Host-pathogen Interactions During SARS-CoV-2 Infection

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Trial

— HPI-COVID-19  

Official title:

Host-pathogen Interactions During Paediatric and Adult SARS-CoV-2 Infection (COVID-19)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04376476
• Other study ID #: 69HCL20_0342
• Secondary ID: 2020-A01102-37
• Status: Completed
• Phase: N/A
• Start date: May 5, 2020
• Est. completion date: May 13, 2022

Study information

• Verified date: April 2023
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: May 13, 2022
• Est. primary completion date: May 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

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 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.

Related Conditions & MeSH terms

• Communicable Diseases
• Coronavirus Infections
• COVID-19
• Infection, Coronavirus
• Infections
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2

Intervention

Biological:
• Blood sample
blood samples will be taken as below: Group E1: At day 0 Group E2: At day 0, day 7, day 14 Group E3: At day 0
• Low or upper respiratory tract sample
Low or upper respiratory tract sample will be collected in order to take virology measurements: Group E1: At day 0 Group E2: At day 0, day 7, day 14 Group E3: At day 0
• Stool collection or fecal swab
The stool collection or fecal swab will be collected in order to take virology measurements: Group E1: / Group E2: At day 0, day 7, day 14 Group E3: At day 0

Other:
• phone call
phone calls will be performed to collect data regarding patients' symptoms at: Group E1: Day 14 Group E3: Day 14

Locations

Country	Name	City	State
France	Groupement Hospitalier Nord-Daupine	Bourgoin-Jallieu
France	Hôpital femme-mère-enfant	Bron
France	Hôpital Louis Pradel	Bron
France	Hôpital Louis Mourier	Colombes
France	Centre Hospitalier D'Annecy-Genevois	Épagny
France	Centre Hospitalo-Universitaire de Grenoble	La Tronche
France	Hopital de la Croix-Rousse	Lyon
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

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initial biological profile of children with COVID-19 infection	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.	Day 0
Primary	Initial immunological profile of children with COVID-19 infection	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.	Day 0
Secondary	Clinical worsening	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	Within 21 days following inclusion
Secondary	Evolution of the immunological profile of children with COVID-19	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	Within 21 days following inclusion
Secondary	Nasopharyngeal swabs SARS-CoV-2 viral loads of children with COVID-19	Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured at day 0 and correlation to the initial clinical presentation	Day 0
Secondary	titers in specific Immunoglobulin G (IgG) antibodies of children with COVID-19	Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured at day 0 and correlation to the initial clinical presentation	Day 0
Secondary	titers in specific Immunoglobulin M (IgM) antibodies of children with COVID-19	Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured at day 0 and correlation to the initial clinical presentation	Day 0
Secondary	Nasopharyngeal swabs SARS-CoV-2 viral loads of children with COVID-19	Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured within 21 days following inclusion, and correlation to the secondary worsening	Within 21 days following inclusion
Secondary	titers in specific Immunoglobulin G (IgG) antibodies of children with COVID-19	Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening	Within 21 days following inclusion
Secondary	titers in specific Immunoglobulin G (IgM) antibodies of children with COVID-19	Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening	Within 21 days following inclusion