key: cord-0751612-nbpd7l1j
authors: Cavalcante Pinto, Valdester; Moura, Luiz Francisco Wemmenson Gonçalves; Cavalcante, Rodrigo Cardoso; Rubens Costa Lima, José; Bezerra, Arnaldo Solheiro; de Sousa Dantas, Daylana Régia; Amaral, Cícero Matheus Lima; Lima, Daniel Freire; Viana, Antonio Brazil; Guedes, Maria Izabel Florindo
title: Prevalence of COVID-19 in children, adolescents, and adults in remote education situation in the city of Fortaleza – Brazil
date: 2021-05-01
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.04.086
sha: 05fec705ac13e7502e15a4912a342079c99d26aa
doc_id: 751612
cord_uid: nbpd7l1j

Objectives A retrospective study was conducted on a database of the COVID-19 Tracking Program in schoolchildren to identify the prevalence of COVID-19 through serology and RT-PCR in children, adolescents, and adults. Methods The data was composed of sociodemographic and clinical variables, results of serological tests (IgM and IgG), and RT-PCR results of IgM-positive individuals. The statistical analysis was performed with a 5% significance level. Results Among the 423 children, 107 (25.3%) exhibited seroprevalence, with IgG, IgM, or IgG/IgM. Among 854 adolescents, 250 (29.2%) had positive serology, and among 282 adults, 59 (20.9%) were positive. The frequency of positivity on RT-PCR for SARS-CoV-2 was 3.5%, 3.6%, and 6.0 respectively in children, adolescents, and adults. Children had a lower incidence of symptoms than adolescents (p = 0.001) or adults (p = 0.003); the most frequent were fever, ageusia, anosmia, headache, dry cough, sore throat, muscle pain, runny nose, dyspnea, and diarrhea. Conclusions We concluded that the prevalence rate for all groups was 26.7% in serology and 4.04% in RT-PCR. Children had lower rates of IgM and fewer symptoms compared to adolescents and adults. The data suggests the potential for transmissibility in all age groups.

In late 2019, the outbreak of an emerging disease due to a new coronavirus, later called SARS-CoV-2, emerged in Wuhan, China, and spread rapidly J o u r n a l P r e -p r o o f worldwide (Lai et al., 2020) . Coronaviruses are simple positive-sense RNA viruses that have a large characteristic genome . In humans, the coronavirus that causes respiratory infection belongs to the genus Betacoronavirus, originating in bats.

SARS-CoV-2 has approximately 79% sequence similarity to SARS-CoV (Lu et al., 2020) . As the number of cases rapidly increased and the disease reached hundreds of countries, WHO declared the COVID-19 epidemic as a pandemic on March 12, 2020 (WHO, 2021a) .

Until April 20, 2021, SARS-CoV-2 had infected approximately 141,594,845 people, killing more than 3,021,39776 in 223 countries and causing social and economic disruption worldwide. Brazil, has been severely affected with a total of 374,682 deaths (WHO, 2021a) . Of these, 78,118 occurred in the Northeast, with 16,2357 in the state of Ceará (BRASIL, 2021a) . In Ceará, almost half the deaths (6303 deaths) were concentrated in Fortaleza, the state capital (Brasil, 2021b) .

COVID-19 has impacted populations with distinct clinical repercussions correlated with age groups. In comparison with adults, the clinical expression of the largest proportion of the pediatric group presents few symptoms. Oligosymptomatic and asymptomatic patients maintain their transmission capacity and are therefore agents of significant epidemiological impact (Dong et al., 2020; Ludvigsson, 2020; Zou et al., 2020) . The pediatric group represents about 1% of hospitalized cases and deaths (Castagnoli et al., 2020) . The most common symptoms described at the onset of the disease are fever (50%) and mild cough (38%) (Jiehao et al., 2020) . Other clinical features include sore throat, rhinorrhea, sneezing, myalgia, fatigue, diarrhea, and vomiting. Children may experience more upper airway problems than lower respiratory symptoms (Dong et al., 2020) and appear to recover in 1-2 weeks .

For this reason, school closures have been implemented almost everywhere globally to prevent the potential spread of COVID-19 (Cohen et al., 2020) .

