Host-pathogen Interactions During SARS-CoV-2 Infection

Not Applicable

Completed

• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2; Infection, Coronavirus
• Interventions: Biological: Blood sample; Biological: Low or upper respiratory tract sample; Biological: Stool collection or fecal swab; Other: phone call

• Registration Number: NCT04376476
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

The new Severe acute respiratory syndrome coronavirus (SARS-CoV-2) named coronavirus disease 2019 (COVID-19) is currently responsible for a pandemic spread of febrile respiratory infections, responsible for a veritable global health crisis.

In adults, several evolutionary patterns are observed: i) a/pauci-symptomatic forms; ii) severe forms immediately linked to rare extensive viral pneumonia; and iii) forms of moderate severity, some of which progress to secondary aggravation (Day 7-Day 10). Children can be affected, but are more rarely symptomatic and severe pediatric forms are exceptional.

Like some other coronaviruses (SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV)), these differences in clinical expression could be based on a variability in the immunological response, notably either via inhibition of the type I interferon (IFN-I) response, or on the contrary an immunological dysregulation responsible for a "cytokine storm" associated with the aggravation. Little is known about the impact of these innate immune response abnormalities on the adaptive response. In addition, certain genetic factors predisposing to a state of "hyper-fragility" and certain viral virulence factors could also be predictive of the clinical response.

In this context, the main hypothesis is that the virological analysis and the initial biological and immunological profiles are correlated with the initial clinical presentation of COVID-19 infection. In particular, children forms and pauci-symptomatic disease in adults may be linked to a more robust innate immune response, including better production of IFN-I.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-28
• Study Start: 2020-05-05
• Study First Submitted QC: 2020-05-05
• Study First Posted: 2020-05-06
• Primary Completion: 2022-05-13
• Study Completion: 2022-05-13
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-04
• Last Update Posted: 2023-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Group E1:

• Age from birth to <18 years old;
• Weight> 3 kilogram (kg);
• Infection with SARS-CoV-2 virus confirmed by RT-PCR on upper respiratory tract sample
• No fever or respiratory symptoms;
• Not requiring hospitalization (or hospitalization not related to a SARS-CoV-2 infection);
• Consent signed by at least one parent / holder of parental authority and assent of the child (if applicable);
• Beneficiary of a social security scheme

Group E2:

• Age from birth to <18 years old;
• Weight> 3kg;
• Infection with the SARS-CoV-2 virus confirmed by RT-PCR on a upper or low respiratory tract sample or pneumonia with scanner suggesting SARS-CoV-2 infection;
• Hospitalized in a pediatric intensive care unit or in a general pediatrics unit
• Consent signed by at least one parent / holder of parental authority and assent of the child (if applicable);
• Beneficiary of a social security scheme

Group E3:

• Age from birth to <18 years old;
• Weight> 3 kg;
• Negative SARS-CoV-2 PCR on at least one respiratory sample, and other confirmed viral infection
• Hospitalized in a pediatric intensive care unit or in a general pediatrics unit, for a respiratory reason;
• Consent signed by at least one parent / holder of parental authority and assent of the child (if applicable);
• Beneficiary of a social security scheme

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Exclusion Criteria

Group E1:

• Patients with any other inherited or acquired immune deficiency that could compromise the immunological evaluation;
• Other Suspected or proved infection
• Pregnancy.

Group E2:

• Patients with any other inherited or acquired immune deficiency that could compromise the immunological evaluation;
• Pregnancy.

Group E3:

