considered how Asian Americans have been scapegoated for COVID-19. Spread of blame and digital stigma on the social media has been particularly damaging to psychological well-being. Discussion of these studies provided an informative systemic overview for how scholars from various disciplines have investigated the antecedents and possible mechanisms leading to anti-Asian hate. This study serves as a baseline for other scholars who want to build on this body of research in future studies as Omicron and other potential future variants of COVID unfold. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

A New Method Based on LAMP-CRISPR-Cas12a-Lateral Flow Immunochromatographic Strip for Detection.

INTRODUCTION: Carbapenemase-mediated antimicrobial resistance is currently a hot spot of global concern. Carbapenem-resistant organisms are highly prevalent in hospitals associated with difficult-to-treat infections, resulting in poor clinical outcome due to limited treatment options. It is urgently needed to have a rapid, efficient, and convenient molecular assay for identifying such resistant strains. METHODS: For this end, we developed a new laboratory assay targeting Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) based on loop-mediated isothermal amplification, CRISPR-Cas12a, and lateral flow immunochromatographic strip (CRISPR-Cas-LAMP-lateral flow strip). The method was designed to use a guide RNA (gRNA) to recognize the target DNA and guide Cas12a to cleave the target DNA, and simultaneously cleave any single-stranded DNA within the cleavage reaction system. RESULTS: The cleavage products are visible to the naked eye on the lateral flow strip. This method is highly sensitive in direct detection of bacteria in samples containing at least 3×105 CFU/mL without the need for bacterial culture. DISCUSSION: It provides shorter turnaround time and higher specificity than the conventional bacterial culture and susceptibility testing method. This new assay is applicable for extensive use in hospital infection control, as well as identification and treatment of resistant strains due to simple operation and inexpensive apparatuses.

Gut microbiota, inflammation, and molecular signatures of host response to infection.

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern

COVID-19, an infectious disease caused by the SARS-CoV-2 virus, emerged globally in early 2020 and has remained a serious public health issue. To date, although several preventative vaccines have been approved by FDA and EMA, vaccinated individuals increasingly suffer from breakthrough infections. Therapeutic antibodies may provide an alternative strategy to neutralize viral infection and treat serious cases;however, the clinical data and our experiments show that some FDA-approved monoclonal antibodies lose function against COVID-19 variants such as Omicron. Therefore, in this study, we present a novel therapeutic agent, SI–F019, an ACE2-Fc fusion protein whose neutralization efficiency is not compromised, but actually strengthened, by the mutations of dominant variants including Omicron. Comprehensive biophysical analyses revealed the mechanism of increased inhibition to be enhanced interaction of SI–F019 with all the tested spike variants, in contrast to monoclonal antibodies which tended to show weaker binding to some variants. The results imply that SI–F019 may be a broadly useful agent for treatment of COVID-19. Graphical Image 1

Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

Recent progress in the development of potential drugs against SARS-CoV-2.

SARS-CoV-2, a newly emerged and highly pathogenic coronavirus, is identified as the causal agent of Coronavirus Disease (2019) (COVID-19) in the late December 2019, in China. The virus has rapidly spread nationwide and spilled over to the other countries around the globe, resulting in more than 120 million infections and 2.6 million deaths until the time of this review. Unfortunately, there are still no specific drugs available against this disease, and it is very necessary to call upon more scientists to work together to stop a further spread. Hence, the recent progress in the development of drugs may help scientific community quickly understand current research status and further develop new effective drugs. Herein, we summarize the cellular entry and replication process of this virus and discuss the recent development of potential viral based drugs that target bio-macromolecules in different stages of the viral life cycle, especially S protein, 3CLPro, PLPro, RdRp and helicase.