Clinical trial NCT04750720: Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection
Official title: Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection According to the Clinical Severity of the Infection.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
SARS-CoV-2
Keywords: Covid19
SARS-CoV-2
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
Collaborators: name: Institut Pasteur
First posted: 2021-02-11
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Collection of biological samples (M0, M3, M6, M9, M12, M15, M18, M24) with associated data for the study of the kinetics of antibodies anti COVID-19 in subjects with documented SARS-CoV-2 infection (PCR and/or positive specific serology)
Primary purpose: BASIC_SCIENCE

Brief summary: The main objective of the study is to describe the temporal curve of COVID-19 IgG and neutralizing antibodies over 24 months in an identified population of patients who presented with SARS-CoV-2 virus infection. The secondary objectives are to characterize the kinetics of the antibodies according to the severity of the clinical presentation and patient's characteristics and to determine if the anti-SARS-CoV-2 antibodies retain their neutralizing capacity over time. A sub-study aims to describe the kinetic of neutralizing antibodies (in blood and nasal mucosa) after vaccination.

Detailed description: Given the seriousness of the global health consequences of the COVID-19 pandemic and the difficulty of covering the world population with effective vaccination, several questions arise:

* Are the antibodies made by a patient neutralizing and do they protect the individual from further contamination?
* What is the persistence of the antibodies over time according to the clinical presentation, knowing that the very symptomatic forms have developed a much higher level of antibodies than the forms followed only on an outpatient basis and no less severe?
* What is the impact of vaccination (against wild-type virus and emerging variants) ? The investigators propose a single-center, observational study including 300 patients to answer the two questions, by selecting from the file of all the patients having had a positive RT-PCR 3 distinct groups: severe (hospitalized), pauci-symptomatic to moderate (followed in ambulatory only). Note: people living with HIV can be included in each of the groups.

MAIN EVALUATION

\> Presence of specific anti-SARS-CoV-2 antibodies in the different study groups at M24 at each of the sampling times (M0, M3, M6, M9, M12, M15, M18, M24)

SECONDARY EVALUATION CRITERIA

* Presence of specific anti-SARS-CoV-2 antibodies in the different groups of the study at M12 and in each of the subgroups at M12 and M24
* Neutralizing capacity of anti-SARS-CoV-2 antibodies to M6, M12 and M24 on the classical strain and the new variants, before and after a possible vaccination against COVID-19
* Measurement of CD8 (CD38 + DR +), CD4 and activated B lymphocytes in culture This will make it possible to answer the question of the persistence or not of an immune response over 24 months, an essential element in the event of seasonal circulation of the virus in the years to come, and of the persistence or not of the neutralizing capacities of these antibodies in the over time, especially when the title approaches the detection threshold.

These information will be decisive in the event of successive waves of the SARS-CoV-2 epidemic given a low level of collective immunity (\<10% in France at the end of 2020) in order to know whether previously affected patients are durably protected.

In the context of a lack of vaccine, results from this study would make it possible to select candidates for vaccination from the truly non-immune population.

Vaccine sub-study :

Study of the kinetic of neutralizing antibodies after vaccination :

Volunteers participants, provided they give a special agreement for the vaccine sub-study, will undergo an additional grid of samples to accurately study the kinetic of neutralizing antibodies before and monthly after (up to 6 months) receiving anti-SARS-CoV-2 vaccine (whatever the product used). A special attention will be given to the capacity of their antibodies to neutralize emerging variants. Samples will include blood and possibly nasopharyngeal swabs (not mandatory).

Eligibility criteria: Inclusion Criteria:

* Age \> 18
* Having had a confirmed infection with CoV-2-SARS by RT-PCR and/or serology (IgM and/or IgG specific as significant)
* Being vaccinated against anti-SARS-CoV-2 (vaccine sub-study)
* Benefiting from a Social Security system
* Having consented to participate in the study
* Accepting regular follow-up for 24 months

Exclusion Criteria:

* Protected person (under guardianship or trusteeship)
* Person under the protection of justice
* Person unable to express consent

Primary outcomes:
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 0
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 3
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 6
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 9
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 12
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 15
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 18
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 24
Secondary outcomes:
measure: Presence of specific anti-SARS-CoV-2 antibodies
timeFrame: Month 12
measure: Presence of specific anti-SARS-CoV-2 antibodies in subgroups
timeFrame: Month 12
measure: Presence of specific anti-SARS-CoV-2 antibodies in subgroups
timeFrame: Month 24
measure: Neutralizing capacity of anti-SARS-CoV-2 antibodies
timeFrame: Month 6
measure: Neutralizing capacity of anti-SARS-CoV-2 antibodies
timeFrame: Month 12
measure: Neutralizing capacity of anti-SARS-CoV-2 antibodies
timeFrame: Month 24
measure: Measurement of activated CD8 (CD38+DR+) in culture
timeFrame: Month 6
measure: Measurement of activated CD8 (CD38+DR+) in culture
timeFrame: Month 12
measure: Measurement of activated CD8 (CD38+DR+) in culture
timeFrame: Month 24
measure: Measurement of activated CD4 in culture
timeFrame: Month 6
measure: Measurement of activated CD4 in culture
timeFrame: Month 12
measure: Measurement of activated CD4 in culture
timeFrame: Month 24
measure: Measurement of activated B lymphocytes in culture
timeFrame: Month 6
measure: Measurement of activated B lymphocytes in culture
timeFrame: Month 12
measure: Measurement of activated B lymphocytes in culture
timeFrame: Month 24
Other outcomes:
Locations:
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans, France
Study officials:
affiliation: CHR ORLEANS
name: Thierry PRAZUCK, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Garcia L, Woudenberg T, Rosado J, Dyer AH, Donnadieu F, Planas D, Bruel T, Schwartz O, Prazuck T, Velay A, Fafi-Kremer S, Batten I, Reddy C, Connolly E, McElheron M, Kennelly SP, Bourke NM, White MT, Pelleau S. Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination. Viruses. 2022 Jul 8;14(7):1491. doi: 10.3390/v14071491.