Discussion
The occurrence of post-infective and para- infectious arthritis
following viral infection is not uncommon, but with the current
pandemic, the incidence has increased (6). The spectrum of
musculoskeletal complaints associated with viral infection can range
from mild arthralgia to chronic arthritis (13).
Joint involvement in SARS-CoV-2 infection may occur at any time during
the course of infection (14). It may be an initial symptom of the
infection, emerge during the acute phase (sometimes during
hospitalization), or occur after recovery (14). Coronaviruses generally
appear to cause arthralgias and myalgias rather than true inflammatory
arthritis (15). Arthralgias are reported in 15% of COVID-19 patients,
and myalgias in 44% of patients (13). PCA, which was previously
reported in October 2020 during the first wave of the COVID pandemic,
has been well established as a clinical entity requiring medical
attention (16). Several clinical forms of PCA have been described
(17-19). It may present with mono- or oligoarticular involvement,
however clinical and epidemiological data of PCA indicate that
monoarthritis was the most common form of involvement, with prominent
involvement of the lower extremity joints (17). The most frequently
affected joints are the knee, ankle, and proximal interphalangeal joint
(17) and such was the case in our patients, whose knee joint was
affected. PCA is often diagnosed in young adults between the ages of 18
and 40 years (20), such was the case with our 33 year old female
patient. The incidence of PCA is high in the male population (17). The
lag time between SARSCoV2 infection and arthritis onset varied between
cases, usually, starting some days or a few weeks after the resolution
of other infection manifestations and usually during the healing period
(median: 18 days) (21) similar to that noted in both our patients, whose
arhritis onset delay was respectively of 20 and 15 days. The
predisposing factors for developping joint involvement following
SARS-CoV-2 infection are still unknown, but in reviewing the
litterature, it appears that the virus’ prolonged persistence, as
evidenced by prolonged positivity of nasopharyngeal swabs for
SARS-CoV-2, and its spread from the respiratory tract to other sites,
including the gastrointestinal tract, could locally activate
immunological and inflammatory pathways and lead to the development of
arthritis in some patients (22),
Although different mechanisms have been suggested in the
etiopathogenesis of virus-induced arthritis, the exact mechanisms by
which COVID-19 could cause joint inflammation are only partially
understood (23). For a long time, it was assumed that SARS-CoV-2
infection resulted in macrophage stimulation, which in turn caused the
release of high levels of cytokines and chemokines that enhanced the
inflammatory process (23). Previous and current studies demonstrate that
coronaviruses share molecular epitopes with human proteins (e.g., spike
glycoprotein S) that play a key role in host cell invasion and evade
immune response attacks, conferring immune invasive capacity to the
infectious agent (24). This molecular mimicry appears to be most
prominent (25), by triggering humoral and cellular self-reactivity in
the host at the end of the process by which the epitope interacts
between a viral agent and the host (26), and it is well known to be
responsible for eliciting autoimmune responses in susceptible
individuals (27). And this mechanism may be involved in the pathogenesis
of acute systemic infection and virus-related post-infection
immunological consequences (28). Mimetic epitopes may also be present in
the synovial membrane and cause acute local inflammation through similar
pathways (28). Other suggestive examples of diseases induced by
molecular mimicry after COVID-19 come from recent publications reporting
cases of Guillain-Barre and Miller Fisher syndrome (29, 30).
Other theories suggest that circulating immune complexes or a possible
localization of the virus directly on the joint tissues are involved
(31). However, RT-PCR for the detection of SARS-CoV2 nucleic acids did
not show that the virus was present in synovial fluid, validating the
hypothesis of an immune-mediated process.
Given the worldwide frequency of COVID-19 and the large affected
population, the number of reported PCA is small (32). A credible
justification for the lower incidence of musculoskeletal inflammation is
COVID-19 treatment with corticosteroids, which likely attenuated the
musculoskeletal manifestations (32). Although hydroxychloroquine is
inefective for treating COVID-19, it has been shown to be effective in
the management of systemic rheumatological diseases, especially with
inflammatory joint involvement (33). Most reported PCA cases show a
prompt and complete response to nonsteroidal anti-inflammatory drugs,
and this was also the case in our patients. Treatment duration can be
extended for 2-4 weeks, as with other viral arthritis. However, steroid
treatment is occasionally needed, and is preferred by intra-articular
injection (in case of mono-oligoarticular involvement). In a few cases,
systemic steroid is necessary, but generally for short periods (34).
Only a few cases of PCA have required immunosuppressive drugs
(methotrexate and sulfasalazine) (35). Some patients with joint
manifestations and severe lung involvement, as part of a
hyperinflammatory syndrome, have been treated with IL-6 inhibitors or
Jak inhibitors, with significant improvement in both lung and joint
manifestations (36).
In conclusion, As the number of patients recovering from COVID-19
increases, more and more data on post-infectious complications will
emerge. Various autoimmune and rheumatic diseases have been reported in
COVID-19 survivors. COVID-19 can also cause flare-ups of pre-existing
rheumatic diseases. Both of our cases are consistent with what has
already been reported in the literature confirming the development of
PCA and strengthen the impending necessity of wider studies to identify
rheumatologic manifestations in the short- and long-terms after
surviving COVID-19. Follow-up in the coming months will help to
determine the chronicity of these inflammatory conditions. A better
understanding of the immune consequences that accompany SARS-CoV-2
infection is required both to determine the immunopathogenic mechanisms
capable of promoting or contrasting the development of rheumatic
manifestations, and to adequately deal with such a complication.