Globally, educational institutions had to remain closed due to the pandemic, as part of the effort to ensure social distancing to contain the transmissibility of the disease (Shah et al., 2020) . Children are seen as important transmitters of COVID-19 (Macartney et al., 2020) . In Brazil, a special regime for remote school activities was adopted as of March 19, 2020, under MEC Ordinances nº 345, which authorized teaching activities using digital educational resources, information and communication technologies, or other conventional means in public and private schools (Brasil, 2020) .

Although some teaching and learning activities can be carried out through the remote mode and the closure of schools is a crucial measure of containment, it must be noted that the disruption of regular classroom education has significant social and economic impacts on society, at the regional, national, and global levels (Macartney et al., 2020) . Also, children from disadvantaged backgrounds are more likely to suffer from school closure, not only in terms of academic learning but also due to loss of access to free school meals and social services (Viner et al., 2020) .

During the remote learning period, conflicts between educational institutions, public administrators, educators, and parents were fueled by the lack of certainty about how safe it is for children to attend school and how long would should the remote learning period last, questions that have been dealt with very carefully by other countries (Ismail et al., 2021) . To fill these information gaps, epidemiological studies seek to provide data to support the formulation of care strategies at different levels to mitigate the risk of spreading SARS-CoV-2 and its variants, in addition to helping the government to take informed and safe decisions regarding the ideal time to reopen schools. In this sense, to prevent a further increase in the number of COVID-19 cases, the relaxation J o u r n a l P r e -p r o o f of physical distance, including the reopening of schools, must be accompanied by largescale testing of symptomatic individuals and effective tracking of their contacts, followed by isolation of diagnosed individuals (Panovska-Griffiths et al., 2020) .

Thus, the present study aims to verify the prevalence of COVID-19 in children, adolescents, and adults in the period of remote education, combining serological and molecular diagnosis, correlating with epidemiological and clinical characteristics.

This was a transversal retrospective study guided by the STROBE tool. The study was conducted by the Institute of the Heart of Children and Adolescents (InCor Criança) in partnership with the municipality of Fortaleza, city located in northeastern Brazil.

Incor Criança is a philanthropic health institution the mission of which is to provide comprehensive and equitable care to the pediatric population.

The city of Fortaleza is the capital of the State of Ceará, with a population of 2, 686,612 inhabitants, of which 852,195 are children and adolescents, with 378,175 between the ages of 0 -9 years and 474,020 between 10 to 19 years (IBGE, 2021).

The city is divided into six educational districts geographically distributed to encompass its entire territory. The education network in Fortaleza is made up of municipal and state schools. The study was carried out in municipal schools responsible for early childhood education and elementary education. 

A multistage sampling procedure was used to recruit children, adolescents, and adults. Cluster sampling was used between the schools belonging to each of the city's six educational districts. Children, adolescents, and adults were excluded if they had any medical condition that prevented or hindered their school attendance.

The study subjects were divided into three age groups: children -individuals aged up to 9 years; adolescents -individuals aged 10 to 19 years; and adults -individuals over 19 years old (WHO, 2014), who were school employees.

The sample size for the groups of children and adolescents was defined based on the total number of students in the municipal education network (229,165 students) for a 95% confidence level and an accuracy level of 2.5%, totaling 1,277 students. The sample of the adult group was made up of all the employees (teachers and administrative professionals) who participated in classroom activities in the schools and who had contact with students during the delivery of supplies (food and school supplies), totaling 282 individuals (Table 1) .

Data collection was carried out in February 2021 through a data search on the online RedCap platform to gather sociodemographic, clinical, and laboratory data from the target individuals studied during the COVID-19 screening carried out from November 9 to December 9, 2020.

The tracking period coincided with the beginning of the second wave of the pandemic, with a moving average value equal to 451.9 cases, 53.44% less than the time series' peak, which was 970.6 cases in May 2020 ( Figure 1 ). Initially, the study participants underwent screening, and when signs or symptoms suggestive of COVID-19 were detected, they were directed to a private environment for an interview, clinical evaluation, and collection of tests.

