Argentinian Registry of Patients With Rheumatic Diseases and COVID-19 Infection
Conditions: Rheumatic Diseases
Sponsor: Sociedad Argentina de Reumatologia

 
 
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Impact of the Treatment with Immunomodulatory and 
Immunosuppressive Drugs in Patients with  
Rheumatic Diseases and COVID-19 
 
 
 
 
Unidad de Investigación de la Sociedad Argentina de Reumatología (UNISAR) 
(Research Unit of the Argentine Society of Rheumatology) 
 
 
 
 
 
 
STUDY PROTOCOL 
Version 3.0 
 
 
Principal Investigator: Guillermo J. Pons-Estel. 
Scientific Committee: Enrique R. Soriano, María Celina de la Vega,  
Bernardo A. Pons-Estel, Karen Roberts and Rosana Quintana. 
Argentine Rheumatology Society representative: Cesar Graf, President. 
 
 
 

 
 
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TABLE OF CONTENTS 
INTRODUCTION ............................................................................................................................ 3 
JUSTIFICATION OF THE STUDY ................................................................................................ 4 
HYPOTHESIS OF THE INVESTIGATION..................................................................................... 5 
OBJECTIVES ................................................................................................................................. 5 
PRIMARY OBJETIVE ........................................................................................................................... 5 
SECONDARY OBJECTIVES ............................................................................................................... 5 
ETHICAL ASPECTS ...................................................................................................................... 6 
ADVERSE EVENT (AE), PREGNANCY EXPOSURE, AND INCIDENT REPORTING ............... 7 
METHODOLOGY ........................................................................................................................... 8 
DESIGN .................................................................................................................................................. 8 
TARGET POPULATION ....................................................................................................................... 8 
ELIGIBILITY CRITERIA ........................................................................................................................ 8 
SAMPLE SIZE CALCULATION ........................................................................................................... 8 
RECRUITMENT ..................................................................................................................................... 9 
VARIABLES AND DEFINITIONS ...................................................................................................... 10 
DATA COLLECTION ........................................................................................................................... 10 
CODING ................................................................................................................................................ 10 
QUALITY CONTROL .......................................................................................................................... 10 
PERIODIC REPORTS ................................................................................................................. 11 
STATISTICAL CONSIDERATIONS ............................................................................................ 12 
NAMES AND CONTACT DETAILS ............................................................................................ 13 
TIMETABLE ................................................................................................................................. 14 
BIBLIOGRAPHY .......................................................................................................................... 15 
APPENDIX 1. RHEUMATIC DISEASES. .................................................................................... 17 
APPENDIX 2. IMMUNOMODULATORY AND/OR IMMUNOSUPPRESSIVE CHRONIC 
TREATMENTS. ............................................................................................................................ 18 
APPENDIX 3. VARIABLES. ........................................................................................................ 20 
 
 
 
 
 

 
 
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INTRODUCTION 
 
COVID-19 (Corona Virus Disease-2019) is an infectious disease produced by a 
novel strain of a beta-coronavirus RNA, called SARS-CoV-2 according to the 
International Committee on virus taxonomy; the name was given due to  the 
similarities between this virus and  the one that causes severe acute respiratory 
syndrome (SARS) (1). In December 2019, the first outbreak of cases of severe 
pneumonia caused by this coronavirus emerged in Wuhan, a city in the Hubei 
province of China (2). After an increasing number of cases and a rapid 
geographical spread worldwide, the World Health Organization (WHO) declared 
it to be a pandemic on March 11, 2020 (3).  
Person-to-person transmission of the virus occurs through droplets that are 
spread by coughing, sneezing, or talking and can be breathed in, or contaminate 
surfaces that people touch. The virus usually enters through the airways, mouth 
or conjunctiva and replicates in the epithelial cells of the upper and lower 
respiratory tract (4). The spread is fast and each contaminated person usually 
infects around 2 to 4 people (5).  
Approximately 80% of the people who become infected suffer a mild form of the 
disease, 15% a severe form that will require hospitalization, and about 5% 
develop the most severe form (6). All people are susceptible to infection, however 
those with pre-existing comorbidities such as hypertension, obesity,  chronic lung 
disease, diabetes and/or cardiovascular disease and those with a weakened 
immune system appear to be more vulnerable to develop a more aggressive and 
fatal disease (7, 8). Rheumatic diseases, including systemic autoimmune 
diseases, are usually associated with a greater predisposition to viral infections, 
due to the intrinsic risk of the pre-existing disease and the iatrogenic effect of the 
immunosuppressive drugs used for their treatments (9, 10). Nevertheless, there 
is growing optimism, although still with a low level of scientific evidence, about 
the role that different immunomodulatory and immunosuppressive drugs used to 
treat rheumatic diseases, may have a beneficial effect in the treatment of acute 
respiratory distress syndrome (ARDS) associated with a cytokine storm, with 
endothelial dysfunction and disseminated intravascular coagulation (11-13). 
These treatments include antimalarials (14), colchicine (15), corticosteroids (16, 

