Clinical Characteristics and Long Term Impact on Pediatric COVID-19 in Taiwan

Clinical Characteristics and Long Term Impact on Pediatric COVID-19 in Taiwan

This project will study severe COVID-19 related factors, host genes, biomarkers, and prognosis of severe encephalitis in children, and conduct:

1. Retrospective clinical analysis of children with COVID-19, to analyze the clinical manifestations of children with new crown infection, and to find the relevant factors of severe disease.
2. Prospective acceptance in the acute phase: mainly to understand the correlation between the interaction of host factors, viruses and microorganisms and the severity.
3. Children's long COVID-19 Tracking Team An integrated outpatient clinic for "Long COVID-19 Syndrome in Children" will be established to conduct systematic tracking of body, lung function, nerves and psychology. Children with neurological complications or other confirmed diagnoses will undergo physical, neurological, pulmonary function and brain MRI and neurophysiological examinations, sleep examinations, and conduct psychiatric clinical diagnostic interviews to establish a psychiatric diagnosis. Status and family social function, the intelligence development status was examined by intelligence test, and cognitive function was measured by neuropsychological test. Understand the microbial phase, immune function and incidence of allergic diseases after long-term new coronavirus infection.
4. Seroepidemiological Study Group Exploring the seroepidemiology of different groups of health care workers and non-health care workers will allow us to better understand the magnitude of natural infection among children and age groups in the community and the infection profile of health care workers during this period.

This trial includes multiple groups of prospective cases to explore the impact of the new coronavirus on children and the mechanism of severe illness, and integrates various specialties and branches of the Children's Hospital to conduct a summary trial, which is expected to understand children's new crown and community epidemiology, children infected with new crown Clinical manifestations of the virus, risk factors and effects on various systems, combined with host microbiome, immune function analysis and whole-exome sequencing, to improve the detection of new coronavirus (including long-term new coronary syndrome and pediatric multisystem inflammatory syndrome). Mechanisms of host factors and interactions with microbes to improve outcomes and severe incidence in children.

1. "Clinical Characteristics of pediatric COVID-19）" by the retrospective research group

   • Subject inclusion criteria: COVID-19 positive cases younger than 18 years old from January 1, 2020 to June 13, 2022.
   • Subject exclusion conditions: (none) The number of people to be included is expected to be 3000, and a retrospective case study data collection will be conducted.

2. Prospective case receiving group: divided into four groups: "acute case receiving group" (including children with multisystem inflammatory syndrome), "children's long COVID-19 tracking group", "seroepidemiological research group", "healthy control group" ", in which the "Acute Case Receipt Team" will simultaneously accept cases in Hsinchu and Yunlin Branches.

1. "Acute Receiving Group" (including children with multisystem inflammatory syndrome)

• Subject inclusion conditions: Novel coronavirus positive sick children younger than 18 years old
• Subject exclusion conditions: (none) The above is expected to be included in the number of 200 people will carry out the following (A) Complications caused by new coronavirus infection such as pneumonia (Pneumonia), Multisystem Inflammatory Syndrome in Children (MIS-C), encephalitis (Encephalitis), croup (Croup), sepsis (Sepsis), acute Respiratory distress syndrome (ARDS) and other host gene studies (Host factors) by whole exome sequence (WES).

(B) Testing the respiratory tract, intestinal tract, and central nervous system of 2019-nCoV, microbiota, host inflammatory biomarkers (biomarker: CRP, procalcitonin, DIC profiles…), serum antibody titers and antibody library/ Cell receptor library (spike specific B cell repertoire and T cell repertoire), chemokines (chemokines), cytokines (cytokines: IL-6...), cell-regulated immune response, epitope mapping, immune function test (such as IgG, IgA, IgM, Lymphocyte subset...), host transcriptome research. (see table below) (C) Patients with neurological complications will undergo neurological, pulmonary function, brain MRI and neurophysiological examinations, as well as brain injury biomarkers (Biomarker) changes in acute and chronic phases. (see table below) (D) Physiological monitor of heart rate variability or ECG signal collection over 7 to 14 days and compared with recovery period signal.

(E) Abdominal ultrasound and other tests will be performed for those with abnormal liver function.

