Kidney Health and Care: Current Status, Challenges, and Developments.

The concept of chronic kidney disease (CKD) originated in the 2000s, and an estimated 850 million patients are currently suffering from health threats from different degrees of CKD. However, it is unclear whether the existing CKD care systems are optimal for improving patient prognosis and outcomes, so this review summarizes the burden, existing care models, effectiveness, challenges, and developments of CKD care. Even under the general care principles, there are still significant gaps in our understanding of the causes of CKD, prevention or care resources, and care burdens between countries worldwide. Receiving care from multidisciplinary teams rather than only a nephrologist shows potential profits in comprehensive and preferable outcomes. In addition, we propose a novel CKD care structure that combines modern technologies, biosensors, longitudinal data visualization, machine learning algorithms, and mobile care. The novel care structure could simultaneously change the care process, significantly reduce human contact, and make the vulnerable population less likely to be exposed to infectious diseases such as COVID-19. The information offered should be beneficial, allowing us to rethink future CKD care models and applications to reach the goals of health equality and sustainability.

Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort.

BACKGROUND/AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. METHODS: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. RESULTS: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34-0.72, P < 0.001), female sex (OR/CI: 1.85/1.30-2.63, P = 0.001), Moderna-Moderna-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 6.49/3.90-10.83, P < 0.001), BNT-BNT-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 7.91/1.82-34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34-0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (ß: - 0.083; 95% CI: - 0.094-0.011, P = 0.014) independently correlated with low IgG spike antibody levels. CONCLUSIONS: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

A receptor-binding domain-based nanoparticle vaccine elicits durable neutralizing antibody responses against SARS-CoV-2 and variants of concern.

Numerous vaccines have been developed to address the current COVID-19 pandemic, but safety, cross-neutralizing efficacy, and long-term protectivity of currently approved vaccines are still important issues. In this study, we developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein. As compared with the aluminum-adjuvant RBD vaccine, ASD254 induced higher titers of RBD-specific antibodies and generated 10- to 30-fold more neutralizing antibodies. Mice vaccinated with ASD254 showed protective immune responses against SARS-CoV-2 challenge, with undetectable infectious viral loads and reduced typical lesions in lung. Besides, neutralizing antibodies in vaccinated mice lasted for at least one year and were effective against various SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, particle size, polydispersity index, and zeta potential of ASD254 remained stable after 8-month storage at 4°C. Thus, ASD254 is a promising nanoparticle vaccine with good immunogenicity and stability to be developed as an effective vaccine option in controlling upcoming waves of COVID-19.

Long-Range SERS Detection of the SARS-CoV-2 Antigen on a Well-Ordered Gold Hexagonal Nanoplate Film.

The development of an effective method for identifying severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) via direct viral protein detection is significant but challenging in combatting the COVID-19 epidemic. As a promising approach for direct detection, viral protein detection using surface-enhanced Raman scattering (SERS) is limited by the larger viral protein size compared to the effective electromagnetic field (E-field) range because only the analyte remaining within the E-field can achieve high detection sensitivity. In this study, we designed and fabricated a novel long-range SERS (LR-SERS) substrate with an Au nanoplate film/MgF2/Au mirror/glass configuration to boost the LR-SERS resulting from the extended E-field. On applying the LR-SERS to detect the SARS-CoV-2 spike protein (S protein), reagent-free detection achieved a low detection limit of 9.8 × 10-11 g mL-1 and clear discrimination from the SARS-CoV S protein. The developed technique also allows testing of the S protein in saliva with 98% sensitivity and 100% specificity.

Maternal-Neonatal Outcomes of Obstetric Deliveries Performed in Negative Pressure Isolation Rooms during the COVID-19 Omicron Variant Pandemic in Taiwan: A Retrospective Cohort Study of a Single Institution.

Objective: To investigate the maternal-neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal-neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.

Rhabdomyolysis in Pediatric Patients with SARS-CoV-2 Infection.

BACKGROUND: Rhabdomyolysis is a rare but severe complication in adult patients with Coronavirus disease 2019 (COVID-19), which can result in acute kidney injury and death; however, it is rarely reported in pediatric patients. METHODS: In this study, we retrospectively reviewed the clinical features and outcomes of rhabdomyolysis in pediatric patients aged 0-18 years with COVID-19 who were hospitalized at Taipei Tzu Chi Hospital, an epicenter of COVID-19 in northern Taiwan. RESULTS: We treated eight patients with rhabdomyolysis during the omicron variant-Severe acute respiratory syndrome coronavirus 2 (omicron variant-SARS-CoV-2) community outbreak and none during the alpha variant endemic. These eight patients shared stereotypical presentations, including the presence of bilateral calf pain after defervescence. The creatinine kinase (CK) levels were between 1346 and 6937 U/L on admission, and clinical course was uneventful after aggressive saline hydration. CONCLUSION: Rhabdomyolysis is not a rare complication in pediatric patients with the omicron-SARS-CoV-2 infection, and reassurance of a good prognosis is important to alleviate family anxiety.