The individuals were considered symptomatic when they presented signs or symptoms such as fever, cough, rhinorrhea, dyspnea, chest pain, sore throat, ageusia and anosmia, adynamia, muscle pain, diarrhea, headache, vomiting, or skin changes Dong et al., 2020; Jiehao et al., 2020) . They were considered asymptomatic when they had no signs or symptoms of the disease.

Those without signs or symptoms went through the same screening process in another environment and all the sanitary measures of hygiene and social distance were taken, appropriate to the pandemic moment.

Individuals who presented positive serology for IgM or IgM and IgG were submitted to nasopharyngeal and oropharyngeal secretion collection for RT-PCR analysis.

J o u r n a l P r e -p r o o f

Peripheral blood samples were collected from participants by finger puncture.

The presence or absence of IgM and IgG antibodies against SARS-CoV-2 was analyzed using the Leccurate SARS-CoV-2 Antibody Test kit (Beijing Lepu Medical Technology

Co., Ltd), which uses a colloidal gold chromatographic immunoassay technique.

According to the manufacturer's specifications, the protein used for diagnosis is N (nucleocapsid), with a sensitivity of 98.9% and a specificity of 97.6%. 

In the analysis of the participants' characteristics between serology groups and age groups, the Student's t-test and the Mann-Whitney U test were used, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, Pearson's chi-square test and Fisher's exact test were used. A significance level of 5% was adopted. Statistical analyses were performed using the statistical program JAMOVI and Microsoft Excel 2016.

The research data were expressed in tables and graphs. The numerical variables were expressed as mean, standard deviation, minimum and maximum. The categorical variables in the data were exposed in frequency and incidence rate.

Of the 1,277 children and adolescents surveyed, 649 (50.8%) were female. Their ages ranged from 3.8 to 18.7 years old, with a mean of 11.3 years (SD ± 2.7). When evaluated by age group, there were 423 students under 9 years old (33.1%) and 854 between 10 and 19 years old (66.9%).

The socio-economic assessment of the families of children and adolescents showed that 33% of the family's providers were unemployed, 26.1% were employed, and 36.4% were self-employed. 20.8% of families lived on less than the US $207 per J o u r n a l P r e -p r o o f month, and the income of 75.6% of families was between US $207 to US $621. 74.1% participated in social programs and 41.2% in exceptional social protection measures to face the pandemic (emergency aid).

Children and adolescents expressed 28% seroprevalence; children with a prevalence of 25.3% distributed in IgM + IgG (4.7%), IgG (18%) and IgM (2.6%) and adolescents with a prevalence of 29.2% distributed in IgM + IgG (9.7%), IgG (15.3%) and IgM (4.2%) ( Table 02 ).

The majority (73.7%) was asymptomatic at the time of the evaluation or in the last 21 days. The remaining (26.3%) had symptoms such as fever (16.2%), ageusia (11.5%), anosmia (10.9%), headache (9.5%), dry cough (8.1%), sore throat (7.8%), muscle pain (5%), runny nose (4.8%), dyspnea (2.8%), diarrhea (2.8%), adynamia (2.2%), vomiting

(1.7%), chest pain (0.6%), hives (0.6%), and pruritus (0.3%).

Children and adolescents with positive serology had comorbidities in 32.2%, with those associated with atopy components being more frequent, such as respiratory in 8.4%, and cutaneous in 17.4%.

When we assessed the contact of children and adolescents for serology for IgM with symptomatic family members in the last 21 days before testing, we demonstrated that 6.5% of IgM positive children and 3.9% of those IgM negative remained in contact, without statistical significance (p = 0.626). In adolescents, 5.9% of positive IgM and 2.3% of negative IgM maintained contact, with no statistical significance p = 0.200.

The seropositive prevalence rate was highest in district III (37.8%), followed by districts I, II, IV, V, and VI at 34.2%, 31.6%, 29.7%, 21.6%, and 18.1%, respectively.

