Since the start of the COVID-19 Pandemic in Wuhan, China,1,2 multiple clinical manifestations of systemic and neurologic origin, related to infection by this virus have been published, including: vertigo, headache, hypogeusia and hyposmia/anosmia.
Based on data collected from COVID-19 cases in China, at-risk populations such as those over 60 and patients with comorbidities have been described, suggesting that children are at lower risk, with mild symptoms and fewer complications.3–6
The clinical behavior and epidemiologic characteristics, despite being a widely studied disease, is not entirely known, particularly in Latin America and specifically in Colombia. Since the detection of the first case in Colombia on March 6, 2020, the implementation of a national registry began, but there are no publications that reveal the clinical features of severity, as well as the requirement for care in children.
Objectives
- To describe the epidemiologic data of children between 0 to 17 years of age, with a positive COVID-19 finding in our country.
- Analyze the biostatistical data of this cohort of children with COVID-19 in Colombia.
- To evaluate possible risk factors or association for severity in patients with COVID-19.
METHODS AND MATERIALS
A retrospective analysis was made of the characteristics of a cohort of 5062 patients <18 years of age, until June 16, 2020, reported at the National Institute of Health—INS (https://www.ins.gov.co/News./Pages/Coronavirus.aspx), through the national public access database, with all subjects confirmed with COVID-19.
The confirmation of COVID-19 infection currently depends exclusively on the positivity of molecular tests that are available in our country and are valid in both symptomatic and asymptomatic patients.7 Cases were recorded according to clinical severity described in the Table 1. This information can be viewed at https://www.ins.gov.co/Noticias/Coronavirus/Estrategia%20VSP%20COVID-19%2023072020.pdf. The cases with comorbidity (cancer, autoimmune disease, malnutrition, primary lung disease, diabetes, cardiovascular disease (includes hypertension and stroke), HIV or another immunodeficiency, cancer, kidney disease, hypothyroidism, COPD and asthma, use of corticosteroids or immunosuppressants, malnutrition (obesity and malnutrition) and passive smokers are considered, as severe cases for been in the high-risk group, but age was not considered as a risk factor in the INS database.8
Table 1. -
Definitions of Clinical Severity
| Symptomatic case |
Person with acute respiratory symptoms (2 or more of the following: fever, cough, respiratory distress, odynophagia, fatigue, adynamia), or gastrointestinal symptoms (diarrhea, emesis, abdominal pain), which may or may not be associated with Worsening of respiratory symptoms or their persistence on day 8 from their appearance or Lung images with peripheral ground glass or bilateral consolidations With positive PCR test for COVID-19 |
| Asymptomatic case |
Case of close contact, which meets the following criteria: RT-PCR for SARS-CoV-2 in patients with less than 14 d from the date of the last unprotected exposure with confirmed case for COVID-19 |
| Mild case |
Symptomatic case, with upper respiratory symptoms, without requiring hospitalization, Without respiratory distress (dyspnea or tachypnea), without oxygen therapy, associated which meets any of the following criteria: |
| A • SARS-CoV-2 positive RT-PCR in patients with less than 14 days from the date of onset of symptoms |
| In cases where RT-PCR is negative, confirmation of a case that manifested symptoms 11 days before can be evaluated, in addition to: |
| B • Positive serologic test of IgM/IgG antibodies with 11 d or more from the date of the onset of symptoms) |
| The serologic tests used must meet the characteristics of sensitivity and specificity, concordance with PCR and sample size required by the Guidelines for the use of diagnostic tests for SARS-CoV-2 (COVID-19) in Colombia from the Ministry of Health and Protection. Social. |
| Moderate case |
Symptomatic case, with lower respiratory tract compromise, with or without hospitalization, With respiratory distress (dyspnea and tachypnea), without oxygen therapy associated. That meets any of the criteria A or B above |