 
 
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17), janus kinase inhibitors (18, 19) and biologic drugs such as anti-IL-1, anti-IL-
6, (20, 21), anti-IL-6r (22), and anti-TNF (23), among others (24-26). 
Internationally, a rheumatologist consortium or alliance has recently emerged 
with the aim of creating a global registry of patients with rheumatic diseases and 
COVID-19 (Global Rheum-COVID Registry - https://www.rheum-covid.org ) (27). 
At the local level, and due to the lack of information, the Argentine Society of 
Rheumatology (Sociedad Argentina de Reumatología - SAR) proposes to carry 
out a national registry of COVID-19 in patients with rheumatic diseases (SAR-
COVID) that aims to study the socio-demographic, clinical characteristics and 
outcomes of COVID-19 in this group of patients, and to compare them with the 
data obtained by the Global Rheum-COVID Registry.  
 
 
JUSTIFICATION OF THE STUDY 
 
The COVID-19 pandemic is a matter of great concern to rheumatologists 
because the majority of patients with rheumatic diseases, especially those with 
systemic autoimmune diseases, have abnormalities of the underlying immune 
system and are commonly treated with immunosuppressive therapies that may 
increase the risk of serious infections. However, at present, there is insufficient 
information to support this claim, and the extrapolation of these data to SARS-
CoV-2 infection is at least ambiguous due to the potentially protective role of 
immunomodulatory and immunosuppressive drugs in the control of a severe 
inflammatory response to infection.  
In the short time that we have been navigating this uncharted pandemic, its 
evolution over time is still unknown, therefore it is a priority to get real life 
information. A rheumatology COVID-19 registry to be made throughout Argentina 
and led by the SAR, who considers this project strategic, will enable the rapid 
collection of case information from physicians who treat patients with rheumatic 
diseases. This registry is designed to answer at least three important questions: 
a) what are the COVID-19 outcomes among patients with rheumatic diseases, 
particularly 
those 
with 
systemic 
autoimmune 
diseases 
treated 
with 
immunomodulatory and/or immunosuppressive therapies, in terms of harms or 
benefits?; b) what is the impact of genetic (ethnicity), sociodemographic (e.g. 

 
 
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socioeconomic status, level of education) and environmental factors 
(geographical areas) on the severity of patients affected by COVID-19?; c) what 
will be the interaction between coronavirus, systemic autoimmune diseases and 
immunomodulatory and/or immunosuppressive treatment in the short and longer 
term?. 
Finally, this real life registry will help the scientific community and entities that 
generate and finance health policies, to develop better strategies for the benefit 
of all patients with rheumatic diseases. 
 
HYPOTHESIS OF THE INVESTIGATION 
 
Patients with rheumatic diseases who are under chronic treatment with 
immunomodulatory and/or immunosuppressive drugs more frequently have an 
asymptomatic infection, a milder COVID-19 and lower mortality than patients with 
rheumatic diseases without immunomodulatory and/or immunosuppressive 
treatments.   
 
OBJECTIVES 
PRIMARY OBJETIVE 
• Evaluate through a national registry of patients with rheumatic diseases, 
chronically 
treated 
or 
not 
with 
immunomodulatory 
and/or 
immunosuppressive drugs, the course (disease presentation, evolution 
and mortality) of the SARS-CoV-2 infection. 
 
SECONDARY OBJECTIVES  
• Assess the protective effect of chronic treatment (three months or longer) 
with immunomodulatory and/or immunosuppressive drugs on the 
development of COVID-19. 
• Measure the impact of chronic treatment with immunomodulatory and/or 
immunosuppressive drugs on the development of severe forms of COVID-
19 (admission in intensive care unit -ICU, use of invasive mechanical 
ventilation) and mortality. 

