Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells.

BACKGROUND: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. METHODS: We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. RESULTS: Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025). CONCLUSIONS: Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.

Factors associated with the time to return negative RT-PCR from COVID-19 in paediatric patients: a retrospective cohort study.

OBJECTIVE: This study aimed to describe the epidemiological and clinical features and potential factors related to the time to return negative reverse transcriptase (RT)-PCR in discharged paediatric patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Unscheduled admissions to 12 tertiary hospitals in China. PARTICIPANTS: Two hundred and thirty-three clinical charts of paediatric patients with confirmed diagnosis of COVID-19 admitted from 1 January 2020 to 17 April 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures: factors associated with the time to return negative RT-PCR from COVID-19 in paediatric patients. SECONDARY OUTCOME MEASURES: epidemiological and clinical features and laboratory results in paediatric patients. RESULTS: The median age of patients in our cohort was 7.50 (IQR: 2.92-12.17) years, and 133 (57.1%) patients were male. 42 (18.0%) patients were evaluated as asymptomatic, while 162 (69.5%) and 25 (10.7%) patients were classified as mild or moderate, respectively. In Cox regression analysis, longer time to negative RT-PCR was associated with the presence of confirmed infection in family members (HR (95% CI): 0.56 (0.41 to 0.79)). Paediatric patients with emesis symptom had a longer time to return negative (HR (95% CI): 0.33 (0.14 to 0.78)). During hospitalisation, the use of traditional Chinese medicine (TCM) and antiviral drugs at the same time is less conducive to return negative than antiviral drugs alone (HR (95% CI): 0.85 (0.64 to 1.13)). CONCLUSIONS: The mode of transmission might be a critical factor determining the disease severity of COVID-19. Patients with emesis symptom, complications or confirmed infection in family members may have longer healing time than others. However, there were no significant favourable effects from TCM when the patients have received antiviral treatment.

Can Clinical Symptoms and Laboratory Results Predict CT Abnormality? Initial Findings Using Novel Machine Learning Techniques in Children With COVID-19 Infections.

The rapid spread of coronavirus 2019 disease (COVID-19) has manifested a global public health crisis, and chest CT has been proven to be a powerful tool for screening, triage, evaluation and prognosis in COVID-19 patients. However, CT is not only costly but also associated with an increased incidence of cancer, in particular for children. This study will question whether clinical symptoms and laboratory results can predict the CT outcomes for the pediatric patients with positive RT-PCR testing results in order to determine the necessity of CT for such a vulnerable group. Clinical data were collected from 244 consecutive pediatric patients (16 years of age and under) treated at Wuhan Children's Hospital with positive RT-PCR testing, and the chest CT were performed within 3 days of clinical data collection, from January 21 to March 8, 2020. This study was approved by the local ethics committee of Wuhan Children's Hospital. Advanced decision tree based machine learning models were developed for the prediction of CT outcomes. Results have shown that age, lymphocyte, neutrophils, ferritin and C-reactive protein are the most related clinical indicators for predicting CT outcomes for pediatric patients with positive RT-PCR testing. Our decision support system has managed to achieve an AUC of 0.84 with 0.82 accuracy and 0.84 sensitivity for predicting CT outcomes. Our model can effectively predict CT outcomes, and our findings have indicated that the use of CT should be reconsidered for pediatric patients, as it may not be indispensable.

Comparison of clinical features on admission between coronavirus disease 2019 and influenza a among children: a retrospective study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) share similar symptoms with influenza A (IA), but it is more worthwhile to understand the disparities of the two infections regarding their clinical characteristics on admission. METHODS: A total of 71 age-matched pediatric IA and COVID-19 patient pairs were formed and their clinical data on admission were compared. RESULTS: Fever, cough, nasal congestion and nausea/vomiting were the most common symptoms on admission for both infections but occurred less often in COVID-19. The IA patients were more likely to have lower-than-normal levels of lymphocyte count and percentage and to have higher-than-normal levels of activated partial thromboplastin time, prothrombin time, serum C-reactive protein, and serum procalcitonin, while the COVID-19 patients had higher odds of having lower-than-normal levels of neutrophil count and percentage. CONCLUSIONS: This study suggests that influenza A is more symptomatic than COVID-19 for children and might be an overall more severe infection at the time of admission.

