COVID-19 in Immunosuppressed Children

Study Overview
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Brief Summary
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Viral respiratory infections are common infectious complications after kidney transplantation, especially in the pediatric age group, and immunosuppressed patients may develop more severe disease. Immunosuppressive medications alter the patient's immune response by acting on humoral, cellular immunity and neutrophil function, increasing the risk of serious viral infections. Little is known about how these patients respond to infection by the new coronavirus (SARS-CoV-2). Experience with SARS caused by the Influenza H1N1 virus suggests that the severity of the disease depends on pre-existing comorbidities and the individual immune response. In more severe cases, an imbalance between the inflammatory system and the immune system is observed, determining direct consequences when pro and anti-inflammatory cytokines reach the systemic circulation in an exacerbated and unbalanced manner. Such fact can generate cytokine storm syndrome, resulting in multiple organ dysfunction syndrome. March 2020 reports from Papa Giovanni XXIII Hospital in Bergamo, Italy - one of the largest pediatric liver transplant centers - showed that the number of transplant patients infected with Coronavirus disease 2019 (COVID- 19) increased progressively. However, they did not see greater severity and complications in this population. Immunosuppression could act as a protective factor. The present study aims to describe the prevalence of viral infection by SARS-CoV-2 in a sample of immunosuppressed children, from three groups: kidney transplants, liver transplants and oncohematological. The investigators will also look for the epidemiological profile and clinical evolution of these patients, enabling a better understanding of the COVID-19 in this special population. The investigators' hypothesis is that infection with the new coronavirus may be asymptomatic in a large number of children and that immunosuppression, observed in liver and kidney transplant patients and also seen in cancer patients, may act as protection for severe forms of COVID-19. After obtaining written informed consent from the family, the investigators will include patients from 0-18 years of age, on regular outpatient follow-up, symptomatic or not, and will check for the presence of IgM/IgG antibodies against the SARS-CoV-2. For those symptomatic or with a positive IgM result, material (oro/nasopharyngeal swabs) for RT-PCR trial for the new coronavirus will be collected. Demographic and clinical variables will be registered. The outcomes are: Serology for COVID-19 result; PCR for COVID-19 result; presence of symptoms of COVID-19; proportion of patients with viral shedding on days 3,7,14,21 and 30 after diagnosis; need for hospital admission; need for Intensive care admission; death.

Detailed Description
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Variables to be measured Demographic data (initials, record, age, sex, race / ethnicity, weight, height, BMI). Epidemiological data: For kidney transplant patients: time of transplant, in years and complete months; primary kidney disease; presence and time of onset of respiratory symptoms, in days; presence of risk factors or comorbidities; current immunosuppression (drugs and doses); serum level of calcineurin inhibitor on the day of collection; previous vaccination for Influenza; previous viral infections; date of the last episode of rejection treated. For liver transplant patients: time of transplant, in years and complete months; primary liver disease; presence and time of onset of respiratory symptoms, in days; presence of risk factors or comorbidities; current immunosuppression (drugs and doses); serum level of calcineurin inhibitor on the day of collection; previous vaccination for Influenza; previous viral infections; date of the last episode of rejection treated. For oncohematological patients: time of diagnosis, in years and complete months; primary oncohematological disease; treatment received for the oncohematological disease; presence and time of onset of respiratory symptoms, in days; presence of risk factors or comorbidities; current cancer treatment; previous vaccination for Influenza; previous viral infections. Clinics visit / hospitalization data: clinical picture: syndromic diagnosis / signs and symptoms; initial image exam: chest X-ray and / or chest CT; Treatment performed: antiviral, antibiotic, corticoid (reason / dose / time); respiratory support (oxygen therapy only / Non-Invasive Ventilation / High Flow Nasal Cannula / invasive mechanical pulmonary ventilation / ECMO - time of use (days); days free of oxygen therapy, Non-Invasive Ventilation and invasive mechanical pulmonary ventilation. Diagnosis of SARS-CoV-2 infection: rapid test for Covid-19 in the blood: IgM / IgG; rapid test for COVID-19 in nasopharyngeal or tracheal secretion. Outcomes: Serology for COVID-19 result; PCR for COVID-19 result; presence of symptoms of COVID-19; proportion of patients with viral shedding on days 3,7,14,21 and 30 after diagnosis; need for hospital admission; need for Intensive care admission; death.

Official Title
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COVID-19 in Immunosuppressed Children

Conditions
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Infections, Coronavirus, Kidney Transplantation, Liver Transplantation, Cancer, Covid19

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal or liver transplant patients, with functioning graft and using immunosuppression, in outpatient follow-up or hospitalized. Patients treating oncohematological disorders, in outpatient follow-up or hospitalized.. Exclusion Criteria: Patients who or whose parents refuse to sign the Informed Consent Form.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Kidney transplant patients<br>Patients submitted to kidney transplantation. | |
| Liver transplant patients<br>Patients submitted to liver transplantation. | |
| Oncological patients<br>Oncological patients submitted to chemotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serology (IgM, IgG) for COVID-19. | percentage of positivity | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital admission | percentage of patients admitted to hospital | 9 months | 
| Intensive care admission | percentage of patients admitted to intensive care unit | 9 months | 
| Death | percentage of patients who died | 9 months | 
| Positive PCR for COVID-19 | percentage of positivity | 9 months | 
| Clinical characteristics of patients with COVID-19 | Percentage of patients with symptoms of COVID-19 | 9 months | 
| Proportion of patients with viral excretion in respiratory secretion and faeces on days 3, 7, 14, 21 and 30 after confirmation of covid 19. | Percentage of patients with positive PCR in respiratory secretion and feces on days 3, 7, 14, 21 and 30 after confirmation of covid 19. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Kidney transplantation, Liver transplantation, Cancer, Children, Adolescents, Pediatrics