Host-pathogen Interactions During SARS-CoV-2 Infection

NCT04376476 | Completed

• 2 other identifiers: 69HCL20_03422020-A01102-37
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 12

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.

Conditions

Infection, Coronavirus; Severe Acute Respiratory Syndrome Coronavirus 2

Keywords

Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19; immunology; interferon; coronavirus

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• Clinical worsening

  Within 21 days following inclusion

• Evolution of the immunological profile of children with COVID-19

  Within 21 days following inclusion

• Nasopharyngeal swabs SARS-CoV-2 viral loads of children with COVID-19

  Day 0

• titers in specific Immunoglobulin G (IgG) antibodies of children with COVID-19

  Day 0

• titers in specific Immunoglobulin M (IgM) antibodies of children with COVID-19

  Day 0

Study Arms (3)

Children group E1

EXPERIMENTAL

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.

Biological: Blood sample; Biological: Low or upper respiratory tract sample; Other: phone call

Children group E2

EXPERIMENTAL

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).

Biological: Blood sample; Biological: Low or upper respiratory tract sample; Biological: Stool collection or fecal swab

Children group E3

EXPERIMENTAL

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.

Biological: Blood sample; Biological: Low or upper respiratory tract sample; Biological: Stool collection or fecal swab; Other: phone call

Interventions

Blood sample BIOLOGICAL

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

Children group E1; Children group E2; Children group E3

Low or upper respiratory tract sample BIOLOGICAL

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

Children group E1; Children group E2; Children group E3

Stool collection or fecal swab BIOLOGICAL

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

Children group E2; Children group E3

phone call OTHER

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

Children group E1; Children group E3

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (12)

Groupement Hospitalier Nord-Daupine

Bourgoin, 38300, France

Location

Hôpital femme-mère-enfant

Bron, 69677, France

Location

Hôpital Louis Pradel

Bron, 69677, France

Location

Hôpital Louis Mourier

Colombes, 92700, France

Location

Centre Hospitalier D'Annecy-Genevois

Épagny, 74370, France

Location

Centre Hospitalo-Universitaire de Grenoble

La Tronche, 38700, France

Location

Hopital de la Croix-Rousse

Lyon, 69317, France

Location

Hôpital Edouard Herriot

Lyon, 69437, France

Location

Hôpital mère - enfant Nantes

Nantes, 44093, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hôpital Nord de Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Hôpital Nord-Ouest

Villefranche-sur-Saône, 69655, France

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 6, 2020
• Study Start: May 5, 2020
• Primary Completion: May 13, 2022
• Study Completion: May 13, 2022
• Last Updated: April 5, 2023

Record last verified: 2023-04

Locations

FR (12)