key: cord-0703421-9kf3v8af authors: Xie, Zhengde title: Pay attention to SARS‐CoV‐2 infection in children date: 2020-03-17 journal: Pediatr Investig DOI: 10.1002/ped4.12178 sha: 405175db3c20b8eacd8b0d824277035aa448cae9 doc_id: 703421 cord_uid: 9kf3v8af nan The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been prevalent for nearly two months. The first case of COVID-19 was reported in Wuhan, Hubei Province, China in mid-December, 2019. On January 9, 2020, Chinese scientists isolated and obtained the genome sequence of the new virus; they shared the genome information on relevant international websites one day later. 1, 2 Announcement No. 1 of the National Health Commission of the People's Republic of China (on January 20, 2020) has categorized COVID-19 as a Class B infectious disease, in accordance with the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases; however, the announcement urged public health authorities to undertake prevention and control appropriate for a Class A infectious disease. 3 As of January 31, 2020, there were 9720 confirmed cases of COVID-19 in China and a total of 9826 cases have been reported globally, involving 19 countries. WHO declared the outbreak to be a public health emergency of international concern on January 31 2020. 4 Thus far, the SARS-CoV-2 outbreak has not been well controlled and requires close attention. Coronavirus (CoV) belongs to the family Coronavirinae of the order Nidovirales. Based on analysis of their genomic structure and phylogenetics, CoVs are divided into four genera: α, β, γ, and δ. Both α and β CoVs only infect mammals, whereas γ and δ CoVs mainly infect birds and rarely infect mammals. The genome of CoV is a complete C o m m e n t a r y This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. single-stranded positive-sense RNA of approximately 30 kb in length, which is the largest of all RNA viruses. It also exhibits typical characteristics of RNA viruses, including a 5' cap and 3' poly-A tail. 5, 6 Based on currently available evidence, CoVs infecting humans include two α-CoVs (229E and NL63), and five β-CoVs (OC43, HKU1, Middle East respiratory syndrome coronavirus [MERS-CoV], severe acute respiratory syndrome coronavirus [SARS-CoV], and SARS-CoV-2). 5 SARS-CoV-2 is a new species of the β-coronavirus genera, which includes bat-SARS-like (SL)-CoV ZC45, bat-SL-CoV ZXC21, SARS-CoV, and, MERS-CoV. Phylogenetic analysis showed that SARS-CoV-2 is more closely related to bat-SL-CoV ZC45 and bat-SL-CoV ZXC21, whereas it is distantly related to SARS-CoV. 7 Current research has shown that SARS-CoV-2 came from wild animals, although its specific source requires further investigations. 5, 7 The currently reported cases of COVID-19 mainly occurred in adults, and there have been no large-scale studies of their clinical features. 8 ). Thirteen (32%) patients were admitted to an ICU and six (15%) died. Notably, the proportion of critically ill patients and the case-fatality rate might have been biased in this report by Huang et al 8 due to its small sample size. SARS-CoV-2 is a newly emerged virus that may have originated from wild animals, and further indepth basic, clinical, and epidemiological research is necessary to identify and clarify its source, intermediate hosts, transmission routes and infectivity, susceptible populations, pathogenicity, and mortality. Thus far, a notable feature is that only a small number of confirmed cases of SARS-CoV-2 infection have involved children. [10] [11] [12] Most patients with SARS-CoV-2 infection are middle-aged and elderly individuals; the majorities of patients who were critically ill and patients who died comprised frail older adults and individuals with underlying diseases. Importantly, the proportion of children with SARS-CoV-2 infection has been low. The virus enters human alveolar epithelial cells by binding to receptors on the cell surface and then replicates by using cellular components. Current research findings suggest that the expression levels of angiotensin-converting enzyme 2 (i.e., ACE2), which may serve as the SARS-CoV-2 receptor, do not differ among age groups. 13 Therefore, children are presumably equally susceptible to infection with SARS-CoV-2. Possible explanations for the lower rate of SARS-CoV-2 infections in children are as follows: a) children are less likely to be exposed to the virus, due to their daily activities; and b) pediatric patients did not undergo laboratory tests because of mild symptoms, leading to fewer laboratory-confirmed cases. Further observations are needed to test these hypotheses. Another feature of SARS-CoV-2 infection in children is that their symptoms are mild or clinically absent. Importantly, cases of infection in children during the outbreaks of SARS-CoV in 2003 and MERS-CoV in 2012 were also characterized by low rates of infection, mild symptoms, and good prognosis. [14] [15] [16] Memish et al 15 summarized the clinical manifestations of disease in 11 pediatric patients who were diagnosed with MERS-CoV infection after close contact with infected family members. Two patients with underlying disease were symptomatic and the other nine patients were asymptomatic. No clinical manifestations were noted during 6 months of follow-up. The ability of a pathogen infection to cause severe illness and death mainly depends on the following factors: 1) Pathogenicity and virulence of the pathogen itself, which are the primary factors that determine whether a pathogen causes serious infection; for instance, Ebola virus and avian influenza A (H5N1) virus caused serious diseases in both children and adults. [17] [18] [19] 2) Genetic predisposition of the host. 3) Underlying disease and immune status of affected patients; for example, infants/young children and elderly patients are at high risk of infection with common respiratory viruses (e.g., influenza virus and respiratory syncytial virus) and are more likely to develop severe disease due to their relatively low/poor immune function and-particularly among elderly patients-the presence of underlying diseases. 