ABSTRACT
Background: Several trials have reported lower seroconversion rates in patients with autoimmune rheumatic diseases than in healthy patients. In Argentina, the vaccines that were available during the development of this study were: Sputnik V (Gam-COVID-Vac), AstraZeneca (ChAdOx1 nCov-19), Sinopharm (BBIBP-CorV) and Moderna (mRNA-1273). Limited information is available about vaccines against SARS-CoV2 with inactivated virus or viral vector in autoimmune patients. Objectives: To evaluate the humoral immune response to vaccines against SARS-CoV2 in patients with autoimmune rheumatic diseases;to compare the humoral response among patients with Systemic Lupus Erythematosus (SLE) and other autoimmune diseases and to analyse the variables associated. Methods: We included patients with autoimmune rheumatic diseases (Rheumatology Unit of Padilla Hospital, Tucumán, Argentina), who received vaccination against SARS-CoV2 from June 2021. Sociodemographic, comorbidities, related to rheumatic disease, vaccination and SARS-CoV2 infection were the variables recorded. To evaluate the humoral immune response, the neutralizing anti-S-RBD IgG antibody titres were determined by ELISA 'In House' test with a cut-off titre of 200 (IMMCA). The times established for the serological determinations were: T0 or baseline: 1st vaccine dose, T1: 14 ± 2 days after the 1st dose, T2: 2nd dose, T3: 21-45 days after the 2nd dose, T4: 30 days after the 3rd dose, T5: 6 months and T6: 12 months after the 3rd dose. Results: 66 patients were included, 91% women and 92.4% Amerindians. The mean age was 40.7 ± 11.4 years;53% with SLE, 15.2% Rheumatoid Arthritis, 7.6% Systemic Sclerosis, 7.6% Juvenile Idiopathic Arthritis, 7.6% Systemic Vasculitis and 9% other diagnoses;mean disease duration was 12.05 ± 7. 5 years;63.6% had at least one comorbidity (57% HBP, 31% overweight or obesity). At baseline, the treatments received were: corticoster-oids (37.9%, prednisone mean dose 4.12 ± 8 mg/day), cDMARDs (75.7%), bDMARDs (18.2%): Rituximab (58.3%) and anti TNF (25%). Sixteen patients (24.2%) had previous COVID19 (75% mild symptoms). The vaccines applied were: AstraZeneca 38.2%, Sinopharm 31.7%, Sputnik V 19%, and combined schedule Sputnik V/Moderna in 11%. At baseline, 28.8% had detectable anti-S-RBD IgG antibodies. This frequency increased to 48.4% at 1st dose and 70.2% at 2nd dose. The variables that were associated with lower sero-conversion rates and lower antibody titre were vaccination with Sinopharm (p 0.028) and treatment with bDMARDs (p 0.02), none of the 5 patients with Rituximab showed seroconversion. There were no significant differences in the levels of anti-S-RBD IgG antibodies between patients with SLE and the other rheumatic diseases. Patients who had SARS-CoV2 infection prior to vaccination had higher antibody titres in both T1 (p 0.006) and T2 (p 0.002) but after the two doses this difference was not significant (p 0.67). In the regression analysis, the variables that were independently associated with seroconversion were the type of vaccine applied at the 1st dose and the hypertensive disease. The chance of responding to vaccination was 13 and 9 times higher for those who received Sputnik V (OR 12.78;95% CI 1.46-315.9) or AstraZeneca (OR 8.61;95% CI 1.63-72.5) respectively, than Sinopharm in the 1st dose. The chance of being a responder was 88% lower for hypertensive patients (OR 0.12;95% CI 0.02-0.58). Conclusion: In this preliminary analysis, a seroconversion rate of 70.2% was associated with two-dose vaccination for SARS-CoV2 in patients with autoimmune rheumatic diseases. There were no differences in the serological response between patients with SLE and other rheumatic diseases. The humoral immune response was lower in patients with bDMARDs and null in those who received Rituximab. Seroconversion and antibody titres levels were associated with the type of vaccine applied, being Sinopharm who presented the lowest response. The follow-up will provide more knowledge about the behaviour of the humoral response in our patients.
