Correction: SARS-CoV-2 infection in China-Before the pandemic.

[This corrects the article DOI: 10.1371/journal.pntd.0008472.].

A proposed artificial intelligence workflow to address application challenges leveraged on algorithm uncertainty.

Artificial Intelligence (AI) has achieved state-of-the-art performance in medical imaging. However, most algorithms focused exclusively on improving the accuracy of classification while neglecting the major challenges in a real-world application. The opacity of algorithms prevents users from knowing when the algorithms might fail. And the natural gap between training datasets and the in-reality data may lead to unexpected AI system malfunction. Knowing the underlying uncertainty is essential for improving system reliability. Therefore, we developed a COVID-19 AI system, utilizing a Bayesian neural network to calculate uncertainties in classification and reliability intervals of datasets. Validated with four multi-region datasets simulating different scenarios, our approach was proved to be effective to suggest the system failing possibility and give the decision power to human experts in time. Leveraging on the complementary strengths of AI and health professionals, our present method has the potential to improve the practicability of AI systems in clinical application.

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.

Association Between the COVID-19 Pandemic and Infant Neurodevelopment: A Comparison Before and During COVID-19.

Aim: To investigate the association between the experience of the coronavirus disease 2019 (COVID-19) pandemic and neurodevelopment of 6-month-old and 1-year-old children and explore the differences in the association by birth order. Methods: This comparison study was embedded in the Born in Guangzhou Cohort Study in China. The exposed group included 546 6-month-old and 285 1-year-old children who attended neurodevelopment assessments between March 1 and May 15, 2020, and the non-exposed group included 3,009 6-month-old and 2,214 1-year-old children during the same months from 2015 to 2019. Neurodevelopment at age 6 months and 1 year was assessed by trained clinical staff using the Ages and Stages Questionnaires, third edition (ASQ-3) and the Gesell Developmental Schedules (GDS). Results: The experience of the pandemic in 2020 was associated with a higher risk of delay in the fine motor (adjusted OR: 2.50, 95% CI: 1.25, 4.99; estimated by logistic regression) and communication (adjusted RR [aRR]: 1.13, 95% CI: 1.02, 1.25; estimated by log-binomial regression) domains at age 1 year. The association between the experience of the pandemic and communication delay at age 1 year only existed in first-born children (aRR: 1.15, 95% CI: 1.03, 1.30) but not in later-born children (aRR: 1.02, 95% CI: 0.84, 1.25). No associations were observed in any domain among 6-month-olds. Conclusion: Experiencing the COVID-19 pandemic and related public health strategies might be associated with a higher risk of delay in the development of fine motor and communication in 1-year-old children; the association observed in the communication domain only existed in first-born children.

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 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.

SARS-CoV-2 infection in China-Before the pandemic.

In order to rapidly inform polices in the international response to the ongoing pandemic of coronavirus disease 19 (COVID-19), we summarize in this review current evidence on epidemiological and clinical features of the infection, transmission routes, problems of nucleic-acid testing, the epidemiological trend in China and impact of interventional measures, and some lessons learned. We concluded that the epidemic is containable with traditional nonpharmacological interventions, mainly through social distancing and finding and isolating suspected patients and close contacts. Nonpharmacological interventions are the only effective measures currently accessible and have suppressed some 90% of the infections in China. Close contacts are the major mechanism of transmission, which makes it possible to control this epidemic through nonpharmacological methods. Nucleic-acid testing alone may miss some 50% of infected patients, and other methods such as chest computerized tomography (CT) or serology should be considered to supplement molecular testing. The development of vaccines and drugs is important, but hesitation to make use of nonpharmacological interventions may mean missing golden opportunities for effective actions.

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.

We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal-oral transmission.