e-ISSN 1941-5923

© Am J Case Rep, 2023; 24: e939870

DOI: 10.12659/AJCR.939870

Received: 2023.02.14
Accepted: 2023.05.11 Inflammatory Arthritis After COVID-19:
Available online:  2023.05.31
Published: 2023.06.27 A Case Series
Authors’ Contribution: ABCDEF 1 Siddhant Yadav 1 Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA
Study
Design  A DEF 1 Sara L. Bonnes 2 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
Data Collection  B 3 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic,
Analysis  C
Statistical DEF 1 Elizabeth A. Gilman Rochester, MN, USA

Data Interpretation  D DE 1 Michael R. Mueller 
Manuscript Preparation 
E E 1 Nerissa M. Collins
Literature Search  F

Funds Collection  G ABCDEF 1-3 Ryan T. Hurt
ABCDEF 1 Ravindra Ganesh 

Corresponding Author: Siddhant Yadav, e-mail: Yadav.siddhant@mayo.edu

Financial support: The study was funded by the GHR Foundation
Conflict of interest: RTH is a consultant for Nestle Nutrition; RG is a consultant for Alpaca Health

Case series
Patients: Female, 45-year-old • Female, 46-year-old • Female, 54-year-old • Female, 61-year-old •
Female, 19-year-old
Final Diagnosis: Arthritis • rheumatoid arthritis
Symptoms: Fatigue • joint pain • swelling
Clinical Procedure: —
Specialty: General and Internal Medicine • Rheumatology

Objective: Rare coexistence of disease or pathology

Background: Some patients who have recovered from acute infection with SARS-CoV-2 develop persistent symptoms that
have been termed post-COVID syndrome (PoCoS). PoCoS can affect the musculoskeletal system, with arthral-
gia and myalgia being common. Preliminary evidence suggests that PoCoS is an immune-mediated condition
that not only predisposes but also precipitates pre-existing inflammatory joint diseases such as rheumatoid
arthritis and reactive arthritis. Here, we describe a series of patients who presented to our Post-COVID Clinic
and were found to have inflammatory arthritis (reactive and rheumatoid arthritis).
Case Reports: We present 5 patients who developed joint pain several weeks after recovery from acute SARS-CoV-2 infection.
These patients were seen in our Post-COVID Clinic and came from locations across the United States. All 5 pa-
tients were women, with age of diagnosis of COVID-19 disease between 19 and 61 years (mean 37.8 years).
All patients presented with joint pain as the primary concern to the Post-COVID Clinic. Abnormal joint imaging
was present in all patients. Treatments varied and included non-steroidal anti-inflammatory drugs, acetamin-
ophen, corticosteroids, immunomodulators (golimumab), methotrexate, leflunomide, and hydroxychloroquine.
Conclusions: COVID-19 disease is a potential cause of inflammatory arthritis, with both rheumatoid arthritis and reactive
arthritis demonstrated in our PoCoS population. Care must be taken to identify these conditions, as there are
treatment ramifications.

Keywords: COVID-19 • Arthritis • Arthritis, Reactive • Arthritis, Rheumatoid • Post-Acute COVID-19 Syndrome

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Rheumatoid arthritis and reactive arthritis in long COVID
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Background not diagnostic of a disease state, the presence of these auto-

