Characteristics associated with Covid-19 in patients with Rheumatic Disease in Latin America
https://doi.org/10.46856/grp.10.e003
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Ugarte-Gil MF, Marques CDL, Alpizar-Rodriguez D, Pons-Estel GJ, Xibille-Friedmann D, Paiva E, et al.. Characteristics associated with Covid-19 in patients with Rheumatic Disease in Latin America: data from the Covid-19 Global Rheumatology Alliance physician-reported registry [Internet]. Global Rheumatology. Vol. 1 / Jun - Dic [2020]. Available from: https://doi.org/10.46856/grp.10.e003
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Table 1: Demographic and clinical characteristics of patients with rheumatic disease with COVID-19
Figure 1: Rate of non-invasive or invasive ventilation support, hospitalization and death among patients from Latin America and Rest of the World
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Characteristics associated with Covid-19 in patients with Rheumatic Disease in Latin America
Objective: To compare the characteristics of patients with rheumatic diseases and COVID-19 reported in Latin America with those from the rest of the world.
Methods: Patients from the COVID-19 Global Rheumatology Alliance Physician-Reported Registry were included. Demographic data, rheumatic disease characteristics, comorbidities, COVID-19 diagnosis and treatment, as well as outcomes, were analyzed. Chi-square and Student’s t-tests were used to compare groups (Latin America vs. the rest of the world). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization (yes/no) and ventilatory support (non-hospitalized or supplemental oxygen only vs. non-invasive, invasive ventilation, or ECMO). Poisson regression models were used to estimate ORs and 95% CIs for mortality.
Results: Seventy-four patients from Latin America and 583 from the rest of the world were included. The most common rheumatic diseases in both groups were rheumatoid arthritis (35% vs. 39%) and systemic lupus erythematosus (22% vs. 14%). Mortality was similar between groups (12% in Latin America vs. 11% in the rest of the world; p = 0.88). However, patients from Latin America were more likely to require non-invasive or invasive ventilation after adjustment [OR = 2.29, 95% CI (1.29–4.07); p < 0.01].
Conclusion: Patients from Latin America with rheumatic diseases and COVID-19 reported to this global registry had a higher need for ventilatory support, although mortality was comparable to that of patients from the rest of the world.
The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 17, more than 8.3 million people had been diagnosed with COVID-19, and over 440,000 patients had died. The pandemic began in Wuhan, China, in late 2019; the epicenter then shifted to Europe, followed by the United States, and is now moving through Latin America. Within Latin America, Brazil is the most affected country in the region (and the second worldwide), with over 950,000 cases and more than 46,000 deaths, followed by Peru with over 240,000 cases and more than 7,200 deaths, Chile with over 220,000 cases and more than 3,600 deaths, and Mexico with nearly 160,000 cases and more than 19,000 deaths (1).
Socioeconomic factors will undoubtedly make the impact of COVID-19 more severe in this region than in the developed world. Latin America is one of the regions with the highest levels of inequality in access to healthcare services (2). Latin American countries have lower human development indexes, less access to clean water, and greater distrust in public institutions compared to the 15 non-Chinese countries with the highest number of reported COVID-19 cases as of March 8, 2020 (mainly the United States and Europe) (3). Additionally, due to precarious housing conditions in many areas, social distancing is practically impossible for a large portion of the Latin American population. The COVID-19 pandemic has overwhelmed the healthcare systems in Latin America, with an insufficient number of hospital beds, intensive care units, and healthcare workers (4). Furthermore, comorbidities associated with poor COVID-19 outcomes—such as obesity, diabetes, and hypertension—are highly prevalent in the region and may contribute to worse clinical outcomes (5).
The impact of autoimmune diseases and immunosuppressive medications on the risk of infection and prognosis of COVID-19 has not yet been clearly defined. However, autoimmune diseases and immunosuppressive treatments are known to increase the risk of serious infections; therefore, these patients could be at greater risk for worse outcomes compared to the general population (6, 7). In addition, patients with rheumatic diseases may also suffer from cardiovascular, pulmonary, and renal diseases, placing them at greater risk for COVID-19–related complications (8–11). People with rheumatic diseases in Latin America may be at a particular disadvantage compared to those in developed countries, especially regarding access to regular healthcare and appropriate treatments before the pandemic—challenges that are further exacerbated during the COVID-19 crisis (12).
To determine the impact of SARS-CoV-2 infection on individuals with rheumatic diseases and to evaluate the effect of immunosuppressive medications on clinical outcomes, the COVID-19 Global Rheumatology Alliance (C19-GRA) was established. Among its efforts, the Alliance developed a physician-reported registry that includes adult patients from around the world (13, 14). Latin American countries are actively participating in this global effort. The purpose of this study is to compare the characteristics of Latin American patients in the C19-GRA physician registry with those of patients from the rest of the world.