20-22 4) Co-existing or secondary bacterial infections; for example, influenza co-infection with Streptococcus pneumoniae and Staphylococcus aureus can easily cause severe illness. 23,24 5) Accurate early diagnosis and rational treatment, which are important for prevention of critical illness; for example, early diagnosis of influenza and timely antiviral treatment within 48 hours of onset of symptoms can reduce the risk of severe illness. 25, 26 The causes of mild symptoms in children infected with SARS-CoV, MERS-CoV, or SARS-CoV-2 are unclear, and the following potential explanations require further research to determine their validity. The pathogenic mechanism of CoVs infection may be related to immune maturity; the immature immune system in children may prevent a strong response to some infections. For instance, primary Epstein-Barr virus (EBV) infection typically causes subclinical or mild disease in immunocompetent young children, but can cause typical infectious mononucleosis in older children, adolescents, and young adults. 27, 28 However, children are more susceptible than adults to infection with respiratory virus (including OC43, a β-CoV) and enterovirus; 29-32 they are also inoculated with a variety of antiviral vaccines in accordance with immunization schedules. As a result, there are multiple high-titer antibodies in the blood of children, which may offer cross-protection against SARS-CoV-2 infection. Because SARS-CoV-2 is an emerging virus, there is no specific antiviral treatment for the disease caused by this virus. Currently, the therapy of SARS-CoV-2 infection is symptomatic and supportive. Inhaled interferon-alpha and oral lopinavir/ritonavir are recommended as antiviral treatment by the National Health Committee of the People's Republic of China. Interferon-alpha may have potential benefits for patients infected with SARS-CoV-2, as it is a broad-spectrum antiviral drug. The efficacy and safety of lopinavir/ritonavir in the treatment of SARS-CoV-2 infection have not been supported by robust clinical evidence. For children with mild symptoms, lopinavir/ ritonavir treatment is not recommended. Overall, there remain many questions regarding SARS-CoV-2 infection, including its source, transmission pathway, and pathogenic mechanism, as well as humoral and cellular immune responses of infected patients, clinical features, populations at high risk, and prognosis of infected patients. The potential for SARS-CoV-2 infection in children is of particular concern. Further investigation and research are needed to explore the reasons for the fewer number of cases and the mild clinical manifestations in children with SARS-CoV-2 infection. Further monitoring and research are also necessary to determine whether SARS-CoV-2 will eventually cease to cause disease in humans, similar to the outcome of the SARS-CoV outbreak, or whether it will remain an important source of infectious disease. A novel coronavirus genome identified in a cluster of pneumonia cases -Wuhan A novel coronavirus from patients with pneumonia in China Novel coronavirus (2019-nCoV) situation report-11 Coronaviruses: genome structure, replication, and pathogenesis Epidemiology, genetic recombination, and pathogenesis of coronaviruses A pneumonia outbreak associated with a new coronavirus of probable bat origin Clinical features of patients infected with 2019 novel coronavirus in Wuhan Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Children's Hospital of Fudan University. Guideline on quick screening and clinical practice of children with suspected or confirmed 2019-nCoV infection/pneumonia Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement Study of clinical features and long-term outcomes of children's SARS cases Middle East respiratory syndrome coronavirus disease in children Middle East respiratory syndrome coronavirus disease is rare in children: An update from Saudi Arabia Comparison of epidemiological characteristics of human infection with avian influenza A (H5N1) virus in five countries of Asia and Africa Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: a systematic review of individual case data Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study Respiratory syncytial virus infection in adults Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza Insights into the interaction between influenza virus and pneumococcus Influenza and bacterial superinfection: Illuminating the immunologic mechanisms of disease Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-2010 influenza A (H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients Primary Epstein-Barr virus infection Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children Three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010 Detection and clinical analysis of acute lower respiratory tract infection with human coronaviruses in children in Beijing area 2007-2015 A novel human coronavirus OC43 genotype detected in mainland China Pediatric community-acquired pneumonia in the United States: Changing epidemiology, diagnostic and therapeutic challenges, and areas for future research How to cite this article: Xie Z. Pay attention to SARS-CoV-2 infection in children None.