| Severe case |
Symptomatic case, requiring in-hospital management in emergency services, observation, hospitalization or ICU, which meets any of the criteria A or B above and: |
| • Clinical criteria such as pulmonary radiologic findings (ground glass parenchymal opacities or peripheral consolidation and predominantly basal), increased D-dimer, PCR, ferritin or LDH, as well as lymphopenia and thrombocytopenia. |
| • Characterized as an in risk or vulnerable population. |
| Deceased case |
it is a symptomatic case, which meets one of the following criteria: |
| • Positive RT-PCR for SARS-CoV-2 in patients with less than 14 d from the date of onset of symptoms, in premortem or postmortem test (up to 6 h) in respiratory sample or tissue. |
| • Positive serologic test of IgM/IgG antibodies 10 d or more from the date of the onset of symptoms, in a premortem test. |
| In cases where RT-PCR is negative, the case can be evaluated with the following elements: |
| • Positive serologic test of IgM/IgG antibodies 11 d or more from the date of the onset of symptoms. |
| • Clinical criteria such as pulmonary radiologic findings (ground glass parenchymal opacities or peripheral consolidation and predominantly basal), increased D-dimer, PCR, ferritin or LDH, as well as lymphopenia and thrombocytopenia. |
| • Characterized as an in risk or vulnerable population. |
LDH indicates lactic dehydrogenase; RT-PCR, real time polymerase chain reaction.
Demographic and location characteristics of the case were defined. Statistical tests with measures of central tendency (means) and dispersion (standard error) were applied. A one-way ANOVA test was applied to determine if the age means were different between the groups; In addition, a post hoc analysis was performed with the Tukey’s test to determine possible statistical differences between the analyzed groups. All analyses were conducted using STATA 16 software (StataCorp LLC).
RESULTS
Reviewed on June 16, 2020, a total of 54,971 confirmed cases were reported nationwide for COVID-19, of which 5062 (9.2%) are cases in patients under 18 years of age.
In the nationwide analysis, the ages of the cases are dispersed, from 0 to 17 years in a homogeneous way, without any trend between age groups. Of these, 49% were male. In terms of clinical status, the majority were mild: 4022 cases (79.4%) and asymptomatic 854 cases (16.8%), the deceased cases were 8 (0.158%), registering a case fatality rate for pediatric patients in Colombia of 1.58 per 1000.
Regarding the place of attention and care of each case, it was found that the majority were at home 2886 patients (57%), only 26 cases in the (pediatric intensive care unit) (0.51%) and 146 in hospital (2.88%). Of the pediatric group, 1990 cases (39%) had been recovered until June 16, 2020. Only 18 imported cases from different nations were registered (Brazil, Chile, Egypt, Spain, United States, France, Jamaica, Mexico, United Kingdom and Dominican Republic), and all have been: asymptomatic or mild; therefore, the vast majority are related or under study (5044 cases).
A one-way ANOVA was conducted to determine if age means were different for groups with different clinical severity levels. Data are mean ± standard error. Subjects were classified into 5 groups, deceased (n = 8), severe (n = 26), moderate (n = 147), mild (n = 4022) and asymptomatic (n = 854).
There was a statistically significant difference between groups as determined by one-way ANOVA [F (5,5056) = 15.26, P < 0.001]. A Tukey post hoc test revealed that age was statistically significantly higher in the asymptomatic, compared with: deceased (6.5 ± 1.9 years, P < 0.009); severe (4.5 ± 1.1 years, P < 0.001); and moderate cases (3.1 ± 0.5 years, P < 0.001); moreover, age was statistically significantly higher in the mild, compared with: deceased (6.5 ± 1.9 years, P < 0.009); severe (4.5 ± 1.1 years, P < 0.001); and moderate (3.1 ± 0.5 years, P < 0.001) (Fig. 1).
;)
FIGURE 1.: Median age, interquartilic ranges, by clinical severity.
In contrast, the less severe groups: mild versus asymptomatic (0.01 ± 0.2 years, P = 1); and those of greater severity: moderate versus severe (1.4 ± 1.1 years, P =.830); or moderate compared with deceased (3.4 ± 1.9 years, P = 0.504), showed no differences (Table 2).