Clinical features and follow-up of pediatric patients hospitalized for COVID-19.

OBJECTIVE: This report summarizes the clinical features and 1-month follow-up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID-19) in Wuhan Women and Children's Hospital. METHODS: The 1-month follow-up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM tests, reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, lung computed tomography (CT) scans, and laboratory tests. RESULTS: Between January 20 and March 15, 2020, 127 patients aged 0-15 years were hospitalized for COVID-19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon-α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band  (CK-MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 109 /L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%-37%) of patients and persistently elevated serum creatine kinase and CK-MB levels. The median duration of elevated CK-MB was 45 days. The mean concentrations of serum SARS-CoV-2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow-up, four patients retested positive for SARS-CoV-2. CONCLUSIONS: The involvement of different lung lobes in patients with COVID-19 was associated with variations in the persistence of pneumonia and elevation of CK-MB levels and body temperature.

Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development. METHODS: This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age. RESULTS: Of 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates. CONCLUSIONS: Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.

Effects of SARS-CoV-2 infection on neuroimaging and neurobehavior in neonates.

BACKGROUND: We collected neonatal neurological, clinical, and imaging data to study the neurological manifestations and imaging characteristics of neonates with coronavirus disease 2019 (COVID-19). METHODS: This case-control study included newborns diagnosed with COVID-19 in Wuhan, China from January 2020 to July 2020. All included newborns had complete neurological evaluations and head magnetic resonance imaging. We normalized the extracted T2-weighted imaging data to a standard neonate template space, and segmented them into gray matter, white matter, and cerebrospinal fluid. The comparison of gray matter volume was conducted between the two groups. RESULTS: A total of five neonates with COVID-19 were included in this study. The median reflex scores were 2 points lower in the infected group than in the control group (P = 0.0094), and the median orientation and behavior scores were 2.5 points lower in the infected group than in the control group (P = 0.0008). There were also significant differences between the two groups in the total scale score (P = 0.0426). The caudate nucleus, parahippocampal gyrus, and thalamus had the strongest correlations with the Hammersmith neonatal neurologic examination (HNNE) score, and the absolute correlation coefficients between the gray matter volumes and each part of the HNNE score were all almost greater than 0.5. CONCLUSIONS: We first compared the neurological performance of neonates with and without COVID-19 by quantitative neuroimaging and neurological examination methods. Considering the limited numbers of patients, more studies focusing on the structural or functional aspects of the virus in the central nervous system in different age groups will be carried out in the future.

Association between vaccinations and clinical manifestations in children with COVID-19.

BACKGROUND: The infection rate of Coronavirus Disease 2019 (COVID-19) in children was less than that in adults. However, the underlining reason is not well known. METHODS: Children with COVID-19 were recruited from two Children's Hospitals in Wuhan and Shanghai in this case-control study. The associations of initial symptoms with age, vaccinations of Bacillus Calmette Guerin (BCG), and influenza and pathogens were determined by Chi-square t-test. RESULTS: We evaluated 248 confirmed cases, and 56 suspected cases with COVID-19. The median age was 6.82 years old, and 118 cases (38.82%) were girls. Furthermore, 30.26% of all patients were asymptomatic cases. The percentage of asymptomatic cases vaccinated with BCG was not significantly higher than that without BCG vaccination [86/280 (30.71%) vs. 6/13 (46.15%), P=0.203], and initial symptoms were not related with immunized influenza vaccine (P=0.267). Compared to parameters in pediatric patients with normal body temperatures, patients with fever had higher C reactive protein (CRP) (P<0.001). CONCLUSIONS: Pediatric COVID-19 patients with BCG vaccinations exhibit similar clinical manifestations compared to those without BCG vaccinations, and the severity of symptoms in pediatric patients may be related to the maturity of immune function.

Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.

Introduction: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin-converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 15, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children's lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Results: It revealed that infants (< 1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (> 1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children's lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants' lungs. The ACE2+SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Conclusions: Infants (< 1 yrs.-old) with SARS-CoV-2 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from SARS-CoV-2 infection.

Comparative analysis of clinical features of SARS-CoV-2 and adenovirus infection among children.