 
 
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• Describe the impact of sociodemographic conditions on the COVID-19 
outcomes. 
• Assess the impact of coronavirus infection on the appearance of unusual 
or atypical manifestations of rheumatic disease, and on the development 
of a new associated autoimmune disease. 
• Evaluate the recovery rate of COVID-19 in patients with rheumatic 
diseases 
treated 
chronically 
with 
immunomodulatory 
and/or 
immunosuppressive drugs. 
• Assess the impact of coronavirus infection on the quality of life of patients 
with rheumatic diseases. 
• Evaluate the burden of both diseases (rheumatic diseases and COVID-
19) on the health system. 
• Contribute to the best international knowledge of COVID-19 through 
collaboration with the Global International Alliance Rheum-COVID 
Registry -https://www.rheum-covid.org 
 
ETHICAL ASPECTS 
 
This study will be conducted in accordance with the Good Clinical Practice (GCP) 
guidelines, the International Conference on Harmonization (ICH), and with the 
ethical principles established in the Declaration of Helsinki, the law 3301/09, and 
the guidelines of the local ethics committee. Personal identification data will be 
kept anonymous and protected according to the international and national 
regulations in order to guarantee confidentiality, in accordance with the Law on 
Protection of Personal Data No. 25.326 / 2000. 
The protocol, any amendment that arises and the informed consent of the 
patients, must be approved by the Research Ethics Committee “Dr. Claude 
Barnard”, from Rosario, Argentina, Argentina, prior to the initiation of the study. 
For the purposes of this project, only medical researchers will access patients' 
medical records in order to obtain the data required for the investigation, thus 
ensuring their confidentiality. The data extracted from the medical records will be 
downloaded into a database where the patient's first and last name will not 
appear, but their data will be anonymized with an identification number, sex and 
date of birth. 

 
 
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ADVERSE EVENT (AE), PREGNANCY EXPOSURE, AND INCIDENT 
REPORTING 
 
During the study all adverse events will be collected. The Investigators will assess 
information on adverse events, pregnancies and special situations at each patient 
visit during the course of the study and report them to the sponsor when one of 
the sponsor's drugs is involved.  
The investigators will: 
• Transfer to the sponsors in an ongoing manner reports of serious AEs, 
drug misuse or abuse and reports of drug exposure during pregnancy. 
• Transfer to the sponsor any other information that may suggest a change 
in the benefit-risk profile for the sponsor's drug, and where required, copies 
of Investigator Notifications for suspected unexpected serious adverse 
events (SUSAR) and copies of the Development Safety Update Report. 
 
The following is a list of events will be reported to the Sponsor within 24 hours 
after learning of the event, regardless of relationship to study drug: 
• Serious AEs  
• Adverse events of Special Interest (AESIs) 
• Pregnancies  
 
The investigators will report new significant follow-up information for these events 
to the sponsor immediately (i.e., no more than 24 hours after becoming aware of 
the information). New significant information includes the following: 
• New signs or symptoms or a change in the diagnosis. 
• Significant new diagnostic test results. 
• Change in causality based on new information. 
• Change in the event’s outcome, including recovery. 
• Additional narrative information on the clinical course of the event. 
• Investigators must also comply with local requirements for reporting 
serious adverse events to the local health authority and IRB/EC. 

 
 
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METHODOLOGY 
DESIGN 
SAR-COVID is a national, multicenter, prospective, observational longitudinal 
study (registry) of consecutive patients with diagnosis of rheumatic diseases (see 
appendix 1) treated or not with immunomodulatory and/or immunosuppressive 
drugs (see appendix 2) and SARS-CoV-2 infection (asymptomatic or COVID-19).  
TARGET POPULATION 
Patients  18 years of age with any rheumatic disease. 
ELIGIBILITY CRITERIA 
Inclusion Criteria   
• Age  18 years. 
• Patients with diagnosis of rheumatic diseases (treated or not with 
immunomodulatory and/or immunosuppressive drugs). 
• Patients with diagnosis of SARS-CoV-2 infection (past or present) with 
positive test for the virus SARS-CoV-2 from analysis of nasopharyngeal or 
oropharyngeal swab specimens (reverse transcriptase–polymerase-
chain-reaction assay) or by serology, independently of symptoms. 
Exclusion Criteria 
• Patients who do not wish to participate or are unable to give informed consent.  
 
SAMPLE SIZE CALCULATION 
This is a non-probability sampling study with enrollment of consecutive patients 
who meet the selection criteria.  
It is expected that 3,000 patients with COVID-19 and some rheumatic disease, 
who are cared for by rheumatologists in any of the 23 provinces of Argentina, will 
be enrolled in the SAR-COVID registry during the period from July 1 to December 
31, 2020. Twelve-month extension of the recruitment period will be applied if the 
expected number of patients is not achieved by the end of the inclusion date. 
 

