(2020- 2.1.1-ED-2022-00198) Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs
Hivatal
(KP2021-EGA-29)
(OTKA K131479) Támogató: OTKA
(2020-1.1.6-JOVO-2021-00013)
(RRF-2.3.1-21-2022-00003)
(TKP2021-EGA-23) Támogató: Innovációs és Technológiai Minisztérium
Szakterületek:
Akut légzőszervi tünetegyüttes (SARS)
Klinikai orvostan
Vakcinák
BackgroundTo investigate the factors that have significant impact on the Severe
Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced
immune response in rheumatoid arthritis (RA).MethodsSerological response
was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated
response was measured by a whole-blood test quantifying the interferon (IFN)-γ response
to different SARS-CoV-2-specific domains.ResultsWe prospectively enrolled
109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed
infection or the last vaccination dose and the day when samples were taken (“sampling
interval”) was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific
antibodies were detected in 94% of RA patients. Among the investigated patient related
variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001)
and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant
effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased
the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor
and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared
to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased
the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001).
The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic
citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S
levels, than the anti-CCP negative patients. Positive T-cell response was observed
in 87% of the healthy volunteer group and in 52% of the RA patient group. Following
vaccination or infection it declined significantly (p= 0.044) but more slowly than
that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased
by 65% in patients treated with anti-CD20 therapy (p=0.055).ConclusionOur
study showed that the SARS-CoV-2-specific antibody levels were substantially reduced
in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In
addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular
immune responses. Furthermore, the magnitude of humoral and cellular immune response
was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine
effectively increased the level of anti-S antibodies.