Like many other upper respiratory infections (URIs), infection
with SARS-CoV-2, the virus that causes COVID-19 disease, can
manifest with a variety of symptoms, including fevers, chills,
arthralgia, myalgia, cough, nasal congestion, abdominal pain,
nausea, and vomiting [1]. However, a significant number of pa-
tients have persistent symptoms after resolution of the acute
phase of the infection. These persistent symptoms have been
given a number of names, including post-acute sequelae of
SARS-CoV-2 infection, long COVID-19, long haulers, and post-
COVID syndrome (PoCoS) [2-4].
As with other viral URIs, musculoskeletal symptoms frequently
occur during COVID-19 disease, with a spectrum of joint symp-
toms ranging from arthralgia to spurious and chronic arthri-
tis [5,6]. The incidence of inflammatory arthritis in patients who
have had COVID-19 is not known, but it has been established
that viruses causing URIs (coronavirus, parainfluenza virus, in-
fluenza virus, metapneumovirus) coincide with an increased
rate of development of rheumatoid arthritis (RA) [7]. Multiple
studies have now reported autoantibodies in patients with
COVID-19 disease (anti-cardiolipin, anti-beta 2 glycoprotein
I, anti-citrullinated protein [CCP] antibody, rheumatoid factor)
are associated with many autoimmune conditions, including
Kawasaki-like disease, systemic lupus erythematosus, autoim-
mune hemolytic anemia, Guillain-Barre syndrome, and multi-
ple sclerosis [8]. Although the mere presence of antibodies is
antibodies does highlight the immune dysregulation caused
by COVID-19 disease [9].
Reactive arthritis (ReA) is a disease process usually affecting
patients under 50 years of age. The joint inflammation is usual-
ly preceded by a genitourinary infection (Chlamydia trachoma-
tis) or a gastrointestinal infection (often Salmonella, Shigella,
Yersinia, Campylobacter, or Clostridium difficile). However, some
viral infections, including HIV, have also been attributed as eti-
ologic agents of ReA. Recent reports have identified patients
who developed inflammatory arthritis after coronavirus with
negative serological markers for RA and synovial fluid evalua-
tion, excluding bacterial infection or crystalline arthropathies,
which supports the likelihood of coronavirus infections being
associated with ReA [10,11]. Approximately 1% of all cases of
acute inflammatory arthritis are estimated to occur after viral
URIs, most commonly in women and older patients [12]. Based
on this data, COVID-19 has been proposed as a risk factor for
the development of RA and ReA [13].
In this case series, we describe 5 patients (Table 1) who were
evaluated in our Post-COVID-19 Care Clinic (PCOCC) and were
found to have inflammatory arthritis, including ReA and RA.

Table 1. Characteristics of our patient population.

COVID Rheumatologic Laboratory Reference

Age (Sex) Imaging findings
diagnosis symptoms onset tests range
Anti-CCP 23.3 (range <20) NM scan: bilateral knees, mid feet,
CRP 8.5 (range <8) 5th MTP left, right elbow, right wrist,
45 (Female) 8/2021 9/2021
RF 120 (range <15) left 5th PIP joint,
IL-6 5.6 (range <1.8) 1st right IP joint
D-dimer 908 (range <500) MRI: Left hand/wrist, radiocarpal,
46 (Female) 11/2020 5/2021
IL-6 102 (range <1.8) midcarpal, 1st-5th CMC joint

ESR 41 (range 2-22)

NM scan: right hip, right knee, both
D-dimer 610 (range <500)
54 (Female) 8/2021 12/2021 shoulders and bilateral radiocarpal
CRP 28.6 (range <8)
joint
IL-6 6.5 (range <1.8)

NM scan: 1st left MTP joint and

IL-6 9.7 (range <1.8)
61 (Female) 11/2020 12/2020 bilateral ankles, knees, hips, shoulders,
D-dimer 3744 (range <500)
elbows, wrists
ANA 1: 640 (negative <1: 80) NM scan: left hindfoot/ankle, bilateral
19 (Female) 2/2021 4/2021
Scl-70 1.5 (range <1) knees

NM scan = nuclear medicine joint scan (sodium pertechnetate Tc 99m injection (TECHNETIUM Tc-99m, 22 millicurie).
ANA – antinuclear antibody; CMC – carpometacarpal; CRP – C-reactive protein; ESR – erythrocyte sedimentation rate; IL – interleukin;
IP – interphalangeal; MRI – magnetic resonance imaging; MTP – metatarsophalangeal; PIP – proximal interphalangeal; NM – nuclear
medicine; RF – rheumatoid factor.