 
 
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Two cohorts will be included: the first will enroll 1,500 patients treated with 
immunomodulatory and/or immunosuppressive drugs, and the second will enroll 
1,500 patients without immunomodulatory and/or immunosuppressive drugs. 
In Argentina, there are currently 31,000,000 inhabitants 18 years of age or older. 
Assuming, conservatively, that the SARS-CoV-2 infection rate will progressively 
increase to 0.5% of the population, it is expected that during the enrollment period 
of this registry 155,000 persons will develop SARS-CoV-2 infection. Considering 
a prevalence of 3% of patients with systemic autoimmune diseases who are 
mostly expected to be chronically treated with immunomodulatory and/or 
immunosuppressive drugs, and 17% with rheumatic diseases without 
immunomodulatory and/or immunosuppressive drugs (28), it is expected that 
around 4,650 and 26,350 patients, respectively, will develop SARS-CoV-2 
infection during the recruitment period. In the event that before December 31, 
2020 the expected numbers are not completed, the registration period will be 
extended until the targeted number is achieved. 
Being mortality the primary outcome and considering that currently the mortality 
rate of COVID 19 in our country is 5.2%, with an expected reduction of 50% for 
those patients taking immunosuppressive drugs, with 80% power and 
alpha=0.05, we would need 796 patients per group. 
RECRUITMENT 
Center selection process and patient recruitment (Figure 1): 
1. All rheumatologists, members of the Argentine Society of Rheumatology 
will be invited to participate in the registry.  
2. The information about this project will be delivered through the usual 
SAR’s information channels: a) NotiSAR (flyers), b) SAR-website (for 
professionals and patients), c) Argentine Journal of Rheumatology, and d) 
Scientific events (National Congress of Rheumatology, Fall Symposium, 
Visiting Professor, and others). 
3. All rheumatologists will have personal interviews with a methodologist 
from the SAR Research Unit to solve doubts and acquire skills for the use 
of the survey, database and different indexes that will be performed. 
4. Enrolment period will take place from July to December 2020. 

 
 
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5. All consecutive patients who meet the inclusion criteria and who have 
signed the informed consent will be included  
6. To guarantee the homogeneity and quality of the information, each 
variable of the registry will have standardized definitions. 
7. The rheumatologist will obtain the information in a face-to-face visit and 
through an exhaustive review of the patient's medical records. This day 
will be defined as baseline visit or index day (T0). 
8. Follow-up visits will be made by the rheumatologist at 12 months. 
VARIABLES AND DEFINITIONS 
Variables and definitions are described in detailed in Appendix 3.  
DATA COLLECTION 
All variables will be collected by self-report, clinical and laboratory examination 
and/or medical records review, performed by the rheumatologist during patient 
hospitalization due to COVID-19, or at the patient control visit performed after 
SARS-CoV-2 infection.  
The data will be entered into the ARTHROS eCRF (online application designed 
ad hoc), which in turn will facilitate generating queries and perform the statistical 
analysis. 
CODING 
Each patient will receive a unique, unchangeable numerical code, even if the 
patient changes locations. If this happens, the rheumatologist in charge will notify 
to the study monitor in order to avoid data duplication. 
QUALITY CONTROL 
A Data Control Committee (DCC) will be created to guarantee quality information 
and to avoid potential data loss. 
To guarantee the quality of the information, the entire process will be monitored 
by a person specifically hired and trained to detect inconsistencies and to 
generate queries to the investigators at each participating center. 
ARTHROS eCRF will have filters that limit the entry of unreliable data (data 
outside the allowed range, etc.). 

 
 
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(A) 1,500 patients with rheumatic diseases treated with immunomodulatory and/or 
immunosuppressive drugs. 
(B) 1,500 patients with rheumatic diseases without treatment with immunomodulatory and/or 
immunosuppressive drugs. 
 
Figure 1. Flow chart showing the information process in the SAR-COVID registry. 
 
PERIODIC REPORTS 
 
Reports will be made at the end of every study visits, including the following 
information: 
• Number of participants.  
• Gender. 
• Diagnoses of the rheumatic diseases. 
• Age at diagnosis of the rheumatic disease.  
• Age at diagnosis of the SARS-CoV-2 infection.  
• Duration of the rheumatic disease at the diagnosis of SARS-CoV-2 
infection. 
• Immunomodulatory and/or immunosuppressive treatments received 
prior to SARS-CoV-2 infection.  
• Immunomodulatory and/or immunosuppressive treatment interruptions 
at SARS-CoV-2 infection. 

 
 
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• COVID-19 clinical and laboratory characteristics. 
• Treatments received for COVID-19.  
• Use of ICU and invasive mechanical ventilation.   
• Mortality. 
These reports will be uploaded to the SAR-COVID website. Other fast 
communication channels could be used if necessary. 
 
