SARS-CoV-2 infection characteristics among students and staff in a large high school COVID-19 outbreak and secondary transmission in households

Abstract

Background

SARS-CoV-2 clinical presentation is associated with the patients’ age group. Overall, young individuals present higher proportions of asymptomatic or mild COVID-19 infection, compared to adults. Data on secondary COVID-19 transmission in households, according to the cases’ age group, are accumulating.

Methods

We performed a follow-up cohort study including all COVID-19 real-time polymerase chain reaction (RT-PCR)-confirmed cases (adolescent students and school staff) diagnosed in an epidemiological investigation of a large high school outbreak. We compared the adolescent and adult groups regarding clinical symptoms, time to negative COVID-19 RT-PCR tests, and infection transmission in households.

Results

The study population included 817 persons. The confirmed COVID-19 RT-PCR outbreak cases (n = 178) were followed (students aged 12–19 years, median age 14 years, n = 153, school staff aged 24–67 years, median age 39 years, n = 25) and the cases’ household close contacts (n = 639) were tested. The adolescents had lower symptomatic infection rates, shorter time to negative COVID-19 RT-PCR tests, and lower transmission rates to household members, compared to the adults. The general transmission rate among household contacts was 13.5%, (86/639) ranging from 8.6% in asymptomatic students’ contacts to 27.3% in symptomatic staff contacts. COVID-19 transmission rates were significantly higher in contacts of symptomatic cases compared to asymptomatic cases (odds ratio: 2.06, 95% CI 1.26–3.4) and higher in adults compared to adolescents (odds ratio: 2.69, 95% CI 1.43–4.89).

Conclusions

Adolescents and adults diagnosed in an outbreak investigation differ as to COVID-19 clinical presentation and transmission. As adolescents may show mild or no symptoms, COVID-19 prevention in school settings is challenging. Implementing nonpharmaceutical measures and promoting vaccination programs in eligible staff and students should be considered.

Graphical abstract

1. Introduction

World-wide, the number of SARS-CoV-2 coronavirus disease (COVID-19) cases has exceeded 630 million with over 6 million fatalities [1]. The SARS-CoV-2 clinical presentation may range from asymptomatic or mild to severe disease, complications, and mortality; severity is associated with increasing patients’ age [2,3]. A systematic review on COVID-19 clinical presentation among children and adolescents showed that 14.6%–42% were asymptomatic. Fever (46.0%–64.2%) and cough (32.0%–55.9%) were the most frequent symptoms; rhinorrhea, sore throat, headache, fatigue/myalgia, diarrhea and vomiting, loss of smell, (anosmia), and taste (ageusia) were less common [4]. Overall, young children often present with asymptomatic or mild COVID-19 infection was linked with less transmission [5]. COVID-19 clinical presentation and disease course tend to be milder, with a fair prognosis and fewer hospitalizations, complications, and mortality, in children and adolescents than in adults [3,[6], [7], [8]]. The role of children in SARS-CoV-2 transmission has been reported as less dominant than in adults; also, seroprevalence rates were lower in children compared to adults, while rates in adolescents were comparable to adults [9]. Nevertheless, strategies targeted to reduce COVID-19 transmission—lockdowns, prolonged closure of educational settings, and social distancing measures have profoundly affected the well-being of the young population in many countries [10].

Assessing the COVID-19 presentation and transmission in schoolchildren is hence necessary. At the end of May 2020, a COVID-19 outbreak emerged in a Jerusalem high school, 10 days after schools’ reopening, affecting some 180 students and staff members [11]. The outbreak was the largest single COVID-19 event in a school setting. The epidemiological investigation included testing the school community by COVID-19 real-time polymerase chain reaction (RT-PCR). Subsequent to the outbreak investigation, we aimed to perform a follow-up study of all the school's COVID-19 RT-PCR-confirmed cases. The characteristics studied included the clinical symptoms, the time to negative RT-PCR tests, and the COVID-19 infection transmission patterns in households.

2. Materials and methods

The COVID-19 school outbreak necessitated prompt epidemiological investigation and containment [11]. The school community includes students (adolescents aged 12–19 years) and staff (adults aged 24–67 years). The Jerusalem district health teams performed the investigation in June-September 2020. The school attendees complied with COVID-19 RT-PCR tests (151/152 of staff and 1161/1164 of students). The Jerusalem health funds laboratories performed the standardized COVID-19 RT-PCR tests. COVID-19 was confirmed in 178 persons, 153 students (attack rate 13.2%), and 25 staff members (attack rate 16.4%).