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Rheumatoid arthritis and reactive arthritis in long COVID
© Am J Case Rep, 2023; 24: e939870
Case Reports
Case 1
A 45-year-old highly functional woman with a significant past
medical history of morbid obesity (body mass index 48 kg/m2),
tobacco use, degenerative joint disease of the hip, and hip re-
placement developed anosmia and dysgeusia and tested pos-
itive for SARS-CoV-2 infection by polymerase chain reaction
(PCR) in the fall of 2021. Her condition progressed and she
developed fatigue, fever, and weakness, which eventually re-
solved after 3 weeks. She did not receive COVID-19-directed
therapy. Rapid antigen testing 3 weeks later was negative.
Four weeks after her COVID-19 symptoms had abated, she de-
veloped sudden onset of severe right wrist pain and swelling.
A
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She went to the Emergency Department, where initially she
was thought to have gout. She proceeded to develop joint pain
in the knees, shoulders, and hands, with associated morning
stiffness. Eventually, she was seen by a rheumatologist for
her severe joint pain, which was causing sleep disturbance.
On laboratory test results, a positive rheumatoid factor and
elevated anti-CCP antibodies were noted. As a result, the pa-
tient was prescribed a course of steroids, which provided sig-
nificant relief of her symptoms. She was trialed on methotrex-
ate (unknown dosage); however, she had significant adverse
effects, so she was transitioned to golimumab infusions (in-
travenously every 8 weeks) in February 2022. The golimum-
ab infusions and the prednisone (10 mg daily) helped but did
not resolve her symptoms completely. At the time of her visit
to our PCOCC, 3 months after starting golimumab, she report-
ed a 70% to 80% improvement in her symptoms.
On physical examination, she did not seem to be in any acute
distress. The patient did endorse fatigue and a weight gain
of more than 4.5 kg in the last few months, which was most
likely related to the corticosteroid therapy. In her review of
systems, she reported swelling in her legs and feet, palpita-
tions, abdominal pain, constipation, arthralgia, back pain, pain
and stiffness in the joints, joint swelling, and myalgia/muscle
stiffness. The patient’s physical examination did not show her
to have any clubbing, cyanosis, or edema in her extremities.
There was no rash or suspicious lesion found on the skin ex-
amination. Although her joints did have genu valgus deformi-
ties, mild Heberden and Bouchard’s nodes were present. The
patient did have tenderness of the right elbow, with resisted
wrist flexion mainly along the lateral epicondyle. The bilateral
Figure 1. Nuclear medicine scan showing increased radio tracer
uptake of case 1. (A) Bilateral knees. (B) Bilateral
wrists. (C) Left foot.
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knees had crepitus, with a decreased range of motion. There
was no synovitis of the hands, wrists, elbows, shoulders, hips,
knees, ankles, or toes. The patient’s vital signs were normal,
with blood pressure of 125/79 mm Hg and pulse of 70 beats per
min. She was afebrile. Her body mass index was 48.54 kg/m2.
A laboratory workup was significant, with a platelet count
slightly elevated at 391/L (range 157-371), white blood cell
count elevated at 10.0 (range 3.4-9.6), and lymphocytes ele-
vated at 3.56/L (range 0.95-3.07). Her D-dimer was elevated
at 1139 ng/mL (range <500), and her C-reactive protein (CRP)
level was slightly elevated at 8.5 mg/L (range <8). Interestingly,
her anti-CCP antibodies were slightly elevated at 23.3 units
(range <20), her rheumatoid factor was substantially elevat-
ed at 120 international units (IU)/mL (range <15), and her in-
terleukin (IL)-6 was elevated at 5.6 pg/mL (range <1.8). Her
severe SARS-CoV-2 nucleocapsid antibody test was positive,
consistent with prior SARS-CoV-2 infection.
Her nuclear medicine (NM) joint scan demonstrated increased
periarticular radiotracer uptake involving the bilateral knees,
bilateral mid feet, left fifth metatarsophalangeal joint, right el-
bow, left greater than right wrist, left fifth proximal interpha-
langeal joint, and the first right interphalangeal joint, consis-
tent with synovitis (Figure 1). The patient was evaluated by
our rheumatologist, who recommended the tapering of pred-
nisone to better evaluate her symptoms of inflammatory ar-
thritis. As per the last follow-up by our physician, the patient
unfortunately continued to experience some of her long COVID
symptoms but not specifically the arthritis.
Case 2
A 46-year-old previously healthy woman initially acquired
