key: cord-1031521-q5a86i8x authors: Yang, Rongrong; Gui, Xien; Zhang, Yongxi; Xiong, Yong title: The challenge of resuming classes for young students in Wuhan, China date: 2020-05-06 journal: Expert Rev Respir Med DOI: 10.1080/17476348.2020.1761792 sha: 7f8c18784bbcbc7f1c0a9fa410f6bd10060216fc doc_id: 1031521 cord_uid: q5a86i8x nan COVID-19 pneumonia is a newly recognized illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world [1] [2] [3] . While swift isolation of individuals COVID-19 is at the core of the epidemic response of virtually all countries worldwide, it is likely that some asymptomatic patients, defined as those who do not show any relevant clinical symptoms, such as fever, cough, sore throat, and other self-perceived or clinically recognizable symptoms, but whose respiratory tract specimens test positive for COVID-19, are not captured in the established surveillance systems. Under the strict control of the Chinese government, Wuhan has had no new COVID-19 cases for several days since 18 March 2020, when both the new COVID-19 suspected cases and inventory COVID-19 suspected cases reduced to zero [4] . However, the spread of COVID-19 has not been effectively controlled in many other countries. As of April 17, in Wuhan, apart from the normal winter vacation, more than 2 months have passed since the regular date of resuming classes. When students can safely resume classes is a reference standard to evaluate the degree of threat to public health and to measure the effectiveness of controlling COVID-19 in China and around the world. As the first epicenter, Wuhan had the largest number of cases and potentially infected children in China, and their children have experienced the longest school closure in the world thus far. As more and more countries have closed their schools in facing COVID-19, the question of resuming classes for young children is relevant and important for not only Wuhan but also most countries affected by COVID-19. By analyzing the challenges of resuming school for children in Wuhan and targeted strategies, the original intention of this paper is to provide valuable experience for all children affected by the prevalence of COVID-19 all over the world. Asymptomatic COVID-19 infections were previously reported in children [5] [6] [7] . One report about a familial cluster of COVID-19 found a 10-year-old boy had a positive result on qRT-PCR for COVID-19 and had ground-glass lung opacities identified by CT scan, whereas none clinical symptoms were observed during the whole hospitalization [5] . This study indicated that asymptomatic COVID-19 infection was possible. In another family cluster, three individuals were tested positive for COVID-19 infection on qRT-PCR, but two were asymptomatic patients [6] . This study hinted that asymptomatic COVID-19 patients might be overlooked by health-care professionals and thus unknowingly transmit the virus to others. On the basis of two reports on family cluster with COVID-19 infection (Family 1 and Family 2 shown in Table 1 ) [5, 6] , here, we reported another family cluster with COVID-19 asymptomatic infection (Family 3 shown in Table 1 ). The father, a 38-year-old man, was a doctor working in a designated COVID-19 hospital since 21 January 2020. On Feb 10, he developed a fever of 37.8°C. Considering the COVID-19 outbreak and several colleagues had been infected with COVID-19, he underwent a series of tests related to COVID-19. The reports showed that he had a decreased lymphocyte count, abnormal chest CT images, and a positive result on qRT-PCR for COVID-19. The next day, as close contacts, his wife, his twins son and daughter were also screened for COVID-19. By contrast, they were all asymptomatic, with normal lymphocyte counts. All the serological indicators are shown in Table 2 . The difference is that the wife and 7-year-old daughter had normal chest CT images but positive qRT-PCR for COVID-19, while the 7-year-old son had negative qRT-PCR for 4 times, but chest CT images showed typical findings-multiple patchy ground-glass shadows (Figure 1(a) ). It is interesting that the son had alanine aminotransferase (ALT) as high as 520 U/L and aspartate aminotransferase (AST) as high as 439 U/L when he was admitted to hospital on Feb 13. To identify the cause of liver damage, common etiological tests, including hepatitis a virus, hepatitis b virus, hepatitis c virus, hepatitis e virus, and EB virus, were all negative. Moreover, the child had not taken any medicine before the testing, including over the counter Chinese medicine. The oral Diammonium glycyrrhizinate enteric capsule was then taken to repair liver damage. During the period of isolation, an obvious process of changes on liver function tests of the son had been shown (Table 3 ). Throughout the course of the disease, the 7-year-old boy had a completely normal appetite. During the observation period from February 10 to February 29, the wife, the twins son and daughter in Family 3 still did not show any symptoms. The wife and the daughter both had negative qRT-PCR for COVID-19 on Feb 20 and Feb 17 ( (Table 4 ), but chest CT images showed that the lung lesions were basically absorbed and slight fibrosis were occurred (Figure 1(b) ). The above three different