Individuals with inflammatory rheumatic disease require special consideration with
regard to coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2). Many of these individuals are considered at-risk
for serious infections due to their immunocompromised state resulting from their underlying
immune conditions and use of targeted immune-modulating therapies such as biologics.1,
2, 3, 4 However, some disease-modifying drugs commonly used to treat rheumatic diseases,
such as hydroxychloroquine, are being investigated as potential therapies for COVID-19.
5
Other commonly used therapies, such as biologics targeting interleukin (IL)-6 (eg,
tocilizumab, sarilumab) and IL-1 (eg, anakinra), are being assessed in patients with
COVID-19 and who have subsequently developed pathological immune responses, including
cytokine storm (eg, reactive haemophagocytic lymphohistiocytosis).
6
Whether background immunosuppressive medications put individuals with rheumatic disease
at an increased or decreased risk for severe SARS-CoV-2 infection is unknown,
7
and evidence is lacking to guide treatment decisions. A general understanding of COVID-19
characteristics in this population is urgently needed to inform management guidelines
and identify high-risk individuals during the pandemic.
The need for data to answer these key clinical questions was quickly realised and
coordinated on a global scale by rheumatologists, researchers, and patients with rheumatic
diseases. Despite the recognised track-record of high-quality observational drug safety
research in rheumatology within multiple national biological registries,
8
immediate data on COVID-19-specific outcomes would need to be collected to address
this demand. Therefore, the international rheumatology community mobilised at an unprecedented
pace to create the COVID-19 Global Rheumatology Alliance. In less than 1 week, the
COVID-19 Global Rheumatology Alliance successfully developed online portals and case
report forms to enable health-care providers around the world to enter information
on individuals with rheumatic disease who have been diagnosed with COVID-19.
Registry data elements include provider name, city, country, and clinic, and individual
patient-level sociodemographic information, including age, sex, race, and ethnicity.
Data regarding rheumatic disease are captured, including medications before COVID-19
diagnosis, disease activity, and comorbidities. Information on COVID-19-related illness
includes diagnosis date, symptoms, treatment, and outcomes, such as admission to hospital
and maximum level of care (eg, need for supplemental oxygen, invasive ventilation).
Laboratory results for other co-infections, IL-6 concentrations, leucopenia, and more
are also collected, if available.
Due to international data legislation, in particular, the European General Data Protection
Regulations, parallel data entry points (one limited to European League Against Rheumatism
[EULAR]-participating countries, the other limited to sites globally have been launched.
Both data entry points link to secure RedCap survey platforms hosted by The University
of Manchester (Manchester, UK), and the University of California, San Francisco (UCSF;
San Francisco, CA, USA), where providers submit data on individuals with rheumatic
disease who have been diagnosed with COVID-19. Individual patient consent is not required
for this registry, which was determined “not human subjects research” by the UK Health
Research Authority, The University of Manchester, the US Federal Guidelines by UCSF,
and several other institutions.
As of April 1, 2020, 110 individuals with rheumatic disease who have been diagnosed
with COVID-19 are included from six continents: Europe, North America, South America,
Asia, Africa, and Oceania; a summary of data associated with these individuals is
shown in the table
.
Table
Demographic and disease characteristics of individuals with rheumatic disease diagnosed
with COVID-19 in the COVID 19 Global Rheumatology Alliance registry as of April 1,
2020
Cohort (n=110)
Sex
Female
79 (72%)
Male
31 (28%)
Aged >65 years
20 (18%)
Primary rheumatic disease*
Rheumatoid arthritis
40 (36%)
Psoriatic arthritis
19 (17%)
Systemic lupus erythematosus
19 (17%)
Axial spondyloarthritis
7 (6%)
Vasculitis
7 (6%)
Sjogren's syndrome
5 (5%)
Other
17 (15%)
Medications before diagnosis of COVID-19
Conventional synthetic DMARDs†
69 (63%)
Biological DMARDs‡
49 (45%)
JAK inhibitor
5 (5%)
NSAIDs†
28 (25%)
Glucocorticoids
27 (25%)
Other§
5 (5%)
Five most common COVID-19 symptoms at onset
Fever
87 (79%)
Cough
85 (77%)
Shortness of breath
55 (50%)
Myalgia
49 (45%)
Sore throat
41 (37%)
Admitted to hospital
39 (35%)
Died
6 (5%)
Five most common comorbid conditions
Hypertension
31 (28%)
Lung disease¶
22 (20%)
Cardiovascular disease
12 (11%)
Morbid obesity (BMI ≥40 kg/m2)
9 (8%)
Diabetes
9 (8%)
Data are n (%). COVID-19=coronavirus disease 2019. DMARD=disease-modifying antirheumatic
drug. NSAID=nonsteroidal anti-inflammatory drugs. JAK=Janus kinase. BMI=body-mass
index.