BACKGROUND: The new emerging coronavirus disease 2019 (COVID-19) overall shares similar symptoms with other common respiratory viral infections. We aimed in this study to compare COVID-19 and human adenovirus (HAdV) infections in pediatric patients regarding the frequencies of major clinical symptoms and the potential disparities in laboratory and imaging parameters. METHODS: Following a case-control-like design, we built 72 age-matched pediatric COVID-19 and HAdV patient pairs. Their early symptoms and laboratory and imaging characteristics were then retrieved and compared. RESULTS: Fever and cough were the most common symptoms for both infections but were seen more often in HAdV than in COVID-19 patients (92% vs. 66% and 60% vs. 18%, respectively). Compared with COVID-19 patients, children with HAdV infection had statistically significantly higher values of neutrophil count, neutrophil percentage, activated partial thromboplastin time, prothrombin time, lactate dehydrogenase, C-reactive protein, procalcitonin but lower values of lymphocyte percentage, total bilirubin, potassium and sodium. Thoracic computed tomography also revealed more anomalies in HAdV patients than in COVID-19 patients (95% vs. 67%). CONCLUSIONS: COVID-19 is an overall less symptomatic and less severe infection at admission compared to HAdV respiratory infection in pediatric population.

Features Discriminating COVID-19 From Community-Acquired Pneumonia in Pediatric Patients.

Purpose: To discuss the different characteristics of clinical, laboratory and chest computed tomography (CT) between coronavirus disease 2019 (COVID-19) and community-acquired pneumonia (CAP) in pediatric patients. Methods: We retrospectively retrieved data of inpatients with COVID-19 from January 21st to March 14th, 2020, and CAP from November 1st, 2019 to December 31st, 2019 in Wuhan Children's Hospital. We divided CAP into mycoplasma pneumonia and other viral pneumonia. We analyzed clinical and radiological features from those patients, and compared the differences among COVID-19, mycoplasma pneumonia and other viral pneumonia. Results: Eighty COVID-19 inpatients from January 21st to March 14th, 2020, as well as 95 inpatients with mycoplasma pneumonia and 50 inpatients with other viral pneumonia from November 1st, 2019 to December 31st, 2019 were included in our study. All patients were confirmed with RT-PCR. The clinical symptoms were similar in the three groups. Except fever and cough, diarrhea (6/80, 7.5%), tachypnea (2/80, 2.5%), and fatigue (6/80, 7.5%) were less common in COVID-19 patients. Compared to mycoplasma pneumonia and other viral pneumonia inpatients, COVID-19 patients present remarkably increased alanine aminotransferase (69/80, 86.3%). The typical CT feature of COVID-19 is ground-glass opacity, and it was more common in COVID-19 patients (32/80, 40%). Conclusion: The COVID-19 shared similar onsets with CAP. Even though the ground-glass opacity and elevated level of ALT were frequent in COVID-19, the better way for treatment and management of this disease is quickly and accurately identifying the pathogen.

Clinical Features and Temporal Changes of RT-PCR and Chest CT in COVID-19 Pediatric Patients.

Objective: This work aims to investigate the clinical features and the temporal changes of RT-PCR and CT in COVID-19 pediatric patients. Methods: The clinical, RT-PCR, and CT features of 114 COVID-19 pediatric in-patients were retrospectively reviewed from January 21 to March 14, 2020. All patients had chest CT on admission and were identified as positive by pharyngeal swab nucleic acid test. The clinical features were analyzed, as well as the features and the temporal changes of RT-PCR and CT. Results: Fever (62, 54%) and cough (61, 54%) were the most common symptoms. There were 34 (30%) cases of concurrent infections. The most common imaging features on CT were ground-glass opacities (46, 40%) and consolidation (46, 40%). The bilateral lower lobes were the most common pattern of involvement, with 63 cases (55%) involving one to two lobes, and in 32 (28%) cases CT was normal. Throughout the whole duration of COVID-19 in children, the diagnostic positive rate of RT-PCR has been far higher than that of CT (all P < 0.05). For RT-PCR follow-up, reliable negative results were obtained only 7 days after the onset of symptoms. Though lung involvement on chest CT progressed rapidly in several cases, lung involvement in children with COVID-19 is mild, with a median value of 2 on CT score. Conclusions: RT-PCR is more reliable than CT in the initial diagnosis of pediatric patients with COVID-19. On follow-up, reliable negative RT-PCR results are available 7 days after the initial symptoms. The use of CT should be considered for follow-up purposes only if necessary.

