Clinical Spectrum of COVID-19 in a Pediatric Mexican Population

doi:10.21203/rs.3.rs-81586/v1

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Clinical Spectrum of COVID-19 in a Pediatric Mexican Population

https://doi.org/10.21203/rs.3.rs-81586/v1

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published 22 Sep, 2020

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Objective: From the beginning of the COVID-19 pandemic, it has become evident that the spectrum of manifestations in children is different from those seen in adults. In this study, we aimed to describe a broader clinical spectrum of COVID-19 in children.

Methods: In this descriptive, prospective study, we enrolled confirmed pediatric patients with COVID-19 who presented to a pediatric tertiary care center from April to July 2020. All patients were confirmed by the SARSCoV-2 RT-PCR test, and we analyzed 24 symptoms and 25 signs.

Results: We analyzed 50 patients with COVID-19. From the evaluated signs and symptoms, the most common symptoms were fever, irritability and dry cough, digestive symptoms were frequently found (24%), and the most common signs were pharyngeal hyperemia and irritability.

Conclusion: Clinicians should recognize that the clinical spectrum of COVID-19 in children is wider than previously described. Although the classic signs and symptoms are frequent, digestive symptoms should raise suspicion.

COVID-19

children COVID-19

clinical spectrum

digestive symptoms

What this study adds?

The clinical spectrum of COVID-19 in children is wider than previously described. Although the classic signs and symptoms are frequent, digestive symptoms and other symptoms like loss of taste or sensation should raise suspicion. Some patterns of appearance of symptoms could predict poor outcomes.

The incidence of COVID-19 in Mexico began to escalate rapidly since April 2020. By July 31, Mexico had the third highest number of deaths by COVID-19 worldwide. By August 7, 12,052 cases of COVID-19 in children were confirmed in Mexico, with 188 deaths [1].

From the beginning of the COVID-19 pandemic, it has become evident that the spectrum of manifestations in children is different from those seen in adults. However, most of the clinical descriptions have been made from retrospective studies addressing a narrow number of manifestations. A meta-analysis [2] and a systematic review [3] evaluated less than ten signs and symptoms. The aim of this study was to describe a broader clinical spectrum of COVID-19 in children.

We conducted a prospective study in a pediatric tertiary care center from April to July 2020, following 24 symptoms and 25 signs in children. The information was gathered by attending physicians. We included patients <18 years, any gender, with history in the week before inclusion of at least one of the following criteria: a) one respiratory symptom, b) one gastrointestinal symptom or c) fever and recent exposure to a COVID-19 confirmed case. Patients with tracheostomy, severe neurologic underlying condition, use of sedatives in the last week or children not accompanied by the primary caretaker were excluded. All cases were tested with SARS-CoV-2 reverse-transcriptase-polymerase-chain-reaction of nasopharyngeal swabs. The information was analyzed using case counting and descriptive statistics, calculating median, ranges, quartiles and percentages. To analyze the sequence of appearance of symptoms prior to hospital arrival, we performed graphs for each patient showing the time of onset of each symptom. We defined pneumonia as one or more of the following manifestations: a) respiratory distress, b) oximetry <93% or cyanosis, c) hypoventilation in the chest examination, e) fine rales in the auscultation.

We evaluated 92 patients, finding 50 with confirmed COVID-19 infection by a positive SARS-CoV-2 RT-PCR test. Since chronic patients may have different clinical manifestations, they were described separately from previously healthy patients. (Tables 1 and 2).

Twenty-six patients with confirmed COVID-19 infection had a previous chronic medical condition. The most common underlying condition was cancer (16% of the patients), followed by chronic lung disease (12%), obesity (8%), chronic kidney disease (6%) and neurological disorders (4%). Three patients had more than one chronic condition.

From the evaluated signs and symptoms, the most common symptoms were fever, irritability and dry cough, and the most common signs were pharyngeal hyperemia and irritability. We found that digestive symptoms were common (24% of our patients), and we also found hyposmia in 4% of the patients. All patients without any respiratory or gastrointestinal symptoms were immunocompromised.

The first symptom to appear was fever in 36% of the cases and cough in 12%, followed by asthenia, rhinitis, and irritability in 8% of the patients. Manifestations intentionally sought but not found in any patient were expectoration, mucopurulent rhinorrhea, posterior nasal discharge, mucopurulent conjunctival discharge, and epistaxis. Manifestations intentionally sought that were found in only one patient were nasal mucosa edema, rhonchi, cyanosis, lymphadenopathy, thick rales, and wheezing.