Effectiveness of Booster and Influenza Vaccines against COVID-19 among Healthcare Workers, Taiwan.

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2.

Configurations for positive public behaviors in response to the COVID-19 pandemic: a fuzzy set qualitative comparative analysis.

BACKGROUND: The COVID-19 crisis poses considerable threats to public health, and exploring the key configuration conditions of the public behavior response is very important for emergency risk management. OBJECTIVE: This study attempts to reveal differences in the conditional configuration and mechanism of public behavior based on the proposed framework, further make up for the deficiencies of existing research in explaining such issues as "How to promote the public's protective behavior or reduce the public's excessive behavior?" and finally provide new evidence and ideas for the government to improve the emergency management system. METHODS: A total of 735 valid cases were obtained using an online survey and revealed the conditional configuration and mechanism of public behavior differences through a fuzzy set qualitative comparative analysis based on the proposed public behavioral framework. RESULTS: The results show that critical factors including risk communication, trust, risk perception, and negative emotions alone did not constitute a necessary condition for public protective or excessive behavior. The different configurations of influencing factors reveal the complexity of public behavioral risk management, and taking adequate measures to increase public trust and reduce negative public emotions constitute the core path of risk management to enhance positive public behavior. CONCLUSIONS: The configurations of various influencing factors reveal the complexity of public behavioral risk management. For behavioral risk management, governments should focus on adapting to multiple conditions according to their situations and, under the "overall perspective," formulate policies based on local conditions and further form a differentiated risk management path. Practically speaking, for the government, taking adequate measures to increase public trust and reduce negative public emotions is the core path of risk management to enhance positive public behavior.

An ultra-sensitive and specific nanoplasmonic-enhanced isothermal amplification platform for the ultrafast point-of-care testing of SARS-CoV-2.

The novel mutations attributed by the high mutagenicity of the SARS-CoV-2 makes its prevention and treatment challenging. Developing an ultra-fast, point-of-care-test (POCT) protocol is critical for responding to large-scale spread of SARS-CoV-2 in public places and in resource-poor remote areas. Here, we developed a nanoplasmonic enhanced isothermal amplification (NanoPEIA) strategy that combines a nanoplasmonic sensor with isothermal amplification. The novel strategy provides an ideal easy-to operate detection platform for obtaining accurate, ultra-fast and high-throughput (96 samples can be tested together) data. For clinical samples with viral detection at Ct value <25, the entire process (including sample preparation, virus lysis, detection, and data analysis) can be completed within six minutes. The method is also appropriate for detection of SARS-CoV-2 γ-coronavirus mutants. The NanoPEIA method was validated using clinical samples from 21 patients with SARS-CoV-2 infection and 31 healthy individuals. The detection result on the 52 clinical samples for SARS-CoV-2 showed that the NanoPEIA platform had a 100% sensitivity for N and orf1ab genes, which was higher than those obtained using RT-qPCR (88.9% and 90.0%, respectively). The specificities of 31 clinical negative samples were 92.3% and 91.7% for the N gene and the orf1ab gene, respectively. The limits of detection (LoD) of the clinical samples were 28.3 copies/mL and 23.3 copies/mL for the N gene and the orf1ab gene, respectively. The efficient NanoPEIA detection strategy facilitates real-time detection and visualization within ultrashort durations and can be applied for POCT diagnosis in resource-poor and highly populated areas.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Nightmares mediate the association between traumatic event exposure and suicidal ideation in frontline medical workers exposed to COVID-19.

BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.

Public Willingness and Determinants of COVID-19 Vaccination at the Initial Stage of Mass Vaccination in China.

The present study assessed the willingness of the general population to receive COVID-19 vaccines and identified factors that influence vaccine hesitancy and resistance. A national online survey was conducted from 29 January 2021 to 26 April 2021 in China. Multinomial logistic regression analyses were conducted to identify factors that influence vaccine hesitancy and resistance. Of the 34,041 participants surveyed, 18,810 (55.3%) were willing to get vaccinated, 13,736 (40.3%) were hesitant, and 1495 (4.4%) were resistant. Rates of vaccine acceptance increased over time, with geographical discrepancies in vaccine hesitancy and resistance between provinces in China. Vaccine safety was the greatest concern expressed by most participants (24,461 [71.9%]), and the major reason for participants' refusing vaccination (974 [65.2%]). Government agencies (23,131 [68.0%]) and social media (20,967 [61.6%]) were the main sources of COVID-19 vaccine information. Compared with vaccination acceptance, female, young and middle-aged, high income, and perceived low-risk of infection were associated with vaccine hesitancy. Histories of allergic reactions to other vaccines and depression symptoms were related to vaccine resistance. Common factors that influenced vaccine hesitancy and resistance were residing in cities and perceiving less protection with vaccines than with other protective measures. The results indicate that the rate of vaccine resistance is relatively low, but vaccine hesitancy is common. Individuals who are female, young and middle-aged, with a high income, and residing in cities are more likely to be hesitant for vaccination and should be the target populations for vaccination campaigns. Specific vaccine messaging from the government and social media could alleviate public concerns about vaccine safety and efficacy.