Overview of chest involvement at computed tomography in children with coronavirus disease 2019 (COVID-19).

BACKGROUND: Chest computed tomography (CT) findings in children with coronavirus disease 2019 (COVID-19) have been rarely reported in a comprehensive and systematic manner. OBJECTIVE: We investigated the chest CT findings in children with COVID-19, and explored the differences in these findings between symptomatic patients and asymptomatic patients. MATERIALS AND METHODS: Demographic findings, clinical characteristics, duration of hospital stay and viral shedding, and chest CT findings in 201 children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were retrospectively analyzed from January 15 to March 20, 2020, and divided into two groups: symptomatic group (n=136) and asymptomatic group (n=65). Chi-square test and Student's t-test were used for statistical analysis. RESULTS: Symptomatic patients were mainly young children ≤3 years old (54/63, 86%),while asymptomatic patients were mainly children ≥ 6 years old (51/111, 46%). Fever (41%) and cough (41%) were the most common symptoms. Overall, 119/201 (59%) patients had chest CT findings, and symptomatic patients accounted for 82% (98/119). The CT findings presented as bilateral multiple lesions (60/119, 50.4%), ground-glass opacities (83/119, 70%) and/or consolidation (44/119, 37%) with a peripheral and subpleural distribution (62/83, 75%). Fifteen of 87 (7.2%) patients with lung lesions showed complete lesion absorption, and 42/87 (48%) improved within a mean of 9.1 (standard deviation [SD] 3.2) days. The mean duration of viral shedding was 8.7 (SD 4.9) days. Pleural effusion was very rare. No lymphadenopathy was found in either group. CONCLUSION: Symptoms associated with pulmonary involvement were most common in infants and young children. The lung lesions of most patients were absorbed and improved in about 9 days.

Association of Web-Based Physical Education With Mental Health of College Students in Wuhan During the COVID-19 Outbreak: Cross-Sectional Survey Study.

BACKGROUND: The COVID-19 outbreak has affected people's health worldwide. For college students, web-based physical education is a challenge, as these course are normally offered outdoors. OBJECTIVE: The aim of this study was to use data from a web-based survey to evaluate the relationship between the mental health status of college students and their sports-related lifestyles. Problems related to web-based physical education were also examined. METHODS: A web-based survey was conducted by snowball sampling from May 8 to 11, 2020. Demographic data, mental health status, and sports-related lifestyles of college students in Wuhan as well as issues related to web-based physical education were collected. Mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: The study included 1607 respondents from 267 cities. The average scores of the DASS-21 subscales (2.46 for depression, 1.48 for anxiety, and 2.59 for stress) were significantly lower in our study than in a previous study (P<.05). Lower DASS-21 scores were significantly correlated with regular exercise, maintaining exercise habits during the outbreak of COVID-19, exercising more than 1 to 2 times a week, exercise duration >1 hour, and >2000 pedometer steps (all P<.05). None of the three forms of web-based physical education was preferred by more than 50% of respondents. Frequent technical problems were confronted by 1087/1607 students (67.6%). Shape-up exercises (846/1607, 52.6%), a designed combination of exercises (710/1607, 44.2%), and Chinese kung fu (559/1607, 34.8%) were suggested sports for web-based physical education. CONCLUSIONS: Mental status was significantly correlated with regular exercise and sufficient exercise duration. Professional physical guidance is needed for college students in selected sports. Exercises not meeting students' preferences, frequent technical problems, and the distant interaction involved in web-based physical education were the main problems that should be solved in future.

Intussusception in 2 Children With Severe Acute Respiratory Syndrome Coronavirus-2 Infection.

We note that intussusception was likely associated with severe acute respiratory syndrome coronavirus-2 infection in 2 infants in Wuhan and London. The intussusception was reduced by enemas in Wuhan; the outcome was fatal. The intussusception was not reduced by enemas in London and required surgery; the outcome was favorable.