This follow-up study assembled the epidemiological investigation data. The school community was defined as a cohort group. The study variables included the cases’ demographics, self-reported clinical symptoms, COVID-19 RT-PCR tests results—until the date of negative RT-PCR tests, and the contact tracing among household members.

The study population included 817 persons. All the school's confirmed cases (n = 178) were followed. The household members (n = 639) were defined as close contacts and underwent COVID-19 RT-PCR tests. The district health teams performed telephone interviews with the school staff, parents, and students and offered counseling to the school community, on isolation requirements and various queries. The epidemiological interview included self-reporting of clinical symptoms. Cases were defined as symptomatic when the laboratory confirmed and reported on at least 1 clinical symptom and as asymptomatic when the laboratory confirmed and not reporting clinical symptoms.

The follow-up included COVID-19 RT-PCR tests, consistent with the Ministry of Health (MoH) guidelines of a test-based approach (later switched to a time-based approach). The test-based approach defined “recovery” in symptomatic confirmed cases as symptom-free for at least 48 hours and having 2 consecutive, 72-hours-apart, negative COVID-19 RT-PCR results, the first taken at least 7 days after symptoms onset. Asymptomatic confirmed cases required 2 consecutive negative COVID-19 RT-PCR results, 72-hours-apart, the first taken at least 5 days after the first positive test. For the study, we used the MoH definition (days between the first positive and the second consecutive negative COVID-19 RT-PCR tests).

In May 2020, in Israel, the virus type was the SARS-CoV-2 wild type (Wuhan). The data regarding the COVID-19 RT-PCR tests’ results were retrieved from the national database. The threshold cycle (Ct) values for the study participants were unavailable in the database. The MoH guidelines (May 2020) defined a positive test result when the viral genome was detected at Ct values ≤35, indeterminate between >35 and ≤38, and negative with Ct >38.

The study variables included age, gender, reported clinical symptoms, COVID-19 PCR test results, the follow-up to 2 negative results, COVID-19 PCR test results in the household members, and characteristics of COVID-19 confirmed household contacts. The distribution of clinical symptoms was assessed in students and school staff. The association between time to second negative result (in days) and symptoms were evaluated. The infection transmission rates were assessed according to the tests' results in the household members. The rates of infection transmission were compared between symptomatic and asymptomatic cases.

The data analysis was performed with IBM SPSS Statistics (Version 28.0.: IBM Corp.). The comparisons of proportions between the study groups were performed by calculating odds ratio (OR) and Rate Ratio (RR) with the 95% confidence intervals (95% CI). Pearson χ² test was used for comparing categorical variables and T test was used for comparing continuous variables. OR and RR was calculated for the comparisons of proportions between the study groups with 95% CI. We calculated the p-values using Fisher Exact test. The medians of the time to the second negative COVID-19 PCR result (in days) were compared by the independent sample median test between groups. A logistic regression analysis model was applied to evaluate the possible variables associated with COVID-19 infection transmission to household members. The variables entered into the logistic regression model were assessed for correlation (all under 0.3). A p-value <0.05 was considered significant for all comparisons.

This study was approved by the MoH, Israel, and was performed according to the MoH national guidelines and ethical instructions established for COVID-19 epidemiological studies (https://data.gov.il/dataset/covid-19).

3. Results

COVID-19 infection was confirmed by COVID-19 RT-PCR tests in 178 persons, 153 students, and 25 staff members. The COVID-19 cases’ characteristics are presented in Table 1. Of the 153 students, 97 (63.4%) were aged 12–14 years and 56 (36.6%) were aged 15–19 years. The rate of reported COVID-19 clinical symptoms was significantly lower in the adolescent students, 43.1% (66/153) compared to 76% (19/25) among the adult staff. Notably, all the school staff members who were over 50 years of age (n = 8) reported on clinical symptoms.

Table 1.

Characteristics of the COVID-19 cases (n = 178, school students and staff) and comparison of main outcomes.

Characteristic	School students n = 153 (%)	School staff n = 25 (%)	RR (95% CI)	OR (95% CI)	p
Age (mean ± SD) years	14.1 ± 1.3	43.4 ± 13.8
Age (median) years	14	39
Age (range) years	12–19	24–67
Gender
Female	70 (45.8%)	16 (64%)	1.5 (0.9–2.6)	2.1 (0.8–5.7)	0.07
Males	83 (54.2%)	9 (36%)
Clinical symptoms
No symptoms	87 (56.9%)	6 (24%)	2.4 (1.2–4.8)	4.2 (1.5–13.4)	0.002
Any symptoms	66 (43.1%)	19 (76%)
1 clinical symptom	30/66 (45.5%)	4/19 (21.1%)	2.2 (0.9–5.4)	3.1 (0.9–14.1)	0.047
>1 clinical symptom	36/66 (54.5%)	15/19 (78.9%)
Muscle aches	6/66 (9.1%)	8/19 (42.1%)	4.6 (1.8–11.7)	7.3 (1.8–30.2)	0.002
Negative PCR test on follow-up day 21	52/153 (34%)	2/25 (8%)	4.2 (1.1–16.4)	5.9 (1.4–53.4)	0.005
Secondary COVID-19 transmission to household contacts (n = 639)	66/563 (11.7%)	20/76 (26.3%)	2.2 (1.5–3.5)	2.7 (1.4–4.9)	0.001