RT-PCR tests were performed on 150 children and adolescents who expressed IgM or IgM + IgG, 52% of whom were female. Their ages ranged from 6.5 to 16 years with a mean of 11.24 years (SD ± 2.41), and in those who tested negative, ages ranged J o u r n a l P r e -p r o o f from 5.3 to 17.5 years, mean 12.35 SD ± 2.44. Of the 31 children tested, SARS-CoV-2 was detected in 48.4%, which represents 3.5% of the total children analyzed. Among adolescents, 26.1% tested positive, 3.6% of the total sample. It was observed that children under 9 years old were 2.6 times more likely (I.C. 95%: 1.17 -6.01) to present positive RT-PCR compared to adolescents, p = 0.018 (Table 03) .

Of those with positive RT-PCR, 76.1% were asymptomatic at the time of the exam or in the past 21 days. The symptomatic children and adolescent (23.9%) presented fever (20%), ageusia (11%), headache (11%), anosmia (9%), sore throat (9%), muscle pain (7%), dry cough (7%), diarrhea (4%), vomiting (2%), adynamia (2%), and hives (2%).

Of the 282 adults evaluated, 207 (73.4%) were female. Their ages ranged from 19 to 72 years, with an average of 45.38 years (SD ± 10.17). Of these, 59 (20.9%) were confirmed with positive serology, distributed between IgM (5%), IgG (7.4%) and IgM + IgG (8.5%), Table 02 .

Of those tested with positive serology (IgG, IgM, or IgM + IgG), 45.8% were asymptomatic at the time of the evaluation or in the last 21 days. They were symptoms in 54.2% such as ageusia (32%), fever (29%), headache (27%), anosmia (24%), muscle pain (20%), dyspnea (19%), adynamia (19%), sore throat (19%), runny nose (17%), dry cough (12%), chest pain (8%), diarrhea (7%), vomiting (7%), hives (7%), and others (2 %).

Of the 37 adults who expressed IgM or IgM + IgG, 17 (45.9%) tested positive for the detection of SARS-CoV-2 by RT-PCR, which represents 6.0% of the sample. Of J o u r n a l P r e -p r o o f these, 9 (52.9%) were female. Age ranged from 28 to 61 years, with a mean of 45.9 (SD ± 9.9 years), as shown in Table 03 .

In adults with positive RT-PCR, 52.9% were asymptomatic at the time of assessment or in the past 21 days. They were symptoms in 47.1% such as ageusia (35.3%), headache (35.3%), anosmia (29.4%), adynamia (29.4%), sore throat (23.5%), fever (23.5%), muscle pain (17.6 %), runny nose (17.6%), and chest pain (11.8%), and dyspnea, vomiting, dry cough, and allergy with (5.9%) each.

When comorbidities were evaluated for the group of adults with positive RT PCR, the most frequent were hypertension (HTN) (23.5%), allergy (11.8%), diabetes mellitus -DM (5.9%), hypercholesterolemia (5.9%), and asthma (5.9%).

In analyzing the prevalence of positive serology for COVID-19 among the age groups, a significant association was detected between these variables, p = 0.017, with adults showing the lowest prevalence (20.9%) when compared to adolescents (29.3%), p = 0.018. There was no difference in the prevalence of positive serology for COVID-19 between children and adolescents and between children and adults.

In the analysis of IgM's prevalence in the age groups, there was a significant difference in the prevalence rate between children and adolescents, p = 0.003, where children under 9 years old presented 7.3% of IgM positivity against 13.9% of adolescents. Children also had a lower prevalence rate than adults, 13.5% and p = 0.021. In comparing adolescents and adults, there was no difference between the prevalence rates of IgM positivity, p = 0.846.

In the analysis of the prevalence of IgG in the age groups, making the Bonferroni As for the presence of symptoms of COVID-19 on the day or up to 21 days before the exam, there was a significant association of this variable as the age group, p = 0.001, where those younger than or equal to 9 years old had the lowest incidence of symptoms compared to adolescents, p <0.001, or adults, p = 0.003.

Children and adolescents had lower comorbidities than adults. The most frequent in this last group were HTN, DM, hypercholesterolemia, and cancer.

In the analysis of the symptoms of the three groups, both serology and positive RT-PCR, there was a significant association with ages group: chest pain and fatigue, both with p <0.001; sore throat, p = 0.009, and diarrhea, 0.039; with a higher incidence in adults and with no difference between children and adolescents. Muscle pain and J o u r n a l P r e -p r o o f dyspnea with p <0.001, with a difference in incidence between the three age groups, in which children under 9 years old had the lowest incidence of these symptoms and adults the highest incidence. Anosmia and ageusia (p <0.001) had a lower incidence among children under 9 years old and no difference between adolescents and adults.