Analyzing the symptom appearance sequence prior to hospital arrival, we defined three different patterns:

Pattern “A” or almost asymptomatic: with only one or two symptoms.

Pattern “S” or sudden: onset of four or more symptoms in the first 24 to 36 hours.

Pattern “D” or disperse: sequential onset of symptoms over several days.

The patterns were distributed in an irregular form in both groups; nonetheless, considering only the patients with pneumonia, the “S” pattern was found in seven of nine of the chronically ill patients, in three of eight immunocompromised patients, in four of the five patients with chronic lung disease and in three of four obese patients.

The rate of admission was significantly higher in chronically ill (61.5%) versus healthy individuals (31.7%); however, seven of the twenty-six chronically ill individuals were admitted for previous disease decompensation. Of the eight immunocompromised patients, three developed pneumonia. Four of the five patients with obesity also developed pneumonia

All patients with pneumonia except one were admitted. Only one patient developed Kawasaki-like syndrome. Two patients required mechanical ventilation: one of them was a patient with cystic fibrosis and the other was a kidney transplant patient who died.

Previous prospective reports on the clinical features of COVID-19 in children are scarce and sought a limited number of signs and symptoms. A broader description of the disease is of paramount importance for the clinical diagnosis and the decision to perform a SARSCoV-2 RT-PCR test. This is particularly important in low-income countries with limited access to the test. Although our study included a limited number of patients, it explored a wider clinical spectrum in a heterogeneous population of pediatric patients.

The testing capacity for SARS-CoV-2 in Mexico is limited and reserved for patients who meet the national epidemiological definition. Many children with symptoms consistent with COVID-19 in the community are not tested and consequently not diagnosed. Our inclusion criteria allowed us to analyze patients who otherwise would not have been tested. These results may serve to reconsider epidemiological definitions for children with suspected COVID-19.

It is important to highlight that this study captured data from children who were seen or managed within a tertiary health-care institution; one-half of the patients had a chronic medical condition. Consequently, the study population is likely to primarily represent individuals with the more severe end of the disease spectrum. Statistical differences between the two groups were not calculated since the research was designed as case series description, the sample is small and there is wide difference in age between both groups.

Adult patients with digestive symptoms without respiratory symptoms are rare [4], while in children, it seems to be more frequent. Our results suggest that even though classic respiratory signs and symptoms are frequent in children, digestive symptoms should raise suspicion of COVID-19 infection.

Loss of taste and smell in adults has been reported in up to half of patients [5] and proposed as an important discriminatory symptom. Chemosensory dysfunction in children is seldom reported [6], but our results suggest that both hyposmia and dysgeusia are not so rare.

Pneumonia in patients with COVID-19 has been reported in up to 64.9% of children with COVID-19 using radiologic criteria [7], but it is rarely reported using clinical criteria. We found one-third of patients with pulmonary infection exploring only clinical features.

The recognition of different clinical patterns of COVID-19 may help us recognize patients with a higher risk of poor outcomes. Our results suggest that the “S” or sudden pattern is associated with pneumonia in patients with underlying chronic conditions. Additionally, as shown in young adults [8], obesity appears to be an important risk factor for poor outcomes (pulmonary involvement) in children with COVID-19.

Clinicians should recognize that the clinical spectrum of COVID-19 in children is wider than previously described and different from the adult presentation; even though the classic signs and symptoms are frequent, digestive symptoms should increase clinical awareness. The order of appearance of symptoms (clinical pattern) requires more investigations, as our results suggest that it could predict outcomes.

Authors’ Contributions: EB conceptualized the study design. EB, DC, NS, MC recruited patients and collected demographic and clinical data. EB and DC analyzed and interpreted the results. EB wrote the manuscript in Spanish, NS, DC translate the manuscript. DC, NS, MC EB commented on and revised the manuscript. All authors approved the final report.

This work should be attributed to: Emergency Department, Hospital Infantil de México Federico Gomez

Disclaimer: Authors assume all responsibility for the information published.

There was no source of financial support.

Authors declare no conflicts of interest.

Status of ethical clearance: The study was approved by the ethics committee.