(F) Related tests for acute renal failure (CBC+DC, BUN/creatinine/uric acid/Na/K/Cl/LDH/blood gas and urinalysis)

2. "Children's long COVID-19 Tracking Group"

• Subject inclusion conditions: COVID-19 positive cases
• Exclusion conditions for subjects: It is necessary for those who are not suitable to perform "MRI". If there is a metal substance that cannot be removed from the body or a serious disease cannot cooperate with this examination, it is necessary to avoid unexpected occurrences when performing "MRI". Risk considerations, sensory or motor impairments and pregnancy are also inconvenient to perform MRI. For the purpose of the study, those with other causes of encephalitis or those with hypoxic conditions that may affect the cognitive function of the brain are also included in the exclusion conditions in order to avoid errors in the interpretation of the test results.

Exclusions: Anyone who has any of the following conditions cannot participate in this study:

1. You have metal substances that cannot be removed or implanted, such as: braces, metal nails, artificial electronic ears, heartbeat pacemakers, etc. Because of the inability to perform brain MRI, it is not suitable to participate in this trial.
2. Have major physical diseases.
3. Sensory impairment, such as deafness.
4. Movement disorders, such as cerebral palsy.
5. Uncontrolled and stable epilepsy.
6. Pregnant women are not suitable to participate in this test. (If you are pregnant or not sure if you are pregnant, please let the researcher know in advance so that a pregnancy test can be performed).
7. Those who have suffered from hypoxia due to encephalitis or other reasons not caused by enterovirus infection are not suitable to participate in this test.

The number of people expected to be included above is 1,000, and the following will be carried out (A) Establish an integrated outpatient tracking of "Long COVID-19" to conduct systematic tracking of body, lung function, nerves, and psychology. Children with neurological complications or other confirmed diagnoses will undergo physical, neurological, pulmonary function and brain MRI and neurophysiological examinations, sleep examinations, and conduct psychiatric clinical diagnostic interviews to establish a psychiatric diagnosis. Status and family social function, the intelligence development status was examined by intelligence test, and cognitive function was measured by neuropsychological test.

(B) Microbial phase, immune function and incidence of allergic diseases after long-term 2019-nCoV infection.

3. "Seroepidemiological Research Group"

• Subject inclusion conditions:

  1. Voluntarily join the medical staff receiving blood draws. The medical staff of National Taiwan University Hospital, including physicians, nurses, administrative staff, research assistants, cleaning and delivery staff, etc., receive cases in groups according to age. 20-29, 30-39, 40-49, 50-59, and over 60 years old, each group received 60 cases, a total of 300 people. Voluntary participation in non-medical staff receiving blood draws.
  2. The general public who solicited voluntary non-medical workers from the community, received 60 cases in each group of 0-9, 10-19, 20-29, 30-39, 40-49, 50-59, and over 60 years old. people, a total of 420 people.

• Subject exclusion conditions: those who are unwilling to accept blood draws. The above is expected to include 720 people. "Seroepidemiology of novel coronavirus" will be performed, and blood will be drawn three times, once after consent and once after 3 months and 6 months.

• COVID-19 antibody test Serum samples will be tested with commercially available validated test kits, such as Roche's Elecsys Anti-SARS-CoV-2 Assay (Roche Molecular System Inc., CA, USA). Antibodies tested include anti-S and anti-N antibodies. Verify by in-house ELISA or Western blot if necessary.

  4. "Healthy Control Group"

• Inclusion criteria for subjects: "No" healthy individuals with complications after new coronavirus infection or long-term new coronary syndrome Test the respiratory tract and intestinal microbiota (Microbiota), host inflammatory biomarkers, serum antibody titers and antibody library/receptor library of novel coronavirus, chemokines, cytokines, and cell-regulated immunity in healthy control groups Response, epitope mapping, brain MRI, neurophysiological examination (nerve conduction, brain wave, sleep watch examination, etc.), brain injury biomarkers (biomarker), host transcriptome research

• Subject exclusion conditions: (none) The above is expected to include 200 people, and the "acute receiving group" will be matched with the same sex and a normal control group of plus or minus 1 year old.

Inclusion Criteria:

• COVID-19 positive cases

Exclusion Criteria:

1. You have metal substances that cannot be removed or implanted, such as: braces, metal nails, artificial electronic ears, heartbeat pacemakers, etc. Because of the inability to perform brain MRI, it is not suitable to participate in this trial.
2. Have major physical diseases.
3. Sensory impairment, such as deafness.
4. Movement disorders, such as cerebral palsy.
5. Uncontrolled and stable epilepsy.
6. Pregnant women are not suitable to participate in this test. (If you are pregnant or not sure if you are pregnant, please let the researcher know in advance so that a pregnancy test can be performed).
7. Those who have suffered from hypoxia due to encephalitis or other reasons not caused by enterovirus infection are not suitable to participate in this test.