It was observed that 7.3% of the population of children and 13.9% of adolescents (Table 04) .

This study evaluated the results of RT-PCR for SARS-CoV-2 and serology for 

In our study, we identified a significant difference in the prevalence of IgM in children and adolescents, where children presented 7.3% positivity of IgM against 13.9% of adolescents. Children also had a lower prevalence rate than adults (13.5%).

Comparing adolescents and adults, there was no difference between the prevalence We did not observe a significant difference between children and adults and between adolescents and adults regarding the prevalence of positive RT-PCR.

However, there was a significant difference in the prevalence rate between children and adolescents, where children under 9 years old had a higher positivity rate, with 2.6 times greater positivity RT-PCR.

Of the total number of individuals assessed in the study, 1,227 (children and adolescents) and 282 (adults), the estimated rate for positive RT-PCR was 3.5% in children, 3.6% in adolescents, and 6% in adults.

In a study carried out with 605 children, Cohen et al. (2020) demonstrated that the RT-PCR test and serology were positive for 1.8% and 10.7% of all children, respectively. The frequency of positivity in the RT-PCR for SARS-CoV-2 was significantly higher in children with positive serology than those with negative serology.

In a preliminary investigation with adults and symptomatic school students in France, Fontanet et al. (2020) showed that 16.7% of adults and 8.3% of students had an acute infection, as determined by a positive RT-PCR test.

Since antibodies (IgM/IgG) against SARSCov-2 are detectable only around day 7, from the onset of symptoms (in approximately 50% of cases), a negative serological J o u r n a l P r e -p r o o f result during the first 7 days of the disease cannot be used as criteria to rule out a case (Sethuraman et al., 2020) . Sensitivity in the detection of total antibodies increases from the second week after the onset of symptoms and, on the 14th, more than 90% Some researchers show that this occurs from 1-2 days before the onset of symptoms in samples of the upper respiratory tract, which can persist for 7-12 days in moderate cases and up to 2 weeks in severe cases ( WHO, 2021b) , and others point to around 20 days (Chen, 2020; Lippi et al., 2020; Xiao et al., 2020) . However, this period cannot be taken as a rule, as another screening study that compared RT-PCR and serology showed that whoever presented positive serology may or may not have circulating viral RNA (Cassaniti et al., 2020) .

We demonstrated that in children and adolescents, 73.7% of those seropositive and 76.1% of those virologically confirmed by RT-PCR were asymptomatic at the time of the evaluation or in the last 21 days. The most frequent symptoms in children and adolescents were fever, ageusia, anosmia, headache, dry cough, and sore throat.

The literature is unclear regarding the percentage and type of symptoms that are more prevalent in this group. Cohen et al. (2020) showed that in 605 children tested, 53.2% were asymptomatic. In a review of 2,143 pediatric cases, Dong et al. (2020) demonstrated that in virologically confirmed children, 13% were asymptomatic. Jiehao et al. (2020) described the most common symptoms such as fever (50%) and mild cough (38%). Other clinical features included sore throat, runny nose, sneezing, myalgia, fatigue, diarrhea, and vomiting. Dong et al. (2020) highlighted that children might have more problems in the upper airways than lower respiratory symptoms.

Thus, epidemiological inferences may not represent the reality, as asymptomatic children are less likely to be tested and still contribute to transmission (Dong et al., 2020) . Corroborating this statement, Zou et al. (2020) analyzed the relationship between viral load and symptoms in infection in 18 patients with COVID-19 and found that the pattern of viral nucleic acid excretion in those with SARS-CoV-2 infection was similar to influenza and that the viral load determined in asymptomatic patients was similar to patients with symptoms, which indirectly suggested the potential for transmission in asymptomatic or mild cases with COVID-19. Maltezou et al. (2021) suggest that the transmission direction is from adult to child. However, since the study was based on the dates of the PCR test and because adults have symptoms in greater proportions than children, more adults may be identified first, and positive children may be assessed as secondary cases.