Table 2. -
Tukey’s Paired Comparison of the Means of Ages by Clinical Severity in Nationwide Analysis (See Text)
| Clinical Severity |
Mean Age |
Standard Error |
Significance |
| Asymptomatic |
9.38 |
0.18 |
B |
| Mild |
9.35 |
0.08 |
B |
| Moderate |
6.27 |
0.44 |
A |
| Severe |
4.88 |
1.05 |
A |
| Deceased |
2.89 |
1.90 |
A |
Different is at statistical significance at P > 0.05.
*Means sharing a letter are not significantly different at the 5% level.
Regarding ages, asymptomatic cases had a mean of 9.37 years, the mild ones 9.35 years, the moderate 6.27 years, the severe 4.88 years and the deceased 2.88 years. Likewise, the analysis by place of care reveals that the mean age of the cases that were at home was 9.4 years, recovered 9.4 years, in the hospital it was 6.1 years, in the intensive care unit (ICU) 4.9 years (Fig. 2).
FIGURE 2.: Median age, interquartilic ranges, by place of care.
Statistically significant difference determined with one-way ANOVA was found between groups (F = 16.08, P <0.001). Post hoc analysis reveals significant differences between groups, the age of patients at home (9.39 years) and those recovered (9.3 years) being significantly higher than those in ICU (4.9 years), in hospital (6.1 years), or than the deceased (2.9 years) (Table 3).
Table 3. -
Tukey’s Paired Comparison of the Means of Ages by Place of Care in the Nationwide Analysis (See Text)
| Clinical Attention |
Mean Age |
Standard Error |
Significance |
| Recovered |
9.38 |
0.12 |
B |
| Home |
9.40 |
0.10 |
B |
| Hospital |
6.20 |
0.44 |
A |
| ICU |
4.88 |
1.05 |
A |
| Deceased |
2.88 |
1.90 |
A |
Different is at statistical significance at P > 0.05.
*Means sharing a letter are not significantly different at the 5% level.
Most cases of pediatric patients have been registered in cities such as: Bogotá with 1874 (37%), followed by Barranquilla 485 (9.58%), and in terms of departments, the majority of cases are registered in Atlántico 1017 (20.1%), Valle 388 (7.6%), Bolívar 360 (7.11%) and others.
A regional analysis was performed among cities and departments with higher number of cases finding that, overall, of the analyzed regions, there was a statistically significant difference in age means between more severe (moderate, severe and deceased) and less severe cases (mild and asymptomatic) in the 3 most affected regions, however, with some particular differences. Moreover, the relationship between age and place of care was statistically significant for the comparison between groups with higher care requirements: Cases in hospital are younger than patients at home and those who are recovered.
In Bogotá, capital and most populated city in Colombia, 1874 cases of children under 18 years infected with COVID-19 were registered, 73.5% mild and 23.4% asymptomatic cases, and only 8 severe (0.4%). The majority, 1082 (57.7%) are at home and 736 (39.2%) are recovered, with no death record. In the other heavily affected regions, outbreaks of infection were evident in the cities and closest municipalities; however, in the analysis by regions, the infection is highly dispersed geographically, in central, coastal and even jungle regions, with no apparent determinants associated with contiguity or access roads.
Strikingly, in Amazonas, the south eastern department of Colombia, distant and without land access to the interior of the country, but with border with Brazil and Peru, 225 cases were registered, of minors under 18 years of age, infected with COVID-19, 94.2% of the cases registered in Leticia, which is the capital of the department, bordering the city of Tabatinga in Brazil which is hardly hit by COVID-19. Likewise, in Nariño, department in the south of Colombia, bordering Ecuador, 211 cases were registered, of which 53% of the cases were registered in Tumaco which is a town with a high number of internally displaced people,9,10 which generates greater difficulties in living conditions.
