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CLINICAL AND IMMUNOLOGICAL RELATIONSHIP
BETWEEN COVID-19 AND RHEUMATOID ARTHRITIS
Nargiza Khakimzhanovna Abduazizova
Zafar Abdunaemovich Sharapov
TASHKENT MEDICAL ACADEMY, TASHKENT, UZBEKISTAN
Abstract:
Rheumatoid arthritis is the most common inflammatory disease of the
joints, characterized by erosive symmetrical polyarthritis in combination with systemic
immune-inflammatory damage to internal organs. One of the most severe and
widespread inflammatory diseases of the joints. Rheumatoid arthritis is a common
disease, occurring in all countries in approximately 1% of the total population. New
data have shown that respiratory viral infections may increase the risk of autoimmune
inflammatory arthritis, such as rheumatoid arthritis. In addition, infections may worsen
the disease in patients with inflammatory arthritis.
Key words:
COVID-19, immune-inflammatory rheumatic diseases, diagnostics,
cytokines.
Relevance:
The incidence of the new coronavirus COVID-19 is considered by
the world community as an emergency of international concern. Along with its
enormous social significance, the COVID-19 pandemic has highlighted a number of
fundamentally new clinical and fundamental problems in the immunopathology of
human diseases. This problem is extremely relevant for patients suffering from
immune-mediated inflammatory rheumatic diseases, due to their higher susceptibility
to infectious complications [1]. The coronavirus disease 2019 (COVID-19) pandemic,
etiologically associated with the SARS-CoV-2 (severe acute respiratory syndrome
coronavirus-2) virus, has drawn attention to new clinical and fundamental problems in
the immunopathology of human diseases associated with virus-induced autoimmunity
and autoinflammation [2]. Currently, the infection caused by the new coronavirus –
COVID-19, is considered by the world community as a global emergency.
Rheumatologists are particularly concerned about this problem, since patients with
immune-inflammatory rheumatic diseases (IIRD) have an increased risk of developing
infectious diseases and are treated with drugs that have an immunosuppressive effect
[3,8,9]. The early period of rheumatoid arthritis plays a decisive role in the
development and progression of immune complex inflammation. At the same time,
early diagnosis of RA allows for adequate treatment and a more significant clinical
effect, as well as improving the prognosis of this disease [5,10,12]. Early diagnosis,
regular monitoring of disease activity, and a treat-to-target strategy are recommended
for both CPA-positive and -negative RA, but the efficacy of individual drugs in these
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subtypes may vary significantly. The development of autoimmune and rheumatic
diseases in patients who have had COVID-19 is a pressing public health issue. COVID-
19 may unmask previously undiagnosed rheumatic conditions or trigger the disease
denovo [6,10]. As noted earlier, patients with IVR3 have a higher risk of developing
infections than the general population, which reflects the immunopathological
disorders inherent in these diseases. In addition, the risk of infection is clearly
associated with the degree of activity of the process [7,10,11].
Materials and methods of the study:
The study included 120 patients with
rheumatoid arthritis (meeting the criteria of EULAR/ACR, 2010). During the study,
patients were divided into 2 groups: the main group - 60 patients with rheumatoid
arthritis who had COVID-19, and the control group - 60 patients with rheumatoid
arthritis who had not had COVID-19. Patients were studied in comparison based on the
analysis of clinical, laboratory and instrumental parameters.
Results of the study:
At the time of the study, the average age of patients was
41.7±11.7 years, the average duration of the disease was 10.7±5.8 years. According to
the anamnesis, 75 (62.5%) patients with RA had a gradual onset of the disease, and 35
(29%) had an acute onset. The course of the disease in the main group (RA patients
who had COVID-19) differed in a number of aspects. According to current scientific
data, viral infections can increase the severity of inflammation or aggravate an existing
immune imbalance in autoimmune diseases, including RA. According to our
observations: morning sickness was observed in 89% of patients in group I and in 82%
of patients in the control group. The duration of morning stiffness averaged 89±19.3
minutes in group I and 70±14.8 minutes in group II. Thus, it was found that both the
percentage of morning stiffness and its duration were higher in RA patients who had
COVID-19. Participants in Group I experienced frequent fatigue, general malaise, and
even sleep disturbances or constant weakness, which are symptoms of “post-Covid
syndrome”. In Group II, these symptoms were observed comparatively less frequently.
Patients who recovered from COVID-19 showed elevated levels of almost all
indicators. This is explained by the fact that in RA, the existing autoimmune process is
further aggravated by a viral infection, triggering a cascade of inflammatory reactions.
Thus, previously unobserved or rare complications may also be more pronounced in
RA patients who have had COVID-19 in clinical practice (Table 1).
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Table 1
Clinical signs
Group I
(abs)
Group I (%)
Group II
(abs)
Group II (%)
Increased subfebrile
temperature
26
43.3
15
25.0
Myalgia
34
56.7
23
38.3
Lymphadenopathy
12
20.0
9
15.0
Rheumatoid nodule
9
15.0
7
11.7
Defiguration
24
40.0
21
35.0
Deformation
24
40.0
20
33.3
Ankylosis
6
10.0
5
8.3
Contracture
11
18.3
9
15.0
Cutaneous vasculitis
5
8.3
3
5.0
Keratoconjunctivitis
(Sjögren's syndrome)
4
6.7
2
3.3
Pleurisy / pericarditis
6
10.0
3
5.0
Interstitial lung injury
10
16.7
6
10.0
Systemic vasculitis
5
8.3
4
6.7
Note: "Abs" is the absolute number (how many out of 60 people it occurred in).
