Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Trends of obesity and overweight among children and adolescents in China.

BACKGROUND: Recent decades have shown a rapid increase in the prevalence of overweight and obesity among Chinese children based on several national surveys. Restrictions due to the coronavirus disease 2019 outbreak have worsened its epidemiology. This review updates the trends in the prevalence of overweight and obesity among Chinese children and adolescents and analyzes the underlying reasons to provide evidence for better policy making. METHODS: Studies published in English and Chinese were retrieved from PubMed, Google Scholar, China National Knowledge Infrastructure and Wanfang. RESULTS: The prevalence of overweight and obesity has been increasing for decades and varies with age, sex and geography but is more pronounced in primary school students. The increase in obesity in boys appeared to be slower, whereas that in girls showed a declining trend. The northern areas of China have persistently maintained the highest levels of obesity with a stable trend in recent years. Meanwhile, the prevalence in eastern regions has dramatically increased. Notably, the overall prevalence of obesity in children has shown a stabilizing trend in recent years. However, the occurrence of obesity-related metabolic diseases increased. The effect of migrants floating into east-coast cities should not be neglected. CONCLUSIONS: The high prevalence of overweight and obesity among Chinese children and adolescents persists but with varying patterns. Obesity-related metabolic diseases occur more frequently despite a stable trend of obesity. Multiple factors are responsible for the changing prevalence. Thus, comprehensive and flexible policies are needed to effectively manage and prevent the burden of obesity and its related complications.

Prevalence and patterns of major depressive disorder and subthreshold depressive symptoms in south China.

BACKGROUND: Information on major depressive disorder (MDD) and subthreshold depressive symptoms (SDS) is rarely reported in south China. This study examines the prevalence rates and patterns of MDD and SDS of a large representative sample of adult residents in south China. METHODS: The Guangdong Mental Health Survey was conducted on adults (over 18 years) from September to December 2021. Multistage stratified cluster sampling was used and face-to-face interviews were done with a two-stage design by trained lay interviewers and psychiatrists. A total of 16,377 inhabitants were interviewed using standardized assessment tools. Data were weighted to adjust for differential probabilities of selection and differential response. RESULTS: The weighted prevalence rates of MDD and SDS were 2.5 % (95%CI: 2.2 %-2.9 %) and 14.7 % (95%CI: 14.0 %-15.5 %), respectively. Multinomial logistic regression analysis revealed that female, younger age, living in urban area, higher education, unmarried, irregular meal pattern, lack of physical exercise, chronic diseases, irregular napping pattern and short sleep were positively associated with SDS. Besides, female, younger age, unmarried, irregular meal pattern, lack of physical exercise, chronic diseases, short sleep and poor mental health were positively associated with MDD. LIMITATIONS: The cross-sectional nature of the study limited causal inferences. CONCLUSIONS: The prevalence of MDD in Guangdong province in 2021 is higher than in mainland China in 2013. Given the higher prevalence of SDS, and high burden of depression, it also offers valuable opportunities for policymakers and health-care professionals to explore the factors affecting mental health in Guangdong province, especially during the COVID-19 epidemic.

Epidemiological investigation of the first locally acquired case of COVID-19 identified by influenza surveillance-Taiwan, February 2020.

BACKGROUND: COVID-19 and influenza have similar clinical presentations that can range from mild to severe disease. The World Health Organization recommends that countries use existing influenza surveillance to monitor COVID-19 transmission in communities. We aim to describe the surveillance and investigation of COVID-19 at the early stage of the pandemic in Taiwan. METHODS: In February 2020, the Taiwan Centers for Disease Control enhanced COVID-19 surveillance through its existing influenza surveillance. We retrospectively tested patients for SARS-CoV-2 who had symptoms of severe complicated influenza but were negative in influenza testing. We conducted an epidemiological investigation and contact tracing for the index patient and secondary cases to prevent virus transmission. RESULTS: We identified the first COVID-19 patient on February 15 through enhanced COVID-19 surveillance. He had no history of traveling abroad and an unclear history of contact with COVID-19 cases. He presented with influenza-like illness on January 27 and was hospitalized from February 3 to 15. We identified 39 close contacts of the index patient, including 11 family members and 28 healthcare workers. In total, four close family contacts of the index patient tested positive for SARS-CoV-2. An additional 84 close contacts of the four secondary cases were identified and traced; none was diagnosed with COVID-19. CONCLUSIONS: We recommend enhancing COVID-19 surveillance by testing patients with influenza-like illness. To prevent the spread of COVID-19, we recommend using appropriate personal protective equipment when in close contact with patients who present with influenza-like illness or when caring for patients with pneumonia of unknown etiology.