DISCUSSION
The population of Colombia for the year 2018 according to the national statistics department (DANE) was 48,254,494 people in the entire territory, of which the population from 0 to 19 years old corresponded to 15,113,307 inhabitants (31.32%). And those under 15 years old were 10,905,515 (22.6%).11 Therefore, until June 16, 2020, there were registered 3.35 cases for every 10,000 minors in Colombia. Without finding significant differences between genders, as has been observed in other studies in China, South Korea and Pakistan.12–14
Children are less affected by severe acute respiratory syndrome (SARS)-CoV-2, according to Chinese health authorities, who reported that of the 72,314 cases reported until February 2020, only 2% corresponded to children under the age of 19, in one of the reported series, none of the children had comorbid diseases, with mild to moderate symptoms in the vast majority (65%), only 9% were asymptomatic, unlike in adults, reaching 70% of asymptomatic.2,14–16 This agrees with the data found in this series of patients and could be the result of different factors such as less testing and less exposure.
In a systematic review, 444 cases of children younger than 10 years were found, 553 between 10 and 19 years old, 2 articles that described 2 newborns, 5 articles reported cases of infants, in patients with history of travel from Wuhan, China or contact with an infected family member.17,18 Most patients had good prognosis, including those who were in the ICU, and only registered 1 death in the population group 10–19 years of age.17 The Johns Hopkins Bloomberg School of Public Health study group showed that children are at similar risk to infection as adults, but that they have fewer symptoms,18,19 as shown by low rates of hospitalization, and admission to ICU of patients in Colombia.
Some countries that implemented tests more broadly, such as South Korea and Iceland, found that children were underrepresented. There were no COVID-19 positive children under 10 years of age in Iceland compared with 0.8% of the general population.17 In Italy, in the Vo municipality, a similar situation was recorded, tests were carried out on 86% of the population and no cases were found in children under 10 years, as compared with 2.6% of the general population.17 This differs in this series of children from Colombia, probably because of the social, economic characteristics and type of quarantine used in South Korea and Iceland.
Despite a large number of children living with adults with COVID-19, no large-scale nearby transmissions were detected, as recorded by Japan and Guangzhou, China, with a secondary contagion rate, much lower in children than in adults (odds ratio 0.23 compared with adults over 60 years).20 In another review of an international family cluster, it was found that children were not the index cases in family contact for COVID-19, only 10% of such clusters were started by a child, and in Guangzhou only 5%.21,22 A case study in the French Alps included a child with a positive COVID-19, who did not transmit this infection to anyone from his contacts, despite being exposed to more than 100 children in different schools and a ski resort.23 In the New South Wales region, Australia, none of the 735 students and 128 school staff members contracted COVID-19 from 9 children and 9 adults who were index cases and had close contact.24 In the Netherlands, primary care data and family contacts suggest that SARS-CoV-2 is mostly spread among adults and from adults to close children in their family.25 These descriptive clinical studies suggest that transmission from children to adults is at low risk.
The findings of this study suggest that, in Colombia, the child population is at low risk of complications, compared with the adult population; with a higher risk of serious illness, or requiring advanced medical attention, in younger children (6.27 years for moderate conditions and 4.88 years for severe), which is evident in this sample, with statistically significant differences in the age means comparing the most severe clinical states with the least severe.