COVID-19 disease in November 2020, which was character-
ized by an acute course of headaches, body aches, chills, and
fatigue that lasted for 7 to 10 days and did not require any
COVID-19-directed therapies or hospitalization. Approximately
6 to 8 weeks later, she began to experience upper thoracic
back pain and chest pain. Computed tomography imaging of
the chest demonstrated clear lungs and no concern for a pul-
monary embolus. Of note, the patient was vaccinated with the
Moderna vaccine, obtaining her 2 doses in February and April
of 2021, along with a booster in November 2021. In the sum-
mer of 2021, 7 months after her first episode of COVID-19,
she began to experience pain in her neck, jaw, left wrist, and
legs. She subsequently developed bilateral Baker cysts, which
ruptured in December 2021. In January 2022, she had her sec-
ond bout of COVID-19, and the pain in her left wrist, both her
knees, and legs became much more pronounced. She addition-
ally reported a weight loss of 4.5 kg over the prior 6 months.
Review of her outside medical records revealed a positive an-
tinuclear antibody (ANA, 1: 320), with a negative extractable
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nuclear antibody panel, rheumatoid factor, and anti-CCP anti-
bodies. The patient continued to have bilateral knee pain, with
occasional swelling, right ankle pain, left wrist pain and swell-
ing, upper thoracic/lower neck pain, and chest pain on inspi-
ration. She denied skin rash, oral ulcers, alopecia, photosensi-
tivity, malar erythema, dactylitis, red eyes, or proximal muscle
weakness. Her symptoms were worse in the morning and im-
proved with activities. Physical examination revealed left wrist
swelling along with tenderness to palpation in the left wrist,
as well as near the pes anserine bursa of both knees. She tried
celecoxib (100 mg daily) and meloxicam (15 mg daily) with-
out any benefit. She was also started on hydroxychloroquine
200 mg by a rheumatologist for the past 2 to 3 months for
the possibility of seronegative RA, without significant benefit.
When she was seen at our institution in May 2022, she had
an elevated D-dimer level of 908 ng/mL (range <500), elevat-
ed IL-6 level of 10.2 pg/mL (range <1.8), and negative anti-CCP
antibodies, rheumatoid factor, and human leukocyte antigen
(HLA) B27. An NM joint scan showed increased periarticular
radiotracer uptake involving the bilateral knees, right ankle,
and left wrist. Magnetic resonance imaging of her left hand
and wrist showed marked enhancing synovitis with extensive
effusions throughout the wrist, including the radiocarpal, mid-
carpal, and first to fifth carpometacarpal joints, associated with
scattered joint erosions in the wrist and moderate enhanc-
ing tenosynovitis in the flexor compartment. Given her poor
response to nonsteroidal anti-inflammatory drugs (NSAIDs)
alone, these therapies were discontinued, and she was start-
ed on methotrexate 25 mg/mL injection weekly, along with fo-
lic acid 1 mg daily by our rheumatologists.
Case 3
A 54-year-old woman with no significant medical history devel-
oped flu-like symptoms in August 2021, associated with fatigue,
body aches, loss of taste and smell, and a reduced appetite. She
was never formally tested for COVID-19 but self-isolated at home
for 10 days. In early September 2021, she developed abdominal
pain, facial rash, and low back pain. Medical evaluation at that
time was significant for elevated transaminase levels and steato-
sis on abdominal ultrasound. A liver biopsy in November 2021
showed “severe acute panacinar hepatitis with areas of paren-
chymal collapse with no definitive fibrosis identified”. Between
November and December 2021, as her liver function levels were
improving, she started developing significant joint pain and swell-
ing. Her knees were most prominently affected, to the point where
she needed to use crutches to walk. She was seen by her local
rheumatologist, had a reportedly negative workup, and was start-
ed on prednisone 30 mg in January 2022. The follow-up eryth-
rocyte sedimentation rate (ESR) and CRP level in March 2022
were in the normal range, along with a negative ANA result. Of
note, the patient did receive COVID vaccination in April of 2022.
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© Am J Case Rep, 2023; 24: e939870
Her physical examination at our institution did not show any
notable synovitis; however, she did have tenderness to palpa-
tion on both her hands, particularly on the right. Upon further
evaluation at our institution in May 2022, she had an elevat-