STATISTICAL CONSIDERATIONS 
 
Overall comparisons of the general cohort and of both subgroup (patients 
stratified according to be chronically treated or not with immunomodulatory and/or 
immunosuppressive drugs) will be performed using a descriptive statistical 
analysis of sociodemographic, clinical characteristics, laboratory and mortality 
data.  
Continuous variables will be presented as mean and standard deviation when 
distribution is considered normal, or median and interquartile range otherwise. To 
decide whether distribution can be considered as normal the following information 
will be used: boxplot, histogram visual inspection and Shapiro-Wilk test. 
Categorical variables will be summarized as frequencies and percentages.  
To compare associations between treatments used and final result of COVID-19 
infection (recovered or deceased), Chi-square test will be used, and if 
assumptions are not fulfilled, categories will be grouped to apply Fisher exact 
test. 
Two multivariable logistic regression models will be performed, the first to  
evaluate COVID-19 as the outcome variable and the use of immunomodulatory 
and/or immunosuppressive drugs as independent variables adjusting for 
confounding variables; and the second to evaluate the influence of 
sociodemographic conditions and treatment status on the outcomes (admission 
in ICU, use of invasive mechanical ventilation and mortality). 
To compare recovery rate of COVID-19 in patients with rheumatic diseases 
treated chronically or not with immunomodulatory and/or immunosuppressive 
drugs, the Z test will be used to show proportions. 
Nonparametric Wilcoxon signed-rank test for comparison between baseline and 
follow-up visits between the different treatment groups (immunomodulatory 

 
 
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and/or immunosuppressive drugs) and age and sex matched population with 
rheumatic diseases without immunomodulatory and/or immunosuppressive 
drugs for HAQ and EuroQol components.  
All statistical analyses and model development will be performed using R version 
3.6.2. 
 
NAMES AND CONTACT DETAILS  
 
Sociedad Argentina de Reumatología 
 
Unidad de Investigación (Research Unit) 
Contact person: Guillermo J. Pons-Estel. 
Callao 384 Piso 2 Dto 6. 
Ciudad Autónoma de Buenos Aires. 
Tel/Fax: (+54 11) 4371-1759/1643 
E-mail: unisar@reumatologia.org.ar  
 
 
Unidad de Gestión (Management Unit) 
Contact person: Leandro Cino. 
Callao 384 Piso 2 Dto 6. 
Ciudad Autónoma de Buenos Aires. 
Tel/Fax: (+54 11) 4371-1759/1643 
E-mail: gerencia@reumatologia.org.ar  
 

 
 
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TIMETABLE  
 
Milestones 
Duration of the project - From July 2020 to July 2022 
Time  
0 
July 
2020 
December 
2020 
July 
2021 
December 
2021 
July 
2022 
Protocol approval 
 
 
 
 
 
 
Local IRB approval 
 
 
 
 
 
 
Official launch of the project: July, 2020 
 
 
 
 
 
 
Baseline visit (T0) 
 
 
 
 
 
 
Data analysis of T0 visits 
 
 
 
 
 
 
Dissemination of results (T0)* 
 
 
 
 
 
 
Follow-up visit - 12 months (T1) 
 
 
 
 
 
 
Data analysis of all visits from T0-T1  
 
 
 
 
 
 
Dissemination of results* 
 
 
 
 
 
 
*abstracts and manuscript preparation and publication 
 
 

 
 
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Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 
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Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. 
Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington 
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Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and 
epidemiology of 2019 novel coronavirus: implications for virus origins and receptor 
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Furst DE. The risk of infections with biologic therapies for rheumatoid arthritis. 
Seminars in arthritis and rheumatism. 2010;39(5):327-46. 
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Zhai Z, Li C, Chen Y, Gerotziafas G, Zhang Z, Wan J, et al. Prevention and 
Treatment of Venous Thromboembolism Associated with Coronavirus Disease 2019 
Infection: A Consensus Statement before Guidelines. Thromb Haemost. 2020. 
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Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown 
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Deftereos SG, Siasos G, Giannopoulos G, Vrachatis DA, Angelidis C, Giotaki SG, 
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Zhao JP, Hu Y, Du RH, Chen ZS, Jin Y, Zhou M, et al. [Expert consensus on the 
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APPENDIX 1. RHEUMATIC DISEASES.  
 
