Development of a multiplex qRT-PCR assay for the detection of porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus and porcine Deltacoronavirus.

Currently, porcine coronaviruses are prevalent in pigs, and due to the outbreak of COVID-19, porcine coronaviruses have become a research hotspot. porcine epidemic diarrhea virus (PEDV), Transmissible Gastroenteritis Virus (TGEV), and Porcine Deltacoronavirus (PDCoV) mentioned in this study mainly cause diarrhea in pigs. These viruses cause significant economic losses and pose a potential public health threat. In this study, specific primers and probes were designed according to the M gene of PEDV, the S gene of TGEV, and the M gene of PDCoV, respectively, and TaqMan probe-based multiplex real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was developed for the simultaneous detection of PEDV, TGEV, and PDCoV. This method has high sensitivity and specificity, and the detection limit of each virus can reach 2.95 × 100 copies/µl. An assay of 160 clinical samples from pigs with diarrhea showed that the positive rates of PEDV, TGEV, and PDCoV were 38.13, 1.88, and 5.00%; the coinfection rates of PEDV+TGEV, PEDV+PDCoV, TGEV+PDCoV, PEDV+TGEV+PDCoV were 1.25, 1.25, 0, 0.63%, respectively. The positive coincidence rates of the multiplex qRT-PCR and single-reaction qRT-PCR were 100%. This method is of great significance for clinical monitoring of the porcine enteric diarrhea virus and helps reduce the loss of the breeding industry and control the spread of the disease.

Ultrasensitive detection of SARS-CoV-2 S protein with aptamers biosensor based on surface-enhanced Raman scattering.

A rapid and accurate diagnostic modality is essential to prevent the spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized spike protein deoxyribonucleic acid aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and Au nanoparticles modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobe. The SCAP substrate and SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate, which can generate ultra-strong "hot spots" to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform. This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus as low as 0.8 TU mL-1 in about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.

Proteomic screening identifies RPLp2 as a specific regulator for the translation of coronavirus.

Viral mRNA of coronavirus translates in an eIF4E-dependent manner, and the phosphorylation of eIF4E can modulate this process, but the role of p-eIF4E in coronavirus infection is not yet entirely evident. p-eIF4E favors the translation of selected mRNAs, specifically the mRNAs that encode proteins associated with cell proliferation, inflammation, the extracellular matrix, and tumor formation and metastasis. In the present work, two rounds of TMT relative quantitative proteomics were used to screen 77 cellular factors that are upregulated upon infection by coronavirus PEDV and are potentially susceptible to a high level of p-eIF4E. PEDV infection increased the translation level of ribosomal protein lateral stalk subunit RPLp2 (but not subunit RPLp0/1) in a p-eIF4E-dependent manner. The bicistronic dual-reporter assay and polysome profile showed that RPLp2 is essential for translating the viral mRNA of PEDV. RNA binding protein and immunoprecipitation assay showed that RPLp2 interacted with PEDV 5'UTR via association with eIF4E. Moreover, the cap pull-down assay showed that the viral nucleocapsid protein is recruited in m7GTP-precipitated complexes with the assistance of RPLp2. The heterogeneous ribosomes, which are different in composition, regulate the selective translation of specific mRNAs. Our study proves that viral mRNA and protein utilize translation factors and heterogeneous ribosomes for preferential translation initiation. This previously uncharacterized process may be involved in the selective translation of coronavirus.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Masks for COVID-19.

Sustainable solutions on fabricating and using a face mask to block the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread during this coronavirus pandemic of 2019 (COVID-19) are required as society is directed by the World Health Organization (WHO) toward wearing it, resulting in an increasingly huge demand with over 4 000 000 000 masks used per day globally. Herein, various new mask technologies and advanced materials are reviewed to deal with critical shortages, cross-infection, and secondary transmission risk of masks. A number of countries have used cloth masks and 3D-printed masks as substitutes, whose filtration efficiencies can be improved by using nanofibers or mixing other polymers into them. Since 2020, researchers continue to improve the performance of masks by adding various functionalities, for example using metal nanoparticles and herbal extracts to inactivate pathogens, using graphene to make masks photothermal and superhydrophobic, and using triboelectric nanogenerator (TENG) to prolong mask lifetime. The recent advances in material technology have led to the development of antimicrobial coatings, which are introduced in this review. When incorporated into masks, these advanced materials and technologies can aid in the prevention of secondary transmission of the virus.

The Associations of Lymphocyte Ratio and Neutrophil Ratio on Liver Dysfunction in COVID-19 Patients.

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.

Psychometric Properties of the Chinese Version of the Primary Care Post-Traumatic Stress Disorder Screen-5 for Medical Staff Exposed to the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic may increase the development of psychiatric disorders, such as posttraumatic stress disorder (PTSD) among medical staff. A brief validated screening tool is essential for the early diagnosis of PTSD. The purpose of the present study was to evaluate the validation of a Chinese version of the Primary Care-PTSD-5 (C-PC-PTSD-5) and determine an appropriate cutoff score with optimal sensitivity and specificity for medical staff in China during the COVID-19 pandemic. PARTICIPANTS AND METHODS: An online cross-sectional survey was conducted on medical staff (n = 1104) from 17 medical institutions in Shanghai. Questionnaires comprising general information, medical-related traumatic event experiences, the PTSD Checklist (PCL-5), and C-PC-PTSD-5 were distributed to participants using the online Questionnaire Star electronic system. Internal consistency, convergent validity, and test-retest reliability were calculated. Receiver operating characteristic (ROC) analysis was performed to determine diagnostic accuracy and the optimal cutoff score of the C-PC-PTSD-5 for medical staff. RESULTS: We included 1062 valid questionnaires for the analysis. Data of 838 traumatic experiences were analyzed. Internal consistency of the C-PC-PTSD-5 was satisfied (Cronbach's α = 0.756). The total score of the C-PC-PTSD-5 showed good test-retest reliability (r = 0.746). We found a strong correlation between the C-PC-PTSD-5 score and PCL-5 total score (r = 0.669, p < 0.001), which indicated good convergent validity. The ROC analysis showed an area under the curve of 0.81 ± 0.016. A cutoff score of 2 provided optimal sensitivity and specificity for the C-PC-PTSD-5 (sensitivity = 0.632, specificity = 0.871, Youden index = 0.503, and overall efficiency = 0.768). CONCLUSION: Our results indicated that the C-PC-PTSD-5 can be employed as a brief and efficient screening instrument for medical staff exposed to the COVID-19 pandemic. A score of 2 was identified as the optimal threshold for probable clinical PTSD symptoms.