ed ESR of 41 (range 2-22 mm/h), D-dimer level of 610 (range
<500), CRP level of 28.6 (<8 mg/h), and IL-6 level of 6.5 (range
<1.8). However, her ANA and anti-CCP antibody test results
were both negative. Given the timing of her infection and clin-
ical symptoms, her viral URI was thought to have been most
likely COVID-19. An NM joint scan showed a mildly increased
radiotracer uptake in the right hip, right knee, both shoul-
ders, and bilateral radiocarpal joints, which was compatible
with active inflammation. She was continued on her predni-
sone (40 mg daily), as it was providing some relief. The pred-
nisone was tapered and eventually stopped later that month
when her joint pain resolved. Two months later, she presented
to the Rheumatology Clinic with concerns of right knee pain,
which based on the evaluation, was likely mechanical in nature.
Case 4
A 61-year-old woman with type 1 diabetes mellitus and hyper-
tension tested positive for COVID-19 in November 2020, with
initial symptoms of fevers, chills, myalgia, anosmia, and dys-
geusia. One month later, she developed post-exertional mal-
aise and myalgia and arthralgia, predominantly in her hands,
shoulders, and knees (more so on the right side). She addition-
ally reported that the pain in her hands was associated with
numbness. She trialed conservative therapy, including heat, ice,
stretching, baths, ibuprofen, gabapentin, and opioids, but these
therapies did not provide significant relief. She was evaluat-
ed by the Rheumatology Clinic, and her IL-6 level was elevat-
ed at 9.7 (range <1.8), and D-dimer level was elevated at 3744
(range <500), but the remainder of her inflammatory markers
were normal. The NM joint scan showed increased radiotrac-
er uptake in the first left metatarsophalangeal joint and bilat-
eral ankles, knees, hips, shoulders, elbows, wrists, and hands,
consistent with active inflammation. The patient was started
on a trial of low-dose prednisone (15 mg/day), with signifi-
cant improvement in pain in all her joints within a few days.
A trial of methotrexate and leflunomide as steroid-sparing
agents was unsuccessful due to intolerable adverse effects.
Hydroxychloroquine was tolerated, but prednisone was un-
able to be weaned below 10 mg/day due to increased pain
and stiffness. At present, the patient continues on 10 mg of
prednisone along with hydroxychloroquine, with good con-
trol of symptoms.
Case 5
A previously healthy 19-year-old woman was clinically diag-
nosed with COVID-19 in February 2021, with symptoms of
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dyspnea, lightheadedness, dizziness, chills, myalgia, conges-
tion/rhinorrhea, nausea, vomiting, abdominal pain, and fa-
tigue, which lasted for 3 weeks. Six to eight weeks later, she
developed persistent joint pain in her bilateral knees, shoul-
ders, ankles, hips, low back, neck, and wrists, which was in
stark contrast to previous athletic training injuries that she
rapidly recovered from.
Her physical examination in our clinic revealed her to have ten-
derness over her patellar tendon, but no synovitis was noted
over her wrists or ankles. There was slight puffiness around her
left ankle, with no notable tenderness. Her skin examination
did not reveal any sclerodactyly or telangiectasia. When she
was evaluated at our PCOCC, her ANA was elevated at 1: 640
(negative <1: 80) in a homogeneous pattern, and her Scl-70
level was slightly elevated at 1.5 (negative <1). The remainder
of her laboratory test results were unremarkable, including an-
tibodies to double-stranded DNA, complement, IL-6, HLA-B27,
ESR (5 mm/h), CRP (<3 mg/L), and D-dimer. Her NM joint scan
showed increased radiotracer uptake in her left hindfoot/an-
kle and bilateral knees, consistent with synovitis. The patient
was seen in the Rheumatology Clinic, was started on cortico-
steroids, and had a rapid clinical response. She continues a
low-dose tapering regimen of corticosteroid (methylprednis-
olone 4 mg daily) with her arthritic symptoms being kept at
bay. Following this regimen, the patient states that this is the
best that she has felt in years and now uses an NSAID (meloxi-
cam 15 mg daily) as needed.
Differential Diagnosis
The differential diagnosis for the patients in our case series
with arthralgia and joint swelling after SARS-CoV-2 infection
included osteoarthritis, viral polyarthritis, and autoimmune
diseases, including ReA, RA, systemic lupus erythematosus,
Sjogren syndrome, dermatomyositis, fibromyalgia, and mixed
connective tissue disorder.
Even though all the symptoms for the patient in case 1 were
not classical for RA, her inflammatory markers were elevated,