• Patients with any other inherited or acquired immune deficiency that could compromise the immunological evaluation;
• Infection with the SARS-CoV-2 virus known among the relatives
• Pregnancy.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Children group E1	Blood sample	Children with confirmed asymptomatic or pauci-symptomatic COVID infection will be recruited in pediatric emergency departments, among siblings of COVID-19+ pediatric patients or through the blood collection centers set up by the occupational health services. A single visit will be scheduled at the hospital (for clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E2	Stool collection or fecal swab	Children with confirmed COVID-19 infection requiring hospitalization will be recruited within participating centers (mostly in emergency and intensive care units). Data will be recorded (clinical examination, biology, immunology, virology measurements) during their hospital stay (day 0, day 7, in case of worsening) and a phone call performed at day 14 (or onsite visit if patient still hospitalized).
Children group E1	Low or upper respiratory tract sample	Children with confirmed asymptomatic or pauci-symptomatic COVID infection will be recruited in pediatric emergency departments, among siblings of COVID-19+ pediatric patients or through the blood collection centers set up by the occupational health services. A single visit will be scheduled at the hospital (for clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E1	phone call	Children with confirmed asymptomatic or pauci-symptomatic COVID infection will be recruited in pediatric emergency departments, among siblings of COVID-19+ pediatric patients or through the blood collection centers set up by the occupational health services. A single visit will be scheduled at the hospital (for clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E2	Blood sample	Children with confirmed COVID-19 infection requiring hospitalization will be recruited within participating centers (mostly in emergency and intensive care units). Data will be recorded (clinical examination, biology, immunology, virology measurements) during their hospital stay (day 0, day 7, in case of worsening) and a phone call performed at day 14 (or onsite visit if patient still hospitalized).
Children group E3	phone call	Children with confirmed non-COVID-19 viral infection requiring hospitalization will be recruited within participating centers (mostly in intensive care units). At inclusion, data will be recorded (clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E2	Low or upper respiratory tract sample	Children with confirmed COVID-19 infection requiring hospitalization will be recruited within participating centers (mostly in emergency and intensive care units). Data will be recorded (clinical examination, biology, immunology, virology measurements) during their hospital stay (day 0, day 7, in case of worsening) and a phone call performed at day 14 (or onsite visit if patient still hospitalized).
Children group E3	Low or upper respiratory tract sample	Children with confirmed non-COVID-19 viral infection requiring hospitalization will be recruited within participating centers (mostly in intensive care units). At inclusion, data will be recorded (clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E3	Blood sample	Children with confirmed non-COVID-19 viral infection requiring hospitalization will be recruited within participating centers (mostly in intensive care units). At inclusion, data will be recorded (clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.
Children group E3	Stool collection or fecal swab	Children with confirmed non-COVID-19 viral infection requiring hospitalization will be recruited within participating centers (mostly in intensive care units). At inclusion, data will be recorded (clinical examination, biology, immunology, virology measurements) and a phone call performed at day 14.

Primary Outcome Measures

Name	Time	Method
Initial biological profile of children with COVID-19 infection	Day 0	Describe the immune response (biological profile in blood samples) of children and adults with COVID-19 infection and correlate it with the initial clinical presentation; measurement of the following parameters in blood at time of inclusion: white blood cell count, C-reactive protein, procalcitonin, hepatic and renal functions, ferritin, vitamin C and D, fibrinogen, prothrombin time test and partial thromboplastin time in order to correlate them with the initial clinical presentation.
Initial immunological profile of children with COVID-19 infection	Day 0	measurement of the following parameters in blood at time of inclusion: interferon alpha and gamma, Tumor necrosis factor (TNF) alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte Human Leukocyte Antigen - DR isotype (HLA-DR) expression in order to correlate them with the initial clinical presentation.

Secondary Outcome Measures

Name	Time	Method
Evolution of the immunological profile of children with COVID-19	Within 21 days following inclusion	measurement of the following parameters in blood at day 7, and at time of worsening: interferon alpha and gamma, TNF alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte HLA-DR expression in order to correlate them with with the secondary worsening
titers in specific Immunoglobulin G (IgG) antibodies of children with COVID-19	Within 21 days following inclusion	Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening
Clinical worsening	Within 21 days following inclusion	Determine whether the initial biological and immunological profiles (see primary outcome measures) are predictive of a secondary worsening (i.e., admission to intensive care unit, and/or increase in NEWS-2 score, and/or increase in oxygen dependence level) of COVID-19 infection
Nasopharyngeal swabs SARS-CoV-2 viral loads of children with COVID-19	Within 21 days following inclusion	Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured within 21 days following inclusion, and correlation to the secondary worsening
titers in specific Immunoglobulin M (IgM) antibodies of children with COVID-19	Day 0	Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured at day 0 and correlation to the initial clinical presentation
titers in specific Immunoglobulin G (IgM) antibodies of children with COVID-19	Within 21 days following inclusion	Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening

Trial Locations

Locations (12)

Groupement Hospitalier Nord-Daupine; 🇫🇷 Bourgoin-Jallieu, France

Hôpital Louis Pradel; 🇫🇷 Bron, France

Hôpital Louis Mourier; 🇫🇷 Colombes, France

Hopital de la Croix-Rousse; 🇫🇷 Lyon, France

Centre Hospitalo-Universitaire de Grenoble; 🇫🇷 La Tronche, France

Hôpital Edouard Herriot; 🇫🇷 Lyon, France

Hôpital mère - enfant Nantes; 🇫🇷 Nantes, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Hôpital Nord de Saint Etienne; 🇫🇷 Saint-Priest-en-Jarez, France

Hôpital Nord-Ouest; 🇫🇷 Villefranche-sur-Saône, France

Centre Hospitalier D'Annecy-Genevois; 🇫🇷 Épagny, France

Hôpital femme-mère-enfant; 🇫🇷 Bron, France