*
Individuals could have more than one rheumatic disease diagnosis; other included (all
with n <5): inflammatory myopathy, ocular inflammation, other inflammatory arthritis,
polymyalgia rheumatica, sarcoidosis, systemic sclerosis, osteoporosis, psoriasis,
isolated pulmonary capillaritis, gout, and autoinflammatory disease.
†
Conventional synthetic DMARD medications included antimalarials, azathioprine, cyclophosphamide,
ciclosporine, leflunomide, methotrexate, mycophenolate mofetil, mycophenolic acid,
sulfasalazine, and tacrolimus.
‡
Biological DMARDs included abatacept, belimumab, CD20 inhibitors, IL-1 inhibitors,
IL-6 inhibitors, IL-12 and IL-23 inhibitors, IL-17 inhibitors, and tumor necrosis
factor inhibitors.
§
Other included antifibrotics, apremilast, intravenous immunoglobulin, thalidomide
or lenalidomide, and other not specified.
¶
Chronic obstructive pulmonary disease, asthma, interstitial lung disease, or other
not specified.
We present proof-of-principle that, with global cooperation, the rapid collection
of data during an international crisis is possible. Within 1 week of launching the
registry, rheumatology providers from around the world have submitted data on more
than 100 cases, allowing very preliminary characterisation and rapid dissemination
of information regarding COVID-19 in individuals with rheumatic disease. Over time,
the registry aims to examine differences in severity of outcomes by sociodemographic
and rheumatic disease characteristics, medications taken before diagnosis of COVID-19,
and medications administered on diagnosis. These data will serve to inform treatment
strategies and better characterise individuals at increased risk of infection.
The strengths of the COVID-19 Global Rheumatology Alliance registry include global
representation of individuals with rheumatic disease with COVID-19, which increases
the power of the evidence base to examine important risk factors and outcomes. We
expect that a major contribution of the COVID-19 Global Rheumatology Alliance will
be rapid dissemination of information, since existing national patient registries
might be less equipped to capture data on a global scale, given fixed timepoints and
restrictions on consent of new individuals.
The registry is not without limitations, including a potential selection bias towards
more severe cases, because in many countries only individuals with severe symptoms
are being tested for COVID-19. Rheumatologists reporting cases are also under extreme
pressure to work outside of rheumatology and provide front-line medical care to all
patients with COVID-19 and might be unable to report cases, or reporting might be
delayed. Duplicate entries might occur across different providers, although our data
analytics teams carefully examine and address data quality on a regular basis. Also,
despite including individuals from across the world, specific adjusted analyses might
not be possible due to sample size. Finally, as the whole denominator of individuals
with rheumatic diseases who acquire COVID-19 is unknown, the database will be unable
to provide accurate estimates of the risk of specific outcomes across the entire rheumatic
disease population or in association with specific treatments. With time, existing
patient registries and administrative databases will provide these data, but likely
not until the current pandemic has ended, thus strengthening the current and critical
role of this database.
In summary, the COVID-19 Global Rheumatology Alliance represents the commitment of
rheumatologists to generate rapid data to help inform the care of individuals with
rheumatic disease and those using immunomodulating therapies. Information from this
database will provide timely and responsive real-world data where large literature
gaps exist, informing providers of treatment patterns for individuals diagnosed with
COVID-19, and offering a better understanding of possible risk factors associated
with severe outcomes in the rheumatic disease population.