When comparing the groups regarding the presence of symptoms, children had fewer symptoms than adolescents and both less than adults. Among the symptoms reported by participants in the three groups, chest pain, sore throat, muscle pain, dyspnea, fatigue, and diarrhea were more prevalent in the adult group.

Several reports have shown that children and young adults experience a milder form of the disease than adults. Asymptomatic, mild, and moderate infections are present in more than 90% of all children who have tested positive for COVID-19. Critical cases represent 5.9% in children, different from adults who express rates of 18.5% (Dong et al., 2020) .

Possible reasons for the lower number and lower degree of infections in children and young adults include less exposure to the virus due to home isolation and less exposure to pollution and cigarette smoke, contributing to healthier airways. The distribution, maturation, and functioning of viral receptors such as ACE2 (Angiotensin Converting Enzyme) may be important in susceptibility to severe, age-dependent COVID-19 (Dong et al., 2020; Lee et al., 2020) . Another reason for infections with less impact in the pediatric group is the lower abundance of anti-N-specific antibodies since the release of N proteins requires the lysis of cells infected by the virus (Weisberg et al., 2021) .

Publications highlight the increase in the home infection rate by the proportion of family groups with at least one member presenting COVID-19 infection (Hubiche et al., 2021) or refer that the majority of infected children are likely to be secondary to exposure to a confirmed adult COVID-19 case (Jiehao et al., 2020) . Our study found no association between children and adolescents seropositive for IgM and contact with a family member with COVID-19. Hubiche et al. (2021) and Jiehao et al. (2020) agree that intra-family transmission is not yet fully understood, requiring longitudinal data to confirm these inferences. A French study evaluating the spread of COVID-19 concluded that in the context of increased viral transmission in the population, the spread among children and adolescents remained lower than that observed among adults, despite keeping J o u r n a l P r e -p r o o f schools open. However, the impact was age-dependent, with data from high schools close to that of adults (Guen et al., 2021) .

A study of infection and transmission in England showed a significant correlation between outbreaks in educational settings and the incidence of COVID-19 in the community, even during a period of low incidence in the community (Ismail et al., 2021) .

Another characteristic of children and adolescents was a low frequency of associated diseases. Adults had more comorbidities represented by hypertension, diabetes mellitus, hypercholesterolemia, and cancer.

It is worth mentioning that the comorbidities preceding COVID-19, such as cardiovascular disease, chronic kidney disease, chronic lung diseases, diabetes mellitus, hypertension, immunosuppression, obesity, and sickle cell anemia, predispose

to an unfavorable clinical course, with increased risk of intubation and death (Cecconi et al., 2020; Huang et al., 2020; Zhou et al., 2020) . Almost 90% of fatal cases have occurred in patients aged 65 and over (Tehrani et al., 2021) . On average, it is observed that it is rare for infected children to be hospitalized, and less than 1% of pediatric cases can be fatal (Pierce et al., 2020) .

Finally, for the population of children and adolescents in the period studied in The study has several limitations: no data were collected in students' homes;

instead, children and adolescents were invited to attend school institutions, and sick individuals may not have attended. Further, all participants were not submitted to SARS-

CoV-2 verification by RT-PCR, failing to surprise genetic material of the virus in moments before IgM positivity, which may have underestimated the prevalence rates.

Based on the above, we hope that this study will support the planning of public policies that recognize the potential for transmissibility of COVID-19 by children and adolescents, even those who are asymptomatic; that this group may maintain contact with vulnerable adults in home environments; that effective sanitary measures should be implemented when returning to presential activities; and that investments in research in the field of diagnosis, treatment, and prevention are needed.

In summary, after the peak of the first epidemic wave and during the distance education period, our data identified a prevalence rate, for all groups, of 26.7% in serology (IgM and IgG) and 4.04% in RT -PCR. Children have lower rates of positivity for IgM and fewer symptoms compared to adolescents and adults. The data suggest the potential for transmissibility in all age groups. The return to classroom activities in schools should be considered with continuous monitoring and health strategies to mitigate transmission. This study should be continued after returning to classroom activities to understand the disease's behavior better.

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