• ANCA-associated vasculitis (e.g., GPA, EGPA, PAN, MPA)  
• Other vasculitis including Kawasaki disease  
• Antiphospholipid syndrome 
• Autoinflammatory syndrome (including TRAPS, CAPS, FMF, HIDS)  
• Axial spondyloarthritis (including ankylosing spondylitis)  
• Other spondyloarthritis (including reactive arthritis)  
• Behcet's 
• Chondrocalcinosis  
• Chronic recurrent multifocal osteomyelitis  
• Fibromyalgia 
• Giant cell arteritis 
• Gout 
• IgG4-related disease 
• Inflammatory myopathy (e.g. dermatomyositis, polymyositis) 
• Juvenile idiopathic arthritis, not systemic 
• Juvenile idiopathic arthritis, systemic 
• Mixed connective tissue disease 
• Myofascial pain syndrome 
• Ocular inflammation 
• Polymyalgia rheumatica 
• Psoriatic arthritis 
• Rheumatoid arthritis 
• Other inflammatory arthritis 
• Osteoarthritis  
• Osteopenia / Osteoporosis 
• Sarcoidosis 
• Sjogren's syndrome 
• Stills disease, adult onset 
• Systemic lupus erythematosus 
• Systemic sclerosis 
• Undifferentiated connective tissue disease 
 
 
GPA:  Granulomatosis with polyangiitis; EGPA: Eosinophilic granulomatosis 
with polyangiitis; PAN: Polyarteritis nodosa, MPA: Microscopic poyangiitis; 
TRAPS: Tumor necrosis factor receptor-associated periodic syndrome; CAPS: 
Cryopyrin-associated periodic syndrome; FMF: Familial Mediterranean fever; 
HIDS: Hyperimmunoglobulinemia D syndrome.  
 
 
 
 

 
 
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APPENDIX 2. IMMUNOMODULATORY AND/OR IMMUNOSUPPRESSIVE 
CHRONIC TREATMENTS. 
 
Disease-modifying Antirheumatic Drugs (DMARDs) and other Non-Biologics 
treatments.  
• Azathioprine  
• Chloroquine/hydroxychloroquine  
• Cyclosporine 
• Cyclophosphamide 
• Leflunomide 
• Methotrexate 
• Minocycline 
• Mycophenolate mofetil / mycophenolic acid 
• Prednisone 
• Sulfasalazine  
• Tacrolimus 
• Thalidomide 
 
Biologics and small molecules. 
• Actemra (Tocilizumab) 
• Amgevita (Adalimumab) 
• Abrilada (Adalimumab) 
• Benlysta (Belimumab) 
• Cimzia (Certolizumab pegol) 
• Cosentyx (Secukinumab) 
• Enbrel (Etanercept) 
• Enerceptan (Etanercept) 
• Humira (Adalimumab) 
• Ilaris (Canakinumab) 
• Inflectra (Infliximab) 
• Ixifi (Infliximab) 
• Kevzara (Sarilumab) 
• Kineret (Anakinra) 
• Mabthera (Rituximab) 
• Novex (Rituximab) 
• Nucala (Mepolizumab) 
• Ocrelizumab 
• Olumiant (Baricitinib) 
• Orencia (Abatacept) 
• Otezla (Apremilast) 
• Ofev (Nintedanib)  
• Pirfenidona 
• Prolia (Denosumab)  
• Rinvoq (Upadacitinib) 
• Remicade (Infliximab) 
• Remsima (Infliximab)  

 
 
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• Skyrizi (Risankizumab) 
• Simponi (Golimumab) 
• Stelara (Ustekinumab) 
• Taltz (Ixekizumab)  
• Tremfya (Guselkumab) 
• Xeljanz (Tofacitinib) 
 

 
 
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APPENDIX 3. VARIABLES. 
 
All variables will be collected at INDEX DATE by self-report, clinical and laboratory examination and/or medical records review. 
 
I. Socio Demographic Variables 
 
Variable 
Codification 
Physician ID number  
Number 
Unique Patient Identifier 
Number 
Date enrolment 
Number 
City, Province 
Descriptive 
Date of birth 
Number 
Gender 
Male / Female 
Race/ethnicity 
Caucasian / Mestizo / African-Latin American / Other 
Years of formal education  
Number (0-20) 
Medical coverage 
Partial / Full / No 
Socioeconomic status  
Graffar method 
Residence 
Rural / Urban 
 
 
 

 
 