The clinical symptoms were assembled into 3 groups, general symptoms (fever>38°C, headaches, fatigue, dizziness, chills, muscle aches, and loss of smell or taste), respiratory (cough, sore throat, rhinorrhea, and shortness of breath) and gastrointestinal (diarrhea, vomiting, and abdominal pain). General symptoms were more common in the staff while gastrointestinal symptoms were more common in students (Fig. 1). The most common symptoms reported were cough, headache, and fever. The rates of reported symptoms differed significantly between students and staff (Table 1), regarding more than 1 clinical symptom (78.9% in staff, 54.5% in students) and muscle aches (42.1% in staff, 9.1% in students). No difference in rates of reported symptoms was observed between males and females.

Fig. 1.

Rates of clinical symptoms in COVID-19 confirmed cases (students and school staff). Rates of clinical symptoms (percentage) reported by the COVID-19 confirmed cases (n = 178) - students aged 12–19 years, n = 153 and school staff aged 24–67 years, n = 25. Rates of symptoms showing significant difference between students and school staff are marked with * or **.

Overall, 852 COVID-19 RT-PCR tests were performed in the 178 school cases' follow-up. The mean number of COVID-19 RT-PCR tests per case was 4.8 ± 1.5 (median 5), and 101 of the cases (56.7%) received 5 consecutive COVID-19 RT-PCR tests and above. These repeated COVID-19 RT-PCR tests enabled assessment of the time period (days) to reach the definition of “recovery” according to the applicable MoH guidelines test-based approach. Cases were retested until having a second consecutive negative COVID-19 RT-PCR result. The median time to second negative result in all cases was 26 days, 96.6% (172/178) were negative by day 32. The period was shorter in students (mean 24.4 ± 6.7, median 25 days) than in staff (mean 27 ± 4.4, median 27 days). Figure 2 shows the proportion of cases with a second negative COVID-19 RT-PCR result, by days, according to reporting on symptoms. Until follow-up day 22, 44.1% of asymptomatic vs. 25.9% of symptomatic cases were negative (OR: 2.26, 95% CI 1.14–4.5, p = 0.008); until day 25, the proportions were 59.1% vs 38.8%, respectively (OR: 2.28, 95% CI 1.2–4.35, p = 0.005). Asymptomatic cases (mean 23.9 ± 6.2, median 24 days) showed shorter (p = 0.04) periods than symptomatic cases (mean 25.8 ± 6.6, median 27 days). No difference was observed between males and females.

Fig. 2.

RT-PCR tests follow-up, in symptomatic and asymptomatic COVID-19 confirmed cases. COVID-19 RT-PCR tests follow-up by time (in days), in the COVID-19 confirmed cases (n = 178) according to having clinical symptoms. Rates of negative tests showing significant difference between symptomatic and asymptomatic cases are marked with * or **. RT-PCR, real-time polymerase chain reaction.

The household members of the school cases were defined as close contacts and eligible for COVID-19 RT-PCR tests regardless of having clinical symptoms. Household members of students and staff (n = 563 and n = 76 persons, respectively) were tested. Of the 639 household members tested, 86 persons (13.5%) were confirmed with COVID-19 infection. Among these 86 persons, in 26 (30.2%) there was 1 COVID-19 confirmed household member, in 28 (32.6%) 2 members, and in the remainder—3 and above (n = 32, 37.2%). Of the 639 household members, the transmission rates were higher in adults (71/279, 25.5%) compared to children under 19 years (15/360, 4.17%), (RR: 2.2, 95% CI 1.5–3.5, OR: 7.85, 95% CI 4.3–15.1, p = 0.001). Figure 3 displays transmission rates according to the cases’ groups. The COVID-19 infection transmission rates differed with 11.7% (66/563) in the students’ household members and 26.3% (20/76) in the staff household members (OR: 2.7, 95% CI 1.43–4.9, p = 0.001). Overall, the rates of COVID-19 infection transmission to household members were higher in symptomatic cases (17.8%, 54/303) compared to asymptomatic cases (9.5%, 32/336) (RR: 1.87, 95% CI 1.24–2.8, OR: 2.06, 95% CI 1.26–3.4, p = 0.002). The Crude OR comparisons of infection transmission between the groups, regarding age group and having COVID-19 symptoms are presented in Figure 4. Notably, the highest odds for transmission, related to symptoms, were observed among students aged 15-19 years (OR: 6.37, 95% CI 2.39–18.69, p = 0.001).