and she had a positive rheumatoid factor and elevated anti-
CCP antibodies, which were suggestive of RA [14]. Given her
associated fatigue and poor sleep, the concern for chronic fa-
tigue syndrome/fibromyalgia also arose, but she did not meet
the diagnostic criteria for these syndromes. With the overlap-
ping signs and symptoms of RA with various rheumatologic,
dermatologic, endocrine pathologies, it is of the utmost im-
portance to evaluate alternative diagnoses. Categorically rul-
ing out alternative diagnoses with the help of serology tests
and imaging is crucial.
To date, no validated diagnostic criteria or definitive labora-
tory test for ReA exists. The diagnosis of ReA is usually based
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on a clinical assessment following the exclusion of other dif-
ferential diagnoses. In our cases 2, 3, 4, and 5, the diagnosis
of ReA was made based on clinical findings and the exclusion
of other inflammatory arthritis, based on blood workup and
imaging (NM joint scan).
Discussion
Viral infections are a potential etiologic factor for the devel-
opment of inflammatory arthritis and other forms of autoim-
mune arthritis, with multiple proposed pathophysiologic mech-
anisms [15]. These include (1) “molecular mimicry”, which
occurs when a viral antigen mimics a host and activates cross
reactive T cells; (2) “epitome spreading”, when tissue dam-
age results from specific T-cell activation or direct virus-me-
diated host tissue destruction causing activation of autoreac-
tive T cells and release of cell antigens into the inflammatory
movement; (3) “super antigens” activating a wide range of
nonspecific T cells; (4) “bystander activation” when autoreac-
tive T cells are activated due to the release of cytokines when
the virus targets the immune system; and (5) host antigens re-
leased from certain tissues during a virus-targeted immune re-
sponse [7,8]. Additionally, local airway inflammation and neu-
trophil extracellular trap formation have been hypothesized as
driving factors for anti-CCP antibody production in the lungs
of first degree relatives with RA [16]. Neutrophil extracellular
trap-derived proteases can cause the release of peptidylargi-
nine deiminases, which could be pathogenic in RA. The pres-
ence of neutrophil extracellular traps has also been shown in
the lung tissue and serum of patients with COVID-19 [17,18].
Genetic, environmental, hormonal, and immunologic factors
have been implicated in the pathogenesis of RA and ReA. The
strongest genetic risk factor for RA and ReA is the HLA class,
accounting for 60% of genetic susceptibility for patients with
RA and associated with a higher risk of chronicity [19,20].
Subsequently, the HLA-DRB 1 genotype is encountered in
most cases of HLA-associated RA [21]. Analysis of HLA geno-
types could prove useful in further work exploring the risk of
inflammatory arthritis after COVID-19. Environmental factors,
such as tobacco use, further increase the risk of immune re-
action and production of anti-CCP antibodies [22]. Except for
the patient in case 1, none of our other patients were current
or previous users of tobacco in any form. The patient in case
1 used tobacco via traditional and electronic cigarettes, which
both may have been predisposing to her inflammatory arthri-
tis and contributing to its severity.
Our case series adds to a growing body of literature re-
porting the development of RA or ReA following COVID-19
[1,10,11,13,19,23-25]. In these cases, the severity of COVID-19
disease ranged from asymptomatic to critical, suggesting that
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Rheumatoid arthritis and reactive arthritis in long COVID
© Am J Case Rep, 2023; 24: e939870
there is no relationship between COVID-19 severity and arthri-
tis risk. This relationship is similar to that seen in PoCoS, in
which, while there is a higher incidence of PoCoS in patients
with severe COVID-19, most cases seen had mild or moder-
ate COVID-19, owing to the sheer number of patients in this
category [26]. In our case series, our patients would be clas-
sified as having had mild or moderate COVID-19, as they did
not require admission or supplemental oxygen.
ReA has been associated with gastrointestinal and genitouri-
nary infections. Notably, gastrointestinal manifestations have
been reported in upwards of 12% of COVID-19 patients [27,28].
It has been surmised that the gastrointestinal system may
serve as a secondary site for coronavirus due to the expres-
sion of angiotensin converting enzyme-2 receptors in the gas-
trointestinal tract, which would support its role in the devel-