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II. COVID-19 Variables 
 
Variable 
Codification 
COVID-19 Diagnosis: Date 
Number 
COVID-19 Diagnosis: Location 
• Home or standalone  
• Nursing home or assisted living facility 
• Outpatient facility 
• Emergency department 
• Inpatient/hospital 
• Unknown 
• Other 
COVID-19 Diagnosis Method  
• Presumptive diagnosis based on symptoms only 
• PCR 
• Antibody 
• Metagenomic testing 
• CT scan 
• Laboratory assay, type unknown 
• Unknown 
• Other 
Previous symptoms COVID 
Yes / No 
COVID-19: Treatment 
• No treatment except supportive care 
• Remdesivir 
• Lopinavir/ritonavir 
• Antimalarials  
• IL-6 and IL-6r inhibitors  
• IL-1 inhibitors 
• Bevacizumb 
• JAK inhibitors  
• Serpin inhibitors 

 
 
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• Ciclesonide 
• Glucocorticoids 
• Anti-TNF 
• IVIG 
• Plasma from recovered patients 
• Anti-coagulation 
• Other 
Complications 
• No known complications 
• Acute Respiratory Distress Syndrome (ARDS) 
• Macrophagic activation syndrome (MAS) 
• Thrombosis  
• Sepsis 
• Myocarditis or new heart failure 
• Concomitant or secondary infection (e.g. Influenza) 
• Other serious complication 
Infection Acquisition: In the 14 days 
before onset of illness did the patient 
have any of the following? 
• History of travel to an area with documented cases of COVID-19 infection 
• Close contact with a confirmed or probable case of COVID-19 infection 
• Presence in a healthcare facility where COVID-19 infections have been 
managed 
• None of the above (community acquired) 
• Unknown 
• Other 
Abnormal Laboratory test result  
• Anemia: Yes / No / Not assessed 
• D-Dimer abnormal: Yes / No / Not assessed 
• Ferritin > 2000ng/ml: Yes / No / Not assessed 
• IL-6 Levels > UNL: Yes / No / Not assessed 
• sIL2R > UNL: Yes / No / Not assessed 
• Fibrinogen < 250 mg/dL: Yes / No / Not assessed 

 
 
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• Leukopenia (WBC < 5000/mm3) : Yes / No / Not assessed 
• AST or ALT (GOT OR GPT) > UNL: Yes / No / Not assessed 
• Absolut Lymphocyte Count < 1,500/mm3: Yes / No / Not assessed 
• Platelets < 110,000/mm3: Yes / No / Not assessed 
• Triglyceride > 133 mg/dL: Yes / No / Not assessed 
• Known splenomegaly or hepatomegaly: Yes / No / Not assessed 
Pathogen Tests 
• Influenza A: Yes / No / Not assessed 
• Influenza B: Yes / No / Not assessed 
• NON COVID-19 Coronavirus: Yes / No / Not assessed 
• RSV: Yes / No / Not assessed 
• Adenovirus: Yes / No / Not assessed 
• Bacteria: Yes / No / Not assessed 
• Other Respiratory Infection (e.g. fungal): Yes / No / Not assessed 
Develop Interstitial Lung disease 
Yes / No / Unknown 
• Idiopathic pulmonary fibrosis 
• Connective tissue disease, specify CTD:_____________________ 
• Hypersensitivity pneumonitis 
• Sarcoidosis 
• Unknown 
• Other ILD:_____________________________________   
 
•  
 
 

 
 
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III. Rheumatic Disease Variables 
 
Variable 
Codification 
Year rheumatic disease diagnosis 
Number 
Primary rheumatic/autoimmune diagnosis(es) 
• ANCA-associated vasculitis (e.g., GPA, EGPA, PAN, MPA)  
• Other vasculitis including Kawasaki disease  
• Antiphospholipid syndrome 
• Autoinflammatory syndrome (including TRAPS, CAPS, FMF, HIDS)  
• Axial spondyloarthritis (including ankylosing spondylitis)  
• Other spondyloarthritis (including reactive arthritis)  
• Behcet's 
• Chondrocalcinosis  
• Chronic recurrent multifocal osteomyelitis  
• Fibromyalgia 
• Giant cell arteritis 
• Gout 
• IgG4-related disease 
• Inflammatory myopathy (e.g. dermatomyositis, polymyositis) 
• Juvenile idiopathic arthritis, not systemic 
• Juvenile idiopathic arthritis, systemic 
• Mixed connective tissue disease 
• Myofascial pain syndrome 
• Ocular inflammation 
• Polymyalgia rheumatica 
• Psoriatic arthritis 
• Rheumatoid arthritis 
• Other inflammatory arthritis 
• Osteoarthritis  
• Osteopenia / Osteoporosis 

 
 