The details of this registry have been described previously (15, 16). In summary, data from the C19-GRA on patients diagnosed with rheumatic diseases and COVID-19 are collected by rheumatologists and other healthcare professionals through two parallel international portals for data entry: one limited to European countries (hosted by the University of Manchester, UK) and the other for all other countries (hosted by the University of California, San Francisco, USA). The database has been reviewed by ethics committees in several countries. Using the UK Health Research Authority’s decision tool, it was determined that the EULAR-COVID-19 database does not qualify as a research study and does not require ethical approval from the UK National Health Service (NHS). The Institutional Review Board (IRB) of the University of California, San Francisco reviewed the COVID-19 Global Rheumatology Alliance registry and determined that it does not constitute human subjects research, as it is intended for surveillance or quality improvement. In Latin America, the protocol has been reviewed and approved according to local regulations. Patients from Argentina, Brazil, Chile, Colombia, the Dominican Republic, Ecuador, Honduras, Mexico, and Peru were included. Patient consent is not required. The data collection form is available in multiple languages, including English, Spanish, Portuguese, among others.
Rheumatologists report how the COVID-19 diagnosis was made, including PCR testing, serologic or metagenomic tests, CT scans, or other laboratory studies; a presumptive diagnosis based on specific symptoms, signs, or imaging findings is also accepted. Sociodemographic information was recorded, including age, sex, race/ethnicity (reported by the physician, and in most cases derived from patient self-report in the medical record), smoking status, rheumatic disease diagnosis, disease activity (as assessed globally by the physician), comorbidities, and medications used prior to COVID-19 diagnosis.
Medications used before COVID-19 infection were categorized as: conventional synthetic DMARDs (csDMARDs; including antimalarials such as hydroxychloroquine and chloroquine; azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, tacrolimus); biologic DMARDs (bDMARDs; abatacept, belimumab, CD20 inhibitors, IL-1, IL-6, IL-12/23, IL-17 inhibitors, and tumor necrosis factor [TNF] inhibitors); and targeted synthetic DMARDs (tsDMARDs), specifically Janus kinase (JAK) inhibitors and glucocorticoids.
In addition, data were collected on whether patients had received pharmacological treatment for COVID-19, the status of the infection (resolved, unresolved, unknown), need for ventilatory support [not required, supplemental oxygen, non-invasive ventilation, invasive ventilation/extracorporeal membrane oxygenation (ECMO), required but type unknown], and outcomes [death, hospitalization, complications such as ARDS, sepsis, myocarditis/heart failure, secondary infections, cytokine storm].
Statistical Analysis
Data are reported as means and standard deviations (SD), or as numbers and percentages. The characteristics of Latin American patients were compared with those from the rest of the world using the chi-square test or Student’s t-test. To assess whether being from Latin America was associated with worse outcomes, multivariable regression models were used. For mortality, a Poisson regression model was applied; for hospitalization (yes/no) and need for ventilatory support (non-invasive or invasive ventilation vs. none), logistic regression models were used.
All models were adjusted for: sex, age over 65 years, smoking status (ever/never), rheumatic disease diagnosis [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis, spondyloarthritis, or other], comorbidities (hypertension/cardiovascular disease, pulmonary disease, diabetes, and chronic kidney disease/ESRD), pre-infection rheumatologic medications (csDMARDs monotherapy; bDMARDs/tsDMARDs; combination therapy csDMARDs + bDMARDs/tsDMARDs), NSAID use, glucocorticoid use (prednisone or equivalent), and disease activity (remission/low vs. moderate/high).
All analyses were performed using Stata version 16.0 (StataCorp, Texas, USA).
From March 24 to May 22, 2020, data were collected from 74 patients in Latin America; data from patients in the rest of the world collected up to April 20, 2020, were used for comparison (n = 583).
The characteristics of both groups are presented in Table 1. Rheumatoid arthritis (RA) (35% and 39%, respectively) and systemic lupus erythematosus (SLE) (22% vs. 14%, respectively) were the most common diagnoses in both groups. Psoriatic arthritis was less frequent among patients reported by providers in Latin America compared to those from other countries (3% vs. 13%, p = 0.02).
Latin American patients more frequently used conventional DMARDs (81% vs. 66%, p = 0.01), antimalarials (38% vs. 21%, p < 0.01), and glucocorticoids (51% vs. 31%, p < 0.01) than patients from other countries, but used biologic DMARDs less frequently (16% vs. 35%, p < 0.01). Pharmacologic treatment for COVID-19 (68% vs. 43%, p < 0.01), as well as for acute respiratory distress syndrome (ARDS) (30% vs. 9%, p < 0.01), was more common among patients in Latin America. Mortality was similar between the groups (12% vs. 11%, p = 0.88), but hospitalization was more frequent in Latin American patients (61% vs. 45%, p = 0.02).
In multivariable analyses, after adjusting for previously described covariates, cases reported by providers in Latin America were associated with a greater need for non-invasive or invasive ventilatory support [OR = 2.29; 95% CI (1.29, 4.07), p < 0.01], but not with a higher likelihood of death [OR = 1.34; 95% CI (0.65, 2.78), p = 0.43] or hospitalization [OR = 1.79; 95% CI (0.99, 3.20), p = 0.05].