Fig. 3.

Secondary transmission rates among household contacts of COVID-19 confirmed cases. Secondary transmission rates, among household contacts (n = 639) of COVID-19 confirmed cases (n = 178), according to age group (adolescent students or school staff) and clinical symptoms (symptomatic and asymptomatic cases). Significant differences are marked with * or **.

Fig. 4.

Odds ratio (95%CI) of infection transmission rates between the study groups. The comparisons of Crude odds ratio (95% CI) of infection transmission rates between the groups, with regard to the age group and having COVID-19 symptoms, including the study population: cases (178 confirmed cases: 25 adults, 97 adolescents aged 12–14 years, 56 adolescents aged 15–19 years) and household contacts (n = 639). CI, confidence interval.

A multivariate regression analysis model evaluating the dependent variable ‘COVID-19 infection transmission in the household’ included the variables: age group (students vs school staff), gender, and being a symptomatic COVID-19 case vs asymptomatic. In the final model, being symptomatic was significantly associated with transmission. (Adjusted OR: 2.04, 95% CI 1.02–4.09, p = 0.04).

4. Discussion

This study describes a school-based follow-up of COVID-19 confirmed cases, among adolescent students and adult staff. As nearly all school attendees were tested, the group comprised both symptomatic and asymptomatic cases. The adolescents (median age 14 years) had lower symptomatic infection rates, shorter time to negative COVID-19 RT-PCR tests, and lower transmission rates in households, compared to the adults. Notably, during 2020, the first year of the pandemic, the operational classifications (issued by the MoH) of case definition (based on positive PCR laboratory results with or without clinical symptoms) and the “case recovery” definition evolved considerably. The follow-up in our study included repeated COVID-19 RT-PCR tests, consistent with the MoH guidelines in 2020 of a test-based approach (later switched to a time-based approach). The study definitions were all according to the MoH clinical guidelines at the time of the outbreak investigation and follow-up., the cases underwent repeated COVID-19 RT-PCR tests (with a median of 5 PCR tests) and were followed for 25 days and above.

The general transmission rate in households was 13.5% ranging from 8.6% in asymptomatic students’ contacts to 27.3% in symptomatic staff contacts. The odds for transmission were highest among the adolescent students aged 15–19 years. In a multivariate analysis, the COVID-19 transmission rates were higher among the household contacts of symptomatic cases compared to asymptomatic cases.

Children younger than 19 years comprise 36.1% of Israel's population [12]. During February 1, 2020-August 1, 2021, 37.8% of 855,000 confirmed COVID-19 cases nationally were aged 0–19 years. Young children (0–9 years) and adolescents (10–19 years) were 15.7% and 22.1% of COVID-19 cases and 19.7% and 16.4%, of the national population, respectively [12,13]. In the Jerusalem District, 44.7% of the population is under 19 years [12]. During the above period, 187400 confirmed COVID-19 cases were notified in the Jerusalem District. Young children and adolescents were 16.3% and 24.7% of cases and 24.3% and 20.4% of the district's population, respectively [12,13]. Related to their population fraction, young children were under-represented and adolescents were overrepresented among COVID-19 cases.

A systematic review and meta-analysis [9] assessed the susceptibility to SARS-CoV-2 infection in children, adolescents, and adults, concluding that children (aged under 10–14 years) probably have lower susceptibility while rates in adolescents are similar to adults. Another meta-analysis [14] evaluated susceptibility and SARS-CoV-2 transmission in children (age 0–19 years) and adults, in community, and educational-settings. Compared to adults, adolescents (10–19 years) had similar rates and children aged under 10 years had lower rates.

Similar to our data, SARS-CoV-2 manifestations have been associated with cases’ age groups in reports from many countries including Israel [[6], [7], [8],15]. These age-based differences probably reflect pathophysiological and immune pathways [16]. For example, in younger individuals’ airways, lower activity of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Differences regarding younger individuals’ immune systems include CD4⁺ T cells abundance, reduced neutrophil infiltration, declined proinflammatory cytokines, and increased immunomodulatory cytokines [16]. A study evaluating antibody response in adult and pediatric patients (New York, March-June, 2020) also showed considerable differences [17]. Adults had anti-spike (S) IgG, IgM, and IgA and anti-nucleocapsid (N) IgG antibodies. Children showed mainly anti-S IgG antibodies (but not anti-N) and reduced neutralizing activity, compared to adults [17].