"%" shows how many out of 60 it occurred in as a percentage.
Laboratory and instrumental data of patients with RA who had COVID-19:
It is known that the assessment of disease activity in patients with RA is important for
further treatment of the patient and prognosis of the disease course. In the study groups,
the level of C-reactive protein was 1.5 times higher in the main group than in the control
group, and 11.3 times higher than in healthy people (p<0.05). The level of C-reactive
protein in the control group was 5.9 times higher than in the control group (p<0.05).
Thus, coronavirus infection affects the activity of the disease in patients with RA, and
the severity of the inflammatory process aggravates the course of the disease. In Group
II, the duration of RA was up to 6 months, it was detected in 40.3% of patients (p<0.05).
Isolated erosions were detected in another 9% of patients in this group (p<0.05). Most
patients in group III (60.6%) showed signs of osteoporosis, small cystic foci of luminal
changes at the site of the disease, and 18.8% of patients had single erosions (p<0.05).
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The main group had the highest frequency of stage III sacroiliitis (35%, i.e. 21
patients). The control group had a higher incidence of stage II sacroiliitis (52.5%, i.e.
21 patients). Stage I sacroiliitis was also quite common in the control group (25%, 10
patients). Stage III sacroiliitis (with joint erosions and bone narrowing) was 2.5 times
more common in patients with COVID-19. Thus, severe cases of sacroiliitis are more
common in patients who have had COVID-19. This condition may be associated with
a long course of the disease and high inflammatory activity.
Dynamics of proinflammatory cytokines in selected groups: in local inflammation
foci in RA patients, immune cells and proinflammatory cytokines, including IL-6, IL-
17 and TGF β1, play a decisive role in the pathogenesis of autoimmune inflammation.
Activation of cytokines and immunity in patients with COVID-19 is similar to that in
patients with RA. Based on these data, we examined the cytokines IL-6, IL-17 and
TGF β1. When studying the concentration of TGF β1 in blood plasma, it was 26±0.6
ng/ml and 21±0.6 ng/ml in the main and control groups, respectively, and in healthy
individuals – 15±0.6 ng/ml. The IL-6 level increased by 1.5 times compared to the
control group and averaged 32.31±1.6 pg/ml (p<0.05). It is known that IL-6 directly
induces the synthesis of acute phase proteins in hepatocytes and stimulates the
production of antibodies by B cells, controlling the differentiation of plasma cells.
Based on the findings of scientific studies, IL-17. It was found that its level in the blood
serum of patients with early RA was three times higher than that of patients in the
control group (19.30±2.79 pg/ml and 6.23±2.98 pg/ml, respectively; r<0.05). Elevated
cytokine levels indicate more active inflammation in patients with COVID-19 (Table
2).
Table 2
Serum cytokine frequencies in RA patients and control subjects
with COVID-19
Cytokines
pg/ml
Control group
(n=20)
Patients with RA
who have had
covid
(n=55)
Reliability of
differences
(p)
IL-6
13,89±4,56
32,31 ±1,6*
p<0,05
IL-17
6,23± 2,98
19,30±2,79*
p<0,05
TGF β1
7,72±3,98
26±0.6 ±9,96*
p<0,05
Note: * p<0.05. Significant difference from healthy people
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When monitoring the amount of cytokines in dynamics, it took the following form
according to the table:
Dynamics of cytokine indicators in patients
Main group
Control group
Indicator
1-month
3 month
6-month
1-month
3 month
6-month
Interleukin
6 (1,3 - 6,8
пг/мл)
32,31
±1,6*
24,31
±1,3*
13,31
±2,6*
23,89±4,5
6
13,89±4,5
6
7,9±4,56
Interleukin
17 (87-104
пг/мл)
159,30±2,
79*
142,30±3,
79*
135,30±2,
79*
148,23±
2,98
110,23±
2,98
98,23±
2,98
When comparing the results of immunoinflammatory markers, a directly
proportional increase in IL-6 and IL-17A was noted compared to C-reactive protein.
Expression of radiographic features in groups
Radiological sign
Patients with RA
who had COVID-
19 (%)
RA patients who
did not have
COVID-19 (%)
Periarticular osteopenia (decreased
bone density)
77
60
Accumulation of fluid in the joint
cavity
67
54
Changes in the composition of the joint
space (narrowing of the joint space)
57
50
Erosion
62
55
Subluxation/dislocation (dislocation of
joints)
37
30
Deformation of joints
46
39
Cystic changes
33
25
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Patients with RA who had COVID-19 had higher rates of many radiographic
features (periarticular osteopenia, joint effusion, erosions, subluxation/dislocation,
joint deformity, and cystic changes) compared with patients who did not have COVID-
19. This is explained by the fact that COVID-19 infection negatively affects the course
of RA, causing additional inflammation and tissue damage.
Conclusions:
The pandemic and COVID-19 are not only an emergency in global
health care, but also a major factor in global problems. This problem is especially
relevant for patients with IVRZ. Thus, the revealed data may testify in favor of an
important diagnostic role of RA. Evaluation of laboratory and instrumental parameters
can be used as prognostic criteria for rheumatoid arthritis.
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