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• Sarcoidosis 
• Sjogren's syndrome 
• Stills disease, adult onset 
• Systemic lupus erythematosus 
• Systemic sclerosis 
• Undifferentiated connective tissue disease 
Rheumatic disease activity at the time of 
COVID-19 symptom onset or at COVID-19 
diagnosis if 
asymptomatic 
• Remission 
• Minimal or low disease activity 
• Moderate disease activity 
• Severe or high disease activity 
• Unknown 
Physician Global Assessment  
Number 
Patient Global Assessment 
Number 
Glucocorticoids (including prednisone, 
methylprednisolone) at time of COVID-19 
symptom onset (or at COVID-19 
diagnosis if asymptomatic): 
Yes / No / Unknown 
Immune modulating medications immediately 
prior to the time of COVID-19 symptom onset 
(or at COVID-19 diagnosis if asymptomatic): 
Medication 1-5 
Stopped / Continued / Unknown 
Immune modulating medications immediately 
prior to the time of COVID-19 symptom onset 
(or at COVID-19 diagnosis if asymptomatic): 
• None  
• Azathioprine  
• Chloroquine/hydroxychloroquine  
• Cyclosporine 
• Cyclophosphamide 
• Leflunomide 
• Methotrexate 
• Minocycline 

 
 
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• Mycophenolate mofetil / mycophenolic acid 
• Prednisone 
• Sulfasalazine  
• Tacrolimus 
• Thalidomide  
• Actemra (Tocilizumab) 
• Amgevita (Adalimumab) 
• Abrilada (Adalimumab) 
• Benlysta (Belimumab) 
• Cimzia (Certolizumab pegol) 
• Cosentyx (Secukinumab) 
• Enbrel (Etanercept) 
• Enerceptan (Etanercept) 
• Humira (Adalimumab) 
• Ilaris (Canakinumab) 
• Inflectra (Infliximab) 
• Ixifi (Infliximab) 
• Kevzara (Sarilumab) 
• Kineret (Anakinra) 
• Mabthera (Rituximab) 
• Novex (Rituximab) 
• Nucala (Mepolizumab) 
• Ocrelizumab 
• Olumiant (Baricitinib) 
• Orencia (Abatacept) 
• Otezla (Apremilast) 
• Ofev (Nintedanib)  
• Pirfenidona 
• Prolia (Denosumab)  

 
 
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• Rinvoq (Upadacitinib) 
• Remicade (Infliximab) 
• Remsima (Infliximab)  
• Skyrizi (Risankizumab) 
• Simponi (Golimumab) 
• Stelara (Ustekinumab) 
• Taltz (Ixekizumab)  
• Tremfya (Guselkumab) 
• Xeljanz (Tofacitinib) 
At the time of COVID-19 symptom onset (or diagnosis if asymptomatic), was the patient taking any of the following 
medications? 
ACE inhibitor 
Yes and medication continued / Yes and medication stopped / No / Unknown 
Angiotensin receptor blocker 
Yes and medication continued / Yes and medication stopped / No / Unknown 
Nonsteroidal anti-inflammatory (NSAID) 
Yes and medication continued / Yes and medication stopped / No / Unknown 
PD5 inhibitor (e.g., sildenafil) 
Yes and medication continued / Yes and medication stopped / No / Unknown 
Comorbidity and Pregnancy 
• None 
• Interstitial lung disease (e.g. NSIP, UIP, IPF) 
• Obstructive lung disease (COPD/asthma) 
• Other lung disease 
• Diabetes 
• Morbid obesity (BMI 40+) 
• Hypertension 
• Cardiovascular disease (coronary artery disease, congestive heart 
failure) 
• Pulmonary hypertension 
• Chronic renal insufficiency or end stage renal disease 
• Cancer 
• Organ transplant recipient 
• Immunodeficiency  

 
 
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• Inflammatory bowel disease 
• Liver disease 
• Chronic neurological or neuromuscular disease 
• Trisomy 21 
• Psychiatric condition (e.g., schizophrenia, bipolar disorder) 
• Pregnancy 
• Post-partum (< 6 weeks) 
• Unknown 
Smoking Status 
Current smoker / Former smoker / Never smoked / Unknown smoking status 
 
 
IV. Outcome Variables 
 
Variable 
Codification 
Health Assessment Questionnaire (HAQ-DI) 
Questionnaire 
EuroQoL 
Questionnaire 
Global Burden Disease-GBD 
Questionnaire 
Hospitalization  
Yes / No 
Internal medicine hospitalization days 
Number 
UCI hospitalization days 
Number 
Requirement of conventional ventilatory support 
Yes / No 
Conventional ventilatory support days 
Number 
Computed tomography scan 
Yes / No 
Number of computed tomography scan performed 
Number 
Deceased 
Yes / No 
Cause of dead 
Descriptive