Structural Evolution and Community Detection of China Rail Transit Route Network

How to improve the partial or overall performance of rail transit route network, strengthen the connection between different rail network stations, and form corresponding communities to resist the impact of sudden or long-term external factors has earned a lot of attention recently. However, the corresponding research studies are mostly based on the rail network structure, and the analysis and exploration of the community formed by the stations and its robustness are not enough. In this article, the evolution of the China rail transit route network (CRTRN) from 2009 to 2022 is taken as the research object, and its complex network characteristics, BGLL model-based community division, and multi disturbance strategies for network robustness are analyzed in depth to better understand and optimize the rail network structure to further effectively improve the efficiency of the public transport system. It is found that CRTRN is gradually expanding following the southwest direction (with the migration distance of nearly 200 km), the distribution of routes is more balanced, and the number of network communities is steadily decreasing (it dropped from 30 communities in 2009 to 25 in 2019), making various regions become closely connected. However, it can also be found that during the COVID-19 pandemic, the CRTRN is strongly affected, and the network structure becomes relatively loose and chaotic (the number of communities became 30). To protect the railway networks, the CRTRN system should pay more attention to stations with high node degree values;if they get disturbed, more areas will be affected. The corresponding research conclusions can provide some theoretical and practical support for the construction of the rail transit network in China.

Construction and Immunogenicity of a Recombinant Pseudorabies Virus Expressing SARS-CoV-2-S and SARS-CoV-2-N

Coronavirus (CoV) is an important pathogen of humans and animals, which can infect humans or animals through the respiratory mucosal route. Syndrome coronavirus 2 (SARS-CoV-2) is quite similar to syndrome coronavirus (SARS-CoV) with the same receptor, angiotensin-converting enzyme 2 (ACE2). The S and N proteins are the most important protective antigens of the SARS-CoV-2. The S protein on the viral membrane mediates the virus attachment with the host cells, and the N protein is the most abundant expression during infection. In this study, the recombinant viruses expressing the S and N proteins of SARS-CoV-2 were successfully constructed by Red/ET recombinant technology using Pseudorabies virus (PRV) strain Bartha-K61 as a vector. Genetic stability and growth kinetics analysis showed that the recombinant viruses rPRV-SARS-CoV-2-S and rPRV-SARS-CoV-2-N had similar genetic stability and proliferation characteristics to the parental PRV. The immunoassay results showed that mice immunized with recombinant viruses could produce total IgG antibodies. Therefore, PRV is feasible and promising as a viral vector to express SARS-CoV-2-S and SARS-CoV-2-N genes. This study can provide a reference for future research on live vector vaccines for domestic animals, pets, and wild animals.

Mapping Network Connectivity Among Symptoms of Depression and Pain in Wuhan Residents During the Late-Stage of the COVID-19 Pandemic.

Background: Symptoms of depression and pain often overlap, and they negatively influence the prognosis and treatment outcome of both conditions. However, the comorbidity of depression and pain has not been examined using network analysis, especially in the context of a pandemic. Thus, we mapped out the network connectivity among the symptoms of depression and pain in Wuhan residents in China during the late stage of the COVID-19 pandemic. Methods: This cross-sectional study was conducted from May 25, 2020 to June 18, 2020 in Wuhan, China. Participants' depressive and pain symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ9) and a pain numeric rating scale (NRS), respectively. Network analyses were performed. Results: In total, 2,598 participants completed all assessments. PHQ4 (fatigue) in the depression community showed the highest strength value, followed by PHQ6 (worthlessness) and PHQ2 (depressed or sad mood). PHQ4 (fatigue) was also the most key bridge symptom liking depression and pain, followed by PHQ3 (sleep difficulties). There were no significant differences in network global strength (females: 4.36 vs. males: 4.29; S = 0.075, P = 0.427), network structure-distribution of edge weights (M = 0.12, P = 0.541), and individual edge weights between male and female participants. Conclusion: Depressive and pain symptoms showed strong cross-association with each other. "Fatigue" was the strongest central and bridge symptom in the network model, while "sleep difficulties" was the second strongest bridge symptom. Targeting treatment of both fatigue and sleep problems may help improve depressive and pain symptoms in those affected.

Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial. METHODS: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102). FINDINGS: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups. INTERPRETATION: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients. FUNDING: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.

Bullying, Present Romantic Relationship and Depression as Predictive Factors of Non-Suicidal Self-Injury in Adolescent Psychiatric Patients (preprint)