Characteristics, contacts, and relative risk of SARS-CoV-2 infection among children during school closures.

BACKGROUND: Characteristics of children with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Taiwanese households is nascent. We sought to characterize SARS-CoV-2 infection, and estimate the relative risk of infection among children within households during school closures in Taipei and New Taipei City. METHODS: We reviewed consecutive children below 18 years presenting to our emergency department from May 18, 2021 to July 12, 2021 who underwent real-time reverse-transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 from respiratory swabs. Demographics, symptoms, and contacts were captured from medical records. Household contact was defined as an individual with confirmed COVID-19 living in the same residence as the child. RESULTS: Among 56 children with SARS-CoV-2, twenty-five (45%) were male with mean age of 7.9 years. Symptoms were nonspecific, with 29% having fever, 32% having cough, and 48% were asymptomatic. The median cycle threshold (Ct) value of SARS-CoV-2 rRT-PCR was 25 (range 11-38). All 56 children reported 94 contacts with a COVID-19 patient, of which 99% were household contacts. The relative risk of infection was 8.5 (95% CI 5.0-14.7) for children whose parent(s) were COVID-19 patients, and 7.3 (95% CI 4.9-11.0) for children whose household grandparent(s) were patients, as compared to children without respective contacts. Children without COVID-19 contacts were all tested negative. CONCLUSIONS: During school closures in Taipei and New Taipei City, children with SARS-CoV-2 infection in our cohort had one or more COVID-19 contacts, mostly within their households. While diagnosing pediatric COVID-19 is challenging as children were often asymptomatic, those without contacts were likely uninfected.

Structure-guided antibody cocktail for prevention and treatment of COVID-19.

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.

Initial Public-Health Emergency Response to SARS and COVID-19 Pandemics in Mainland China: A Retrospective Comparative Study.

BACKGROUND: Severe acute respiratory syndrome (SARS) was reported first in China in 2003. The world is currently coping with coronavirus disease-2019 (COVID-19). We conducted a retrospective study to compare the initial public-health emergency response (PHER) to SARS and COVID-19 in mainland China. METHODS: A qualitative comparative study was conducted to compare the PHER timelines to SARS and COVID-19 by selecting six crucial time points. Besides, we explored the speed of spread, peak time and plateau period of SARS and COVID-19, respectively, by comparing the confirmed cases in the same time interval. RESULTS: The government of the People's Republic of China (PRC) accomplished the entire initial PHER to SARS in 127 days and for COVID-19 in 44 days. The speed of PHER for COVID-19 was 83 days faster. The peak time of SARS arose ~80 days later than that of COVID-19. Though the peak number of confirmed daily cases for COVID-19 was fivefold more than that of SARS, the onset of the stabilization period for COVID-19 was >2 months earlier than that of SARS. CONCLUSION: Overall, the speed of the initial PHER to COVID-19 pandemic was faster than that for SARS. Compared with the speed of hospital reporting and government policymaking, the speed of pathogen identification improved the most. The COVID-19 pandemic curve entered a plateau period earlier than the SARS pandemic curve, which suggests that the pandemic was controlled more effectively because of a timely PHER. The PRC government should emphasize improving the ability of hospitals to restrain infectious diseases by enhancing the direct reporting system and cultivating crisis management to empower relevant individuals to make timely scientific decisions.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). FINDING: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. INTERPRETATION: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. FUNDING: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

Trans-ethnic genome-wide association study of severe COVID-19.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

Current Status and Future Perspective of Artificial Intelligence in the Management of Peptic Ulcer Bleeding: A Review of Recent Literature.

With the decreasing incidence of peptic ulcer bleeding (PUB) over the past two decades, the clinician experience of managing patients with PUB has also declined, especially for young endoscopists. A patient with PUB management requires collaborative care involving the emergency department, gastroenterologist, radiologist, and surgeon, from initial assessment to hospital discharge. The application of artificial intelligence (AI) methods has remarkably improved people's lives. In particular, AI systems have shown great potential in many areas of gastroenterology to increase human performance. Colonoscopy polyp detection or diagnosis by an AI system was recently introduced for commercial use to improve endoscopist performance. Although PUB is a longstanding health problem, these newly introduced AI technologies may soon impact endoscopists' clinical practice by improving the quality of care for these patients. To update the current status of AI application in PUB, we reviewed recent relevant literature and provided future perspectives that are required to integrate such AI tools into real-world practice.

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.