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.
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.
Biological: blood tests
Memory T and B cell response assessment Humoral response assessment (Specific anti-Sars-Cov-2 antibodies characterization)
Other Name: Immune response assessment
Biological: Nasopharyngeal swabs
SarS-Cov-2 viral load assessment
Biological: Stools
SarS-Cov-2 viral load assessment
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
Cochin hospital
Paris, France
Corinne Miceli-Richard, MD, PhD, Principal Investigator
Assistance Publique - Hôpitaux de Paris