Background: Non-suicidal self-injury (NSSI), as a major public health issue of high complexity, multifactorial causes and great socioeconomic and family impact, affects China now especially after COVID-19. The aim of this study was to explore the clinical and psychological characteristic in adolescent psychiatric patients with or without NSSI. Methods: : Adolescent psychiatric patients were recruited from psychiatric outpatient and inpatient unit in Guangdong mental Health Center between October and December 2020. NSSI was evaluated by the modified version of Adolescents Self-Harm Scale. Childhood trauma was assessed by the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Peer bullying experience was evaluated by The Revised Olweus Bully/Victim Questionnaire（BVQ-R). Depression was assessed by the Montgomery–Asberg Depression Rating Scale (MADRS). Clinical data were collected from electronic medical record system. Results: : The sample included 157 adolescent psychiatric patients (72.6% female), aged 13-18 years (M=15.39, SD=0.145). NSSI group experienced more peer bullying (t=4.08, P ＜0.001), more likely to get into romantic relationship currently(χ2=5.38, P =0.02), more times of hospitalization (t=0.36, P <0.001), receiving more antipsychotic treatment (t=3.58, P <0.001), benzodiazepine treatment (t=3.46, P ＜0.001), and mood-stabilizer treatment (χ2 =8.53, P <0.001). The significant predictor of NSSI for the last one year included being in romantic relationship currently (OR =4.27, 95% CI=[1.53,11.93]), outpatient (OR=0.38, 95%CI=[0.16,0.88]), BVQ-R total (OR=1.10, 95% CI=[1.02,1.18])，MARDS total (OR= 1.05, 95% CI=[1.01,1.09]), and benzodiazepine PDD/DDD (OR=5.79, 95% CI=[0.99,33.72]). Conclusions: : Adolescent psychiatric patients with NSSI have significantly higher incidences of life event such as peer bulling, childhood trauma experience, and they were more likely to get into a romantic relationship. Meanwhile, patients with NSSI had significantly severe level of depression, being more on benzodiazepine and mood-stabilizer use. This provides a valuable basis for our clinical treatment of adolescent mental patients with NSSI.

Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. METHODS: We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. RESULTS: A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67-100%), 82.72% (95% CI: 78.19-86.81%), 53.02% (45.28-60.68%), and 14.16% (95% CI: 8.4-21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73-63.87%), 55.23% (95% CI: 50.22-60.19%), 27.07% (95% CI: 19.87-34.93%), 46.37% (95% CI: 39.97-52.83%), 28.87% (95% CI: 22.76-35.40%), 28.75% (95% CI: 21.46-36.64%), 17.32% (95% CI: 15.44-19.29%), and 36.19% (95% CI: 21.90-51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Remote Human-robot Collaborative Impedance Control Strategy of Pharyngeal Swab Sampling Robot

Pharyngeal swab sampling, as an essential link in the detection of COVID-19, is characterized by the large task volume and susceptibility to infection. Therefore, it is necessary to use medical robots for remote sampling instead of in-situ sampling. However, on one hand, due to the influence of network delay, it is difficult to guarantee the closed-loop performance manipulated remotely by medical practitioners. On the other hand, the sampling process controlled by the robot independently is not always successful due to the inaccuracy of the planned trajectory caused by the sensors or the moment of the patients. To solve the problems discussed above, this paper proposed a remote human-robot collaborative strategy based on impedance control method, which can integrate the experience of medical practitioners into the automatic sampling process. During the sampling process, when the inaccurate scanning trajectory is detected, the medical practitioners can correct the planned trajectory on line according to the sensor information and the reaction of the patients. Then, the cooperative robot tracks the adjusted planned-trajectory based on the impedance control method and ensure that the contact force of sampling is maintained within a reasonable range. The simulation results show that the proposed human-robot collaborative strategy is effective taking the advantages of both medical practitioners and robots which can deal with the trajectory tracking problem caused by the inaccurate sampling of patients. © 2020 IEEE.

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.

How to evaluate the value of chest CT in COVID-19: case reports and literature review.

The coronavirus disease 2019 (COVID-19) that occurred in Wuhan, Hubei Province, China, has been declared a public health emergency of international concern and a pandemic by the World Health Organization. The Chinese government has temporarily taken strong response measures and effective procedures to stop the further expansion and development of the epidemic. It is important for clinicians to screen, diagnose, and monitor COVID-19.

The value of serum amyloid A for predicting the severity and recovery of COVID-19.

The present study aimed to evaluate the value of serum amyloid A (SAA) in coronavirus disease 2019 (COVID-19) and compared the efficacy of SAA and C-reactive protein (CRP) in predicting the severity and recovery of COVID-19. A retrospective study was conducted on COVID-19 patients hospitalized in Wuhan No. 1 Hospital (Hubei, China) from January 21, 2020 to March 4, 2020. A two-way ANOVA analysis was used to compare the serum CRP and SAA levels between mild group and severe group during hospitalization days. Linear regression was used to analyze the relationship between the serum CRP, SAA levels and treatment days in recovered patients. The Logistic regression analysis and the area under curve (AUC) were calculated to determine the probability for predicting the severity and recovery of COVID-19. The severe group displayed higher CRP and SAA levels compared with the mild group during hospitalization (P<0.001). Logistic regression indicated that SAA and CRP were independent risk factors for the severity of COVID-19. The corresponding AUC of CRP and SAA values for severity of COVID-19 were 0.804 and 0.818, respectively. Linear regression analysis revealed that CRP and SAA levels were negatively correlated with treatment days in recovered patients (r=-0.761, -0.795, respectively). Logistic regression demonstrated that SAA was an independent factor for predicting the recovery of COVID-19. However, CRP could not predict the recovery of COVID-19. The corresponding AUC of SAA for the recovery of COVID-19 was 0.923. The results of the present study indicated that SAA can be considered to be a biomarker for predicting the severity and recovery of COVID-19.

Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.

Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.

Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak.

The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.