The Effect of WeChat on Parental Care Burden, Anxiety, and Depression in Children after CHD Surgery during COVID-19 Pandemic.

OBJECTIVES: This study aimed to explore the effect of applying WeChat in the follow-up and health education of children after congenital heart disease (CHD) surgery during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: Data from 135 children were retrospectively analyzed. The care burden, anxiety, depression, and satisfaction of the parents of patients at home were analyzed and compared. RESULTS: One month after discharge, the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Zarit Burden Interview (ZBI), and Patient Satisfaction Questionnaire-18 scores of the WeChat follow-up group were significantly better than those of the outpatient follow-up group (p < 0.05). Compared with the discharge time, the SAS, SDS, and ZBI scores were significantly improved in the WeChat follow-up group but not in the outpatient follow-up group (p < 0.05). CONCLUSION: During the COVID-19 epidemic, the application of WeChat to the follow-up management of children after CHD surgery can effectively reduce care burden and relieve anxiety and depression in parents at home. It can also improve the satisfaction of parents with medical treatment.

SARS-CoV-2 infection in the mouse olfactory system.

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

Quantitative Structure-Property Relationships (QSPR) of Valency Based Topological Indices with Covid-19 drugs and Application

The purpose of this analysis is to establish a quantitative structure-property relationship (QSPR) between ev and ve-degree based topological descriptors and measured physicochemical parameters of phytochemicals screened against SARS-CoV-2 3CLpro. A computer-based algorithm is developed to compute the ev and ve-degree based topological indices for the considered graphs. Our study revealed that the ev-degree based Zagreb index Mev and ve-degree based first beta Zagreb index M1βve are two important topological indices that can be useful in the prediction of molecular weight and the topological polar surface area of phytochemicals. Applications to certain anticancer drug (Camptothecin-Polymer Conjugate IT-101) are presented at the end.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

Comparison of acute pneumonia caused by SARS-COV-2 and other respiratory viruses in children: a retrospective multi-center cohort study during COVID-19 outbreak.

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

DABC-Net for robust pneumonia segmentation and prediction of COVID-19 progression on chest CT scans (preprint)

Currently, reliable, robust and ready-to-use CT-based tools for prediction of COVID-19 progression are still lacking. To address this problem, we present DABC-Net, a novel deep learning (DL) tool that combines a 2D U-net for intra-slice spatial information processing, and a recurrent LSTM network to leverage inter-slice context, for automatic volumetric segmentation of lung and pneumonia lesions. We evaluate DABC-Net on more than 10,000 radiologists-labeled CT slices from four different cohorts. Compared to state-of-the-art segmentation tools, DABC-Net is much faster, more robust, and able to estimate segmentation uncertainty. Based only on the first two CT scans within 3 days after admission from 656 longitudinal CT scans, the AUC of our DBAC-Net for disease progression prediction reaches 93%. We release our tool as a GUI for patient-specific prediction of pneumonia progression, to provide clinicians with additional assistance to triage patients at early days after the diagnosis and to optimize the assignment of limited medical resources, which is of particular importance in current critical COVID-19 pandemic.

Increased Brain Volume from Higher Cereal and Lower Coffee Intake: Shared Genetic Determinants and Impacts on Cognition and Metabolism (preprint)

Background: It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part.Methods: We used cross-sectional observational data from UK Biobank. Only white British individuals free of Alzheimer's or dementia diseases were included in the study. We conducted linear regression analysis and mediation models to examine the association between diets, gerey matter volume, genetic variants, lifestyle, and metabolic measures. We tested the association between the GMV-association patterns of the cereal/coffee intake, the GMV-association patterns of cognitive functions and the gene-expression patterns.Findings: Overall, 336517 participants were included in our analysis. We discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. These genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions.Interpretation: Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.Funding Statement: This work received support from the following sources: the National Key Research and Development Program of China (2018YFC1312900 and 2019YFA0709502), the National Natural Science Foundation of China (91630314 and 81801773), the 111 Project (B18015), The Key Project of Shanghai Science &Technology Innovation Plan(16JC1420402), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and Zhangjiang Lab. Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: All participants provided written informed consent to UK Biobank. The UK Biobank study received ethical approval from the NHS National Research Ethics Service North West (reference number: 16/NW/0274). Data access permission was granted under UKB application 19542 (PI Jianfeng Feng).

Increased brain volume from higher cereal and lower coffee intake: Shared genetic determinants and impacts on cognition and metabolism (preprint)

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. The Mendelian randomisation approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated in the newly-released independent UK Biobank data from 16,412 healthy adults. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs. Significance statement We investigated diet effects on the brain structure and its genetic constructs using the UK Biobank data and discovered a causal effect of higher coffee intake on reduced total grey matter volume (GMV) and replicable anti-correlated brain-wide association GMV patterns between cereal and coffee intake. Further, the high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI, and other metabolic indicators. Our study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.