Thus, the cases of children infected with COVID-19, positive by polymerase chain reaction are 9% of the total infected population in Colombia, which can be interpreted as a low risk compared with adults of contracting said virus, with mild symptoms in children (79.4%). According to the study by Zimmerman and Curtis,18 the frequency of positive COVID-19 cases in children in Colombia, is higher than in China and South Korea (n = 89,069) with 4.8% of children in the total confirmed cases.13,14 As well as in the United States, where they registered up to 1.7% of all cases, with less than 15% under 1 year old, 26% between 1 and 9 years old, 59% from 10 to 17 years old.19 Or in Pakistan, where the total number of confirmed cases as of May 3, 2020, according to the report of his government, was 20,084 and 457 (2.3%) died, of which 7.1% of cases are children with 0.6% of deaths.12,16
The infant mortality rate in Bogotá for 2019 was 9.6 per 1000 live births, and this rate is not affected by COVID-19 cases until June 16, 2020.26 For 2017, the rate of national infant mortality, reached 10.7 deaths per 1000 live births, if add to this mortality rate from COVID-19 in children until June 16, 2020 (0.33 per 1000), it would increase to 11.3 deaths per 1000 live births probably.11,27
Considering the infant mortality rate (in Colombia for 2005 and 2008) was 57.9% higher in the first quintile of poverty, with a concentration index of −0.083, that it is an inequality in favor of the most favored or better socioeconomically well-off, that could suggest, the least favored and with less socioeconomic access will have a higher risk of mortality from COVID-19 in all regions of Colombia.28,29 The majority of deaths in children, under 1 year of age have been considered inequitable because they were avoidable, unfair and unnecessary. Then, this suggest that this indicator reflects the health and development conditions of the countries, and shows the level of priority that governments give to the right to health.28
These low mortality data in Colombia are consistent with that described by Bhopal et al30,31 who examined mortality data from 0 to 19 years old, in France, Germany, Italy, South Korea, Spain, the United Kingdom and the United States, with a total of 44 deaths of COVID-19 at that age (total population: 135,691,226) at May 19, 2020. In a normal period of 3 months, in those countries, they found a global burden of disease rate, which showed more than 13,000 expected deaths, from all causes for that age, including nearly 1000 unintentional injuries and 308 lower respiratory tract infections including influenza. COVID-19, according to said estimate, was responsible for about 0.333% deaths between 0 and 19 years.32
The exact reasons for the difference between adults and children are still unknown. But they have been postulated that these can be explained by the immune function and the expression of the response of cellular receptors in the lungs, immunity with higher contact load in adults, constitutionally high lymphocyte count in children, could have a protective effect against the severity of SARS-CoV-2.8,16,30
The national unemployment rate in Colombia was 19.8% for April 2020.9 These could be associated risk factors: access to health, education and family protection in the most remote regions of urban areas and they carry a higher risk of contagion by COVID-19, in this situation of socioeconomic precariousness. The Colombian Ministry of Labor published in March 2013 that 25.3% of the displaced population of Nariño went to Tumaco, which is another aspect that increases risk of contagion with COVID-19,10 reflected in the greater number of cases of children with COVID-19 in this study and in that municipality of Colombia.
It would be likely to resume activity in minors, much more safely than in adults, given the previous international findings and our low frequency of cases in children, according to the results of this study. These findings could be used for developing public policies at the national level, and depending on the particularities of each region, the causes of these differences being less pronounced than when the country as a whole is analyzed.8,33 In addition, we can also affirm that the fact of generating an education of distancing, self-care, protection of the ages of greatest risk will decrease contagion and mortality risks, as we see in our children under 4 years of age according to the literature and our data.
CONCLUSIONS
Of the total of 54,971 positive cases for COVID-19 in Colombia, only 5062 cases were registered in patients under 18 years of age, 9.2% of the total registered patients, with no gender difference at this age.
The results of this study show that, at the national level, patients in more severe states (deceased, severe and moderate), are significantly younger than those in the milder state (asymptomatic and mild); likewise, in the analysis of the place of care, those who have died, the hospitalized, and those in the ICU are significantly younger than those at home or who have recovered. These findings suggest that, although in general, the risk of complications is low in children, those of younger age (6.27 years for moderate symptoms and 4.88 years for severe symptoms), are at significantly higher risk of suffering more severe clinical symptoms and requiring greater healthcare than older children. At the local level by region, this trend was maintained, although not always with statistical significance.
Most pediatric cases were registered in capital cities, with a large number of inhabitants, high unemployment rates, high rates of population displacement, some with a low level of population education and limitations in access to health, and extensive international borders, such as Amazonas (Leticia) or Nariño (Tumaco). The registration of COVID-19 cases should continue until the end of the pandemic, to obtain final data on its behavior in the Colombian pediatric population and thus obtain effective control measures and improvement of risk factors of our population.
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