Clinical and Immunological Characterisation of COVID-19 in Children, Adolescents and Adults

Study Overview
=================
Brief Summary
-----------------
The investigators aim to characterise Coronavirus Disease 2019 (COVID-19) in every age group. On the one hand, emphasis is put on the initial presentation, clinical course, outcome and the therapy used. On the other hand further investigations regarding viral and bacterial coinfections, and response of the immune system will be conducted. This study should serve to improve the understanding of COVID-19, to identify risk factors for a severe clinical course and to obtain further insights into pathophysiology of this new infectious disease.

Detailed Description
-----------------
In 2019 the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen causing the Coronavirus Disease 2019 (COVID-19) pandemic. Many retrospective studies have been conducted regarding clinical signs and symptoms and clinical course of the disease. In most cases the infection causes only light symptoms of the upper respiratory tract. The infection can also be asymptomatic. However, in some the disease can cause a severe infection of the lower respiratory tract leading to acute respiratory syndrome (ARDS) which can be fatal. Especially elderly people suffer from severe disease whereas children are less compromised. In this prospective, monocentric study the investigators include patients of all ages with COVID-19 and also a control group of all ages with respiratory tract infections other than COVID-19. Initial presentation, clinical course, outcome and the therapy used will be recorded. Standard diagnostic procedures (vital signs, results of blood samples, blood gas analysis, x ray, ct scan) will also be recorded. To further characterise the study population naso- and oropharyngeal swabs will be checked for viral and bacterial coinfections. The SARS-CoV-2 viral load will be estimated. To characterise the immunological response IgM- and IgG-antibodies for SARS-CoV-2 will be measured. Moreover lymphocyte typing, cytokine and chemokine analysis will be conducted. The investigators will also include an analysis of the proteome in serum and urine. To characterise the virus-host-interaction HLA analysis of the patients will be conducted. In the case of a medically indicated bronchoscopy bronchoalveolar lavage will be analysed in regards of viral load, coinfections, lymphocyte typing and cytokines / chemokines. In case of a medically indicated lung biopsy or in a post mortem lung biopsy a histological analysis will be made. In general, samples will be analysed at the initial presentation and after two weeks. Further analysis will be conducted depending on special events like clinical deterioration. Long-term follow up will be ensured by telephone visits.

Official Title
-----------------
Clinical and Immunological Characterisation of COVID-19 in Children, Adolescents and Adults

Conditions
-----------------
COVID-19, SARS-CoV-2

Intervention / Treatment
-----------------
* Other: this study is non- interventional


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with COVID-19: detection of SARS-CoV-2 by PCR in naso- or oropharyngeal swab or sputum, no age limit control group: any respiratory tract infection not caused by SARS-CoV-2, no age limit informed consent Exclusion Criteria: no respiratory tract infection and no detection of SARS-CoV-2 no informed consent
Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children and Adolescents with COVID-19<br>age range: newborn - 18 years old, subgroups will be established | Other: this study is non- interventional<br>* this study is non- interventional<br>|
| Adults with COVID-19<br>age range: from 18 years old, subgroups will be established | Other: this study is non- interventional<br>* this study is non- interventional<br>|
| Control group<br>all ages, any respiratory tract infection, subgroups will be established | Other: this study is non- interventional<br>* this study is non- interventional<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical course of COVID-19 | Description of clinical course of COVID-19 in children, adolescents and adults | 10/2020 | 
| Analysis of development of antibodies to SARS-CoV-2 | Measurement of specific IgM- and IgG-antibody production | 10/2020 | 
| Estimation of viral load | Estimation of viral load at initial presentation and after two weeks | 10/2020 | 
| Detection of viral coinfections | A Multiplex PCR will be conducted to test for the most common respiratroy viruses. A naso- and oropharyngeal swab will be used for this | 10/2020 | 
| Measurement of cytokine and chemokine response | Determination of cytokine and chemokine concentrations in serum by ELISA. | 12/2020 | 
| Characterisation of virus-host-interaction | Characterisation of virus-host-interaction by HLA-typing | 12/2020 | 
| Identification of disease patterns in proteome | Identification of disease patterns in proteome by analysis of the proteome in serum and urine | 12/2020 | 
| Analysis of change in lymphocyte subtypes | Detection of change in lymphocyte subtypes in blood and bronchoalveolar lavage | 10/2020 | 
| Analysis of histological changes in severe lung disease | Analysis of histological changes in severe lung disease by lung biopsy | 12/2020 | 
| Detection of bacterial coinfections | A pharyngeal swab will be cultured to check for bacteria residing in the upper airways. Additionally, a blood culture will serve to detect bacteremia | 10/2020 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, SARS-CoV-2