Dirección general de epidemiología, Secretaria de Salud. Available from: https://www.gob.mx/salud/documentos/datos-abiertos-bases-historicas-direccion-general-de-epidemiologia. Accessed September 11, 2020.
Zhang L, Peres TG, Silva MVF, Camargos P. What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. Pediatr Pulmonol. 2020;55:2115–27.
Liguoro I, Pilotto C, Bonanni M, Ferrari ME, Pusiol A, Nocerino A, et al. SARS-COV-2 infection in children and newborns: a systematic review. Eur J Pediatr. European Journal of Pediatrics; 2020;179:1029–46.
Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: A descriptive, cross-sectional, multicenter study. Am J Gastroenterol. 2020;115:766–73.
Chi H, Chiu N-C, Peng C-C, Lin C-H, Tai Y-L, Lee M-D, et al. One-Seventh of Patients with COVID-19 Had Olfactory and Gustatory Abnormalities as Their Initial Symptoms: A Systematic Review and Meta-Analysis. Life. 2020;10:158.
Mak PQ, Chung KS, Wong JSC, Shek CC, Kwan MYW. Anosmia and Ageusia: Not an Uncommon Presentation of COVID-19 Infection in Children and Adolescents. Pediatr Infect Dis J. 2020;39:E199–200.
Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med 2020; 382:1663-1665.
Steinberg E, Wright E, Kushner B. In Young Adults with COVID-19, Obesity Is Associated with Adverse Outcomes. West J Emerg Med. 2020;21:752–5.

Alternate versions of Table 1 and Table 2 are provided as downloads in the supplemental information.

Table 1. Signs and Symptoms among 50 Pediatric Patients

SYMPTOMS	Number (%)	SIGNS	Number (%)
Time of onset of symptom*	72 (33-144)
Fever	35 (70)	Pharyngeal hyperemia	30 (60)
Irritability	18 (36)	Irritability	12 (24)
Dry Cough	18 (36)	Rhinorrhea	10 (20)
Rhinitis	13 (26)	Conjunctival hyperemia	10 (20)
Sore throat	12 (24)	Respiratory distress	6 (12)
Headache	11 (22)	Dehydration	6 (12)
Abdominal pain	11 (22)	Fine rales	4 (8)
Conjunctivitis	11 (22)	Fever	4 (8)
Vomiting	11 (22)	Rash	3 (6)
Diarrhea	11 (22)	Hypoventilation	3 (6)
Shortness of breath	10 (20)	Rhonchi	2 (4)
Fatigue	9 (18)	Nasal mucosa hyperemia	2 (4)
Hyporexia	9 (18)	Dysphonic	2 (4)
Myalgia	7 (14)	Hyperemia of pillars	2 (4)
Dysgeusia	4 (8)	Somnolence	2 (4)
Arthralgia	4 (8)
Productive cough	4 (8)	KIND OF SYMPTOMS
Rash	4 (8)	Only respiratory	25 (50)
Hoarseness	5 (5)	Only gastrointestinal	12 (24)
Hypersomnia	3 (6)	Both	10 (20)
Hyposmia	2 (4)	Without any of them	3 (6)
Cyanosis	2 (4)

**Median (IQR) time from admission to onset of first symptom, hours

Table 2. Demographic Characteristics, Outcome Previous Treatment, and Clinical Patterns among 50 pediatric patients

	Chronic medical illness (N=26)	Previously healthy (N=24)	Total (N=50)
Age months, median (IQR)	108 (26-153)	18 (7.25-99.5)	56.6 (13-159)
Sex male, n (%)	20 (76.9)	15 (62.5)	35 (70)
Immunosuppression*, n (%)	8 (30.8)	0 (0)	8 (16)
Pneumonia*, n (%)	9 (34.6)	10 (41.7)	19 (38)
Admitted, n (%)	16 (61.5)	9 (37.5)	25 (50)
Previous Antibiotic treatment, n (%)	7 (26.9)	4 (16.7)	15 (30)
Previous Symptomatic treatment, n (%)	19 (73.1)	16 (66.7)	35 (70)
CLINICAL PATTERNS
Pattern “A”(almost Asymptomatic), n (%)	4 (15.4)	7 (29.1)	11 (22)
Pattern “B” (sudden), n (%)	12 (50)	9 (37.6)	21 (42)
Pattern “D” (disperse), n (%)	8 (30.8)	10 (38.8)	18 (36)

table1.jpg
Alternate version of Table 1 provided in the manuscript
Table2.jpg
Alternate version of Table 2 provided in the manuscript

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Journal Publication

published 22 Sep, 2020

Read the published version in Indian Pediatrics →

Version 1

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Clinical Spectrum of COVID-19 in a Pediatric Mexican Population

Status:

Journal Publication

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Abstract

Research Brief

Introduction

Methods

Results

Discussion

Declarations

References

Tables

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