Although Latin American patients with rheumatic diseases reported to the COVID-19 Global Rheumatology Alliance (C19-GRA) registry had higher rates of acute respiratory distress syndrome (ARDS) and used glucocorticoids more frequently and at higher doses, their mortality rate was similar to that of patients from the rest of the world.
Poverty and access to healthcare services influence the risk of contracting COVID-19. In New York, the infection rate was 1,746.84 per 100,000 people in poor neighborhoods, compared to 2,600.46 per 100,000 in wealthy neighborhoods. The role of social determinants of health is even more notable in terms of prognosis: the risk of death was more than twice as high in areas of very high poverty compared to areas of low poverty (242.3 vs. 104.88 per 100,000 people) (17). Based on observations from other countries, it could be assumed that the pandemic would hit Latin America particularly hard. Indeed, as of May 22, Chile had 3,012 confirmed cases per million people, Mexico 462/1,000,000, Peru 3,299/1,000,000, and Brazil 1,459/1,000,000, compared to the U.S. (4,765/1,000,000), Russia (2,176/1,000,000), or France (2,209/1,000,000). The high number of cases in Latin America occurred despite the fact that the epidemic began later in the region (18). COVID-19 mortality in Latin America ranged from 1.02% (Chile) to 10.9% (Mexico); however, it is important to note that these rates depend on the number of tests performed, which varies greatly between countries (18). In Latin America, fewer than 10 out of 20 countries have more than 2.5 physicians and nurses per 1,000 people. For example, Guatemala has 0.4 physicians per 1,000 people, Nicaragua 1.0/1,000, Peru 1.3/1,000, Paraguay 1.4/1,000, Bolivia, the Dominican Republic, and El Salvador 1.6/1,000, Ecuador 2.0/1,000, and Brazil and Colombia 2.2/1,000; whereas the United States and Canada have 2.6/1,000 people. Moreover, healthcare personnel in Latin America are concentrated in major cities, and only Costa Rica, Cuba, and Uruguay invest more than 6% of their gross domestic product in health (3.4). The lower frequency of biologic DMARD use among patients reported to the registry likely reflects limited access to healthcare services and specialized medications in Latin America. Additionally, in a recent report that included six systemic autoimmune diseases (SLE, systemic sclerosis, idiopathic inflammatory myopathies, Sjögren’s syndrome, mixed connective tissue disease, and ANCA-associated vasculitis), the age-standardized mortality rate was lower in Europe than in other regions, including Latin America, with the largest difference observed in patients with SLE; in this group, Latin American patients had a fivefold higher age-standardized mortality rate compared to Europeans. However, it remains unclear whether this difference is due to genetic, environmental, healthcare system–related, social determinants of health, or a combination of all these factors (19). Altogether, one would expect the mortality rate to be higher in this region than in the rest of the world, but current data do not support this assumption.
At present, it is difficult to determine whether the higher frequency of complications (such as ARDS or the need for ventilatory support) in the Latin American population is due to sociodemographic characteristics, weaknesses in the healthcare systems, or other factors such as adverse events from treatments used for COVID-19, the severity of underlying disease (as suggested by the more frequent use of conventional DMARDs), or immunogenetic factors. Another contributing factor may be the use of higher doses of prednisone, which has been identified as a predictor of hospitalization in the C19-GRA registry, or the lower use of anti-TNF therapies, which have been reported as protective against hospitalization in the same registry (16), or even adverse events related to COVID-19 treatments.
One of the strengths of this study is that it includes the largest registry of patients with rheumatic diseases and COVID-19. The C19-GRA registry includes cases from around the world. Additionally, this study highlights the importance of examining the impact of COVID-19 on the daily lives of patients with rheumatic diseases.
However, this study also has several limitations. First, being a voluntary registry, it does not capture all cases of COVID-19 in patients with rheumatic diseases. Second, the relatively small number of reported cases in Latin America and the lack of widespread testing strategies in most countries of the region hinder the identification of all cases, which may lead to selection bias and limits the ability to conduct more detailed multivariable analyses. As more cases from Latin America are reported, we hope to conduct country-level comparisons in future analyses. Third, since not all countries have contributed patients to the registry, there may be some reporting bias. Nevertheless, it is important to note that the countries with the highest number of COVID-19 cases have contributed patients to the registry. Fourth, since hospitalization criteria vary between countries due to multiple factors, such as hospitalization policies, bed availability, and case burden, not all hospitalizations likely reflect the same level of disease severity.
This communication should reinforce the importance of reporting COVID-19 cases in people with rheumatic diseases in Latin America and around the world, in order to generate evidence that can ideally be translated into better recommendations and treatments for our patients.
The authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
The authors received no financial support for the research, authorship, and/or publication of this article.
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