opment of ReA [29]. Thus far, no genitourinary manifestations
have been clearly associated with SARS-CoV-2 infection; thus,
it is difficult to establish a plausible molecular mechanism for
ReA by this pathway.
The rheumatoid factor level in the patient in case 1, checked
8 months after her SARS-CoV-2 infection, was markedly ele-
vated at 120 IU, and her anti CCP levels were mildly elevated
at 23.3 U. While her rheumatoid factor and anti-CCP antibody
levels prior to the SARS-CoV-2 infection had not been tested,
they continued to increase over 2 time points after SARS-CoV-2
infection. In the case report by Perrot et al, their patient’s anti-
CCP antibody levels were already detectable when the patient
had tested positive for SARS-CoV-2; however, her anti-CCP ti-
ters had increased substantially since the time she developed
arthritis. It was postulated that this increasing anti-CCP titer
trend was indicative of the spread of the epitope prior to the
onset of clinical joint disease, suggesting that COVID-19 might
have precipitated an initial flare of RA in their patient [25].
Unfortunately, in the case of ReA, no existing diagnostic test
can be performed to follow disease activity, apart from follow-
ing clinical symptoms over time. There is a possibility that in-
flammatory arthritis in our case series could have been coin-
cidentally related to the SARS-CoV-2 infection; however, the
timeline, whereby one of our patients continued to have ele-
vated rheumatoid factor and anti-CCP levels even 8 months
after the infection had subsided, might speak to the fact that
the arthritic process could have been precipitated by the SARS-
CoV-2 infection. We do acknowledge that whereas not every
case of inflammatory arthritis (ReA or RA) that is diagnosed
after SARS-CoV-2 infection is necessarily related to the SARS-
CoV-2 infection, there is a theory that SARS-CoV-2 infection
could be resulting in an inflammatory response, thereby re-
sulting in a flare of arthritis in these patients [25].
Synovial fluid examination was not performed in any of our
patients. In the case report by Gasparotto et al, synovial fluid
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Yadav S. et al:
Rheumatoid arthritis and reactive arthritis in long COVID
© Am J Case Rep, 2023; 24: e939870
analysis revealed inflammatory cells with polymorphonucle-
ar predominance, with a negative RT-PCR for COVID-19, fur-
ther supporting the hypothesis that this is an immune-medi-
ated process [30]. Similarly, in the case reported by Lim et al,
in their patient with ReA, synovial fluid analysis was negative
for crystals, Gram stain, N. gonorrhoeae bacteria, and C. tracho-
matis [31]. The low prevalence of inflammatory arthritis after
COVID-19 has also been partially attributed to widespread use
of drugs with anti-inflammatory effects, such prednisone for
the treatment of COVID-19 for certain severe cases, which may
prevent or minimize the inflammatory joint manifestations [30].
Terracina et al report on a 55-year-old man with well-controlled
non-erosive, seropositive RA at 2 years of clinical remission
who developed an acute flare of his RA subsequent to the sec-
ond dose of his mRNA COVID-19 vaccine. The authors postu-
lated that this flare was secondary to an immune response
to a component of the vaccine. The vaccine contained mRNA
encoding for the SARS-CoV-2 spike protein plus other compo-
nents that stabilize the vaccine in the circulation and promote
its uptake into the cell by endocytosis. It was speculated that
one of these components might have had a nonspecific adju-
vant effect, or there could have been molecular mimicry be-
tween the viral spike protein and the patient’s immunoglobu-
lins, resulting in the symptom flare [32-34]. Given the immune
pathophysiology of ReA, it is likely that susceptible individu-
als could flare similarly after vaccination.
Inflammatory arthritis was identified in our patients via an in-
creased uptake of the radioactive isotope on NM joint scans.
In the existing literature, imaging studies in patients with in-
flammatory arthritis demonstrate findings suggestive of non-
specific inflammation in the affected joints, including synovial
tissue thickening, increased vascularity, and joint effusion [35].
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Conclusions
Persistent arthritis after COVID-19 has been referred to as post-
COVID arthritis, post-viral arthritis, and post-COVID hyperin-
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Main Institute for the Cases
Mayo Clinic, Rochester, MN, USA.
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