families show a common characteristic. That is, throughout the course of COVID-19 infection, the children did not have any clinical symptoms. There is accumulating evidence indicating that a substantial fraction of COVID-19-infected individuals are asymptomatic [8] [9] [10] [11] [12] , especially in children aged 0-14 years [5] [6] [7] 13] . The estimated asymptomatic proportion were 17.9% [9] and 16.7% [10] in two studies, respectively. Considering the reported similarity in viral loads between asymptomatic and symptomatic patients [14] and that transmission of COVID-19 by asymptomatic cases may be possible. Later, a study on a familial cluster of five patients with COVID-19 infection in Anyang, China, confirmed that the coronavirus may have been transmitted by the asymptomatic carrier [15] . Another epidemiological study found that COVID-19 infection rates among close contacts of asymptomatic and symptomatic COVID-19 patients were 4.11% (6/146) and 6.3% (126/2001), respectively, which showed no statistical difference [10] . A recent research pointed out that substantial undocumented infection facilitates the rapid dissemination of COVID-19 [16] . In preparation for the resumption of classes, the contagious of COVID-19 asymptomatic infection children should be paid special attention to avoid second outbreak of the disease. Moreover, there are some clues but inconclusive findings about the characteristics of asymptomatic COVID-19 infection children. Such as the 7-year-old boy in Family 3, although it was not clear that the liver damage in this child was caused by COVID-19 infection, the possibility cannot be ruled out at least. Liver damage has been reported in symptomatic COVID-19 patients [17] [18] [19] [20] , but such severe and reversible liver damage in asymptomatic patients has not been reported. In addition, COVID-19 can bind to their target cells through angiotensinconverting enzyme 2 (ACE2), which can be expressed by testis [21] [22] [23] . Whether this theoretical combination of virus and target cells affects testicular function is still unknown and needs further investigation. In view of the occult, infectious, disease diversity, and uncertainty damage to testis of COVID-19 asymptomatic infected children, the safe time of resuming classes in highincidence areas must be carefully evaluated. Otherwise, once an outbreak occurs in schools where the population is concentrated, it will spread much faster than in communities. How to avoid the resumption of classes leading to the second epidemic outbreak of COVID-19 is an urgent problem to be solved. In our opinion, the next stage of COVID-19 prevention and control needs to focus on the screening of asymptomatic population in the community. Before the school is ready to resume classes, children should be closely monitored and examined for nucleic acid testing of COVID-19 to rule out asymptomatic infection, even if they do not have any symptoms. There is no doubt that the economic cost of COVID-19 screening is considerable. Different countries may need to further balance the input-output ratio according to their national conditions. There were some limitations in this study. First, the 7-year-old boy in Family 3 presented with typical viral pneumonia, but the cause of the negative results of viral nucleic acid is unclear. The possibility of poor technique of nasopharyngeal swab collection and PCR detection for SARS-CoV-2 nucleic acid are excluded, because his sister and mother were operated by the same nurse and laboratory technician. It is also unlikely that the boy was infected with mutated SARS-CoV-2, because his sister, his mother, and he were all close contacts with his father. The low sensitivity of the test reagent may be the reason for the negative result, so it is necessary to improve the sensitivity of the test kit. Second, alternative samples for detection of SARS-CoV-2 (such as stool) were not collected as medical resources are extremely limited at the early stage of COVID-19 outbreak in Wuhan. Simultaneous testing of multiple samples may be an effective measure to decrease the occurrence of false-negative results. Moreover, repeated testing of lower respiratory tract samples are warranted in clinically suspected cases with an initially negative result in nasopharyngeal swab. Based on our data on SARS-CoV-2 RNA shedding in stool and the possibility of a lag in viral detection in nasopharyngeal swab specimens, the assessment of both fecal and respiratory specimen is recommended to enhance diagnostic sensitivity, and also to aid discharge decision before the role of viral RNA shedding in stool is clarified. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. RY conceived the study. RY and YX wrote the protocol. YZ performed the literature search. RY and YZ performed the statistics and drafted the first manuscript. XG and YX critically revised the manuscript. All authors reviewed and approved the final manuscript. A novel coronavirus from patients with pneumonia in China Clinical features of patients infected with 2019 novel coronavirus in Wuhan First case of 2019 novel coronavirus in the United States • The report about the first case of COVID-19 in United States. 4. 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