SarS-Cov-2 Viral Infection (COVID-19) in Patients With Chronic Inflammatory Rheumatism (COVIRIC)

Study of the Viral Load and Humoral and Cellular B and T Responses in Patients With Rheumatoid Arthritis and Spondyloarthritis Under Immunosuppressive Treatments

The purpose of this study is to assess whether immunosuppressive therapies used by patients with chronic inflammatory rheumatic diseases have an impact on the viral load and the humoral and cellular responses during viral infection with SarSCoV2, compared to members of their family cluster infected with the same viral strain.

Study Overview

• Status: Terminated
• Conditions: Covid19; Rheumatoid Arthritis; Spondyloarthritis
• Intervention / Treatment: Biological: blood tests; Biological: Nasopharyngeal swabs; Biological: Stools

Detailed Description

Rheumatoid arthritis (RA) and spondyloarthritis (SPA) are the two most common chronic inflammatory rheumatic diseases, with a prevalence of 0.5-1% for RA and about 0.35% for SPA. Many studies have described an increased risk of serious infectious diseases directly associated with increased morbidity and mortality among those patients. This increased risk (frequency and severity) results from the disease itself, especially if the rheumatism is not controlled with high disease activity, but also due to the immunosuppressive treatments used to treat these patients. The risk of infection is measured by the Incidence Rate (IR) corresponding to the number of events (infections) per 100 patients/years of follow-up. This risk is accepted as comparable between patients with SpA or RA and ranges from 22 to 34/100 patient-years, depending on the studies, for patients on biologics. The risk of infection is higher for patients on biotherapy than for patients on Disease Modifying Anti-Rheumatic Drugs (DMARDs - mainly Methotrexate) and the combination of corticosteroid therapy with the biotherapies further increases this risk of infection. Lung and upper respiratory tract infections are the most common infections observed under biotherapy. The risk of infection may be different depending on the biotherapy considered. Moreover, the vaccine response is also highly variable depending on the biotherapy, treatments with Rituximab, methotrexate and abatacept being those interfering the most with the quality of the vaccine response. The working hypothesis is therefore that certain immunosuppressive treatments used in these inflammatory rheumatic conditions may interfere with the humoral and/or cellular anti-SarS-Cov-2 immune response.

Since December 2019, the first SARS-Cov-2 (Severe acute respiratory coronavirus 2 syndrome) infections have been described in Wuhan province in China. In April 2020, 1,824,950 people were officially infected in 193 countries worldwide with 112,510 deaths reported (Agence France Presse and World Health Organization; 13 April 2020). To date, the investigators have a limited amount of data concerning the seroconversion of infected subjects, the protective or non-protective nature of the specific antibodies generated, and the duration of protection. No data have been generated on the specific B and T responses of SarS-Cov-2. In addition, the few available data in the literature on SarS-Cov-2 only concern the general population, not exposed to immunosuppressive treatments.

However, major questions are currently unanswered for patients on immunosuppressive treatments: Are they excreting the virus for longer periods of time? How long can this viral excretion be measured in the upper airways and in the stool? Do they develop a humoral and cellular immune response similar to the general population? Accurate knowledge of the dynamics of the virus and the immune response induced will be essential for the development of strategies for antiviral treatment, vaccination protocols and for the epidemiological control of Covid-19.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Cochin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

cases

• Patient with spondyloarthritis fulfilling the ASAS criteria
• Patients with rheumatoid arthritis fulfilling the ACR/EULAR criteria and
• Immunosuppressive therapy: Methotrexate, leflunomide, anti-TNF, Anti-IL6R, abatacept, rituximab, Jak inhibitors (tofacitinib or baricitinib) And
• infected with the SarS-Cov-2 (positive PCR and/or serology and/or CT-scan)

Controls:

• Family cluster member confined to the same location as the index subject
• Infected with the SarS-Cov-2 (positive PCR and/or serology and/or CT-scan)

Exclusion Criteria:

cases and controls

• Pregnant woman
• Breastfeeding woman
• Immunosuppressed subject for members of the familiar cluster of the index subject
• Patient with no social security
• Patients whose freedom is limited by the judicial or administrative authority
• Patients under legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: case; Index cases (RA and SpA patients under immunosuppressive treatments)	Biological: blood tests; Memory T and B cell response assessment Humoral response assessment (Specific anti-Sars-Cov-2 antibodies characterization); Other Names: Immune response assessment; Biological: Nasopharyngeal swabs; SarS-Cov-2 viral load assessment; Biological: Stools; SarS-Cov-2 viral load assessment
OTHER: controls; Members of index cases family cluster infected with the same viral strain	Biological: blood tests; Memory T and B cell response assessment Humoral response assessment (Specific anti-Sars-Cov-2 antibodies characterization); Other Names: Immune response assessment; Biological: Nasopharyngeal swabs; SarS-Cov-2 viral load assessment; Biological: Stools; SarS-Cov-2 viral load assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of SarS-Cov-2 RNA in feces and nasopharyngeal swabs	Nasopharyngeal swabs : Detection of SarS-Cov-2 RNA	up to Day 30
Detection of SarS-Cov-2 RNA in feces and nasopharyngeal swabs	Nasopharyngeal swabs : Detection of SarS-Cov-2 RNA	between Day 30 and Day 90
Detection and quantification of IgG, IgM and IgA specific for SarS-Cov-2 N and S proteins in blood		up to Day 30
Detection and quantification of IgG, IgM and IgA specific for SarS-Cov-2 N and S proteins in blood		between Day 30 and Day 90
Detection and quantification of IgG, IgM and IgA specific for SarS-Cov-2 N and S proteins in blood		6 Months
Detection and quantification of IgG, IgM and IgA specific for SarS-Cov-2 N and S proteins in blood		12 Months
Detection and quantification of IgG, IgM and IgA specific for SarS-Cov-2 N and S proteins in blood		24 Months
Isolation and characterization of B and T lymphocytes in blood		up to Day 30
Isolation and characterization of B and T lymphocytes in blood		between Day 30 and Day 90
Isolation and characterization of B and T lymphocytes in blood		6 Months
Isolation and characterization of B and T lymphocytes in blood		12 Months
Isolation and characterization of B and T lymphocytes in blood		24 Months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Corinne Miceli-Richard, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2020
• Primary Completion (ACTUAL): February 21, 2022
• Study Completion (ACTUAL): February 21, 2022

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: October 12, 2020
• First Posted (ACTUAL): October 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: COVID19; Sars-Cov-2; Rheumatoid arthritis; Spondyloarthritis; Immunosuppressive treatments
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; COVID-19; Arthritis; Arthritis, Rheumatoid; Spondylitis; Spondylarthritis
• Other Study ID Numbers: APHP200598

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No