During the SARS-CoV-2 pandemic, households have been repeatedly reported to be a central location for infection transmission. The household transmission in this study was 13.5%, varying between the households of students, staff, and symptomatic vs asymptomatic cases. The SARS-CoV-2 transmission rates in households vary between settings and populations. A systematic review assessing secondary attack rates of SARS-CoV-2 in household contacts, found wide variation across countries, with a lowest reported rate of 4.6% and highest reported rate of 49.6% [18]. A study on household transmission in an ultraorthodox city in Israel showed that children aged 5–17 years and aged 0–4 years were less likely (61% and 47%, respectively) to have positive PCR results compared to adults in the same household [19]. Another systematic review and meta-analysis, on the intrahousehold and close-contact transmission of SARS-CoV-2 [20], showed similar estimates in households of children and adults (a pooled secondary attack rate for a child index case of 13.4% and 12.3% in adults). An updated systematic review and meta-analysis on the household transmission of SARS-CoV-2 [21] showed an estimated secondary attack rate in households of 18.9%. The estimated rate increased from 13.4% (January-February 2020) to 31.1% (July 2020-March 2021).

The role of schools and educational facilities in COVID-19 transmission posed a challenge during the pandemic [11]. A study from England [22], during the months of schools re-opening and national lockdowns, showed that SARS-CoV-2 trends in school-aged children were similar to the trends in adults and reflected the community infection rates. A study in primary schools (ages 5–13 years) in Norway [23] reported very low rates of child-to-child (0.9%) and child-to-adult (1.7%) transmission. A study from a large health maintenance organization in Israel [24], including 1032 cases under 18 years (median age 12 years) indicated that the fraction of primary cases in children did not change after the reopening of educational facilities. A study on COVID-19 incidence rates before and after school reopening in Israel [25], showed that children (aged 0–9 years) did not show increased rates during school attendance periods, while adolescents (aged 10–19 years) showed an increase similar to young adults. A study evaluating COVID-19 transmission in school bubble groups in Catalonia, Spain [26], showed that transmission was limited, with higher rates in older (high school and the last years of middle school) compared to younger children (preschool).

The European Centre for Disease Prevention and Control assessed COVID-19 in children and the role of school settings in transmission [27]. The emergence of variants of concern triggered transmissibility in all age groups. With the increasing COVID-19 vaccines coverage in adults, the fraction of children in all cases may surge [27]. Respectively, in the United States, COVID-19 cases, emergency department visits, and hospital admissions in children (aged 0–17 years) increased in 2021. The rise in child emergency department visits and hospitalizations was inversely linked to the states’ population vaccination coverage [28].

The COVID-19 pandemic's effect on children and adolescents has been extensive, due to changes in daily life routines and frequent alterations in learning activities and school attendance [10]. A review of the COVID-19 pandemic's social and environmental effects on children reported numerous consequences. These include depressive mood symptoms, anxiety symptoms, suicidal ideation, changes in sleep quality, and potential developmental delays [29]. The overall and long-term effects of the global COVID-19 pandemic on child and adolescent health require surveillance and increased awareness of physicians [30].

The findings of our report are subject to several limitations. It is an observational description, including all the COVID-19 cases revealed in an outbreak event investigation and follow-up. Hence, it might be challenging to generalize the findings. The educational facilities conditions and the households’ size and crowding may differ considerably between settings and populations. This outbreak occurred prior to the emergence of COVID-19 variants of concern, some of which may show different presentations or higher transmissibility patterns. The outbreak occurred prior to the availability of commercial vaccines against COVID-19.

In late December 2020, vaccination of persons aged 16 years and above against COVID-19 (BNT162b2 vaccine) started in Israel. In June 2021, subsequent to a rise in COVID-19 in children and schools outbreaks, vaccinations were extended to adolescents aged 12–15 years. In November 2021, the MoH endorsed vaccinating children 5–11 years' old [15,31].

5. Conclusions

We found that adolescents and adults show different COVID-19 clinical presentations and transmission in households. Transmission rates are significantly higher in household contacts of symptomatic COVID-19 cases. As many adolescents may show mild or no symptoms, prevention of COVID-19 spread in schools is challenging. Implementing of various nonpharmaceutical measures [32] and promoting vaccination programs in eligible staff and students in schools should be considered.