ABSTRACT
Background: High disease activity, treatment with glucocorticoids (GC) and rituximab (RTX), have been related to worse outcomes of COVID-19. Objectives: To assess the clinical characteristics and severity of the SARS-CoV-2 infection in patients with rheumatoid arthritis (RA) included in the SAR-COVID registry and to identify factors associated with poor outcomes. Methods: SAR-COVID is a national, longitudinal and observational registry. Patients of ≥18 years old, with diagnosis of RA (ACR-EULAR criteria 2010) who had confrmed SARS-CoV-2 infection (RT-PCR or positive serology) were included between 13-8-20 and 31-7-21. Sociodemographic and clinical data, comorbidities, disease activity and treatment at the moment of the SARS-CoV-2 infection were collected. Additionally, infection symptoms, complications, medical interventions and treatments for COVID-19 were registered. Infection severity was assessed using the WHO-ordinal scale (WHO-OS)1. A cut-off value of ≥5 identifed patients with severe COVID-19 and those who died. Statistical analysis: Descriptive statistics. Chi2 or Fischer test, Student T test or Mann-Whitney and Kruskal Wallis or ANOVA, as appropriate. Multiple logistic regression model. Results: A total of 801 patients were included, with a mean age of 53.1 ± 12.9 years, most of them were female (84.5%) and the median (m) disease duration was 8 years (IQR 4-14). One third were in remission and 46.4% had comor-bidities, being the most frequent, hypertension (26.9 %), dyslipidemia (13.5 %), obesity (13.4 %) and diabetes (8.9%). Moreover, 3.2% had interstitial lung disease (ILD) associated with RA. At SARS-CoV-2 diagnosis, 42.5% were receiving glucocorticoids (GC), 73.9% conventional (c) disease modifying antirheumatic drugs (DMARD), 24% biologic (b) DMARD and 9.1% targeted synthetic (ts) DMARD. Among bDMARD, the most frequently used were TNF inhibitors (17%), followed by abatacept (2.8%), IL-6 inhibitors (2.4%) and rituximab (RTX) (2.1%). During the SARS-CoV-2 infection, 95.8% had symptoms, 27% required hospital-ization, 7.9% presented complications and 4.4% died due to COVID-19. Severe disease and death (WHO-OS≥5) was present in 7.5% of the patients. They were older (62.9±12.5 vs 52.2±12.7, p<0.001), and they had more frequently ILD (18.5% vs 2%, p<0.001), comorbidities (82.5% vs 43.7%, p<0.001), ≥2 comor-bidities (60.3% vs 25.8%, p<0.001), treatment with GC (61% vs 40.7%, p=0.04) and RTX (8.3% vs 1.6%, p=0.007). Conversely, the use of cDMARD and TNF inhibitors was more frequent in patients with WHO-OS<5, nevertheless this difference was not signifcant. Disease activity was comparable between groups. In multivariable analysis, older age, the presence of diabetes, ILD, the use of GC and RTX were signifcantly associated with WHO-OS≥5 (Figure 1). Furthermore, older age (65.7±10.8 vs 52.4±12.8, p<0.001), the presence of comor-bidities (87.9% vs 44.7%, p<0.001), chronic obstructive pulmonary disease (21.9% vs 5.2%, p=0.002), diabetes (30.3% vs 7.9%, p<0.001), hypertension (57.6% vs 25.6%, p<0.001), cardiovascular disease (15.6% vs 3.2%, p=0.005), cancer (9.1% vs 1.3%, p=0.001), ILD (23.3% vs 2.4%, p<0.001) and the use of GC (61.8% vs 41.4%, p=0.02) were associated with mortality. Older age [OR 1.1 IC95% 1.06-1.13] and the use of GC 5-10 mg/day [OR 4.6 IC95% 1.8-11.6] remained signifcantly associated with death due to COVID-19. Conclusion: Treatment with RTX and GC, as well as older age, the presence of diabetes and ILD were associated with poor COVID-19 outcomes in this national cohort of patients with RA. Older patients and those taking GC had a higher mortality rate.
ABSTRACT
Background: SARS CoV-2 infection has recently burst onto the global scene, and the knowledge of the course of this infection in patients with rheumatic diseases receiving immunomodulatory treatment is still insufficient. The Argentine Society of Rheumatology (SAR) designed a national registry called SAR-COVID in order to get to assess our reality. Objectives: To identify the particular characteristics of patients with rheumatic diseases and COVID-19 in Argentina (SAR-COVID Registry), and to compare them with the data reported at the Latin American and Global level (Global International Alliance Rheum-COVID Registry). Methods: A national, multicenter, prospective and observational registry was carried out. Patients older than 18 years, with a diagnosis of rheumatic disease and SARS-CoV-2 infection by PCR or serology, were included between August 13, 2020 and January 17, 2021. Demographic data, underlying rheumatic disease (activity of the disease, current treatment), comorbidities, clinical-laboratory characteristics of the SARS-CoV-2 infection, as well as received treatments (pharmacological, oxygen therapy / ventilatory support) and outcomes (hospitalization, mortality) were recorded. The characteristics of the included patients were compared with the data reported at the Latin American and global level. Descriptive statistics were performed. Comparisons between groups were made using ANOVA, chi2 or Fisher's test, according to the type of variable. Results: Four hundred sixty-five patients from Argentina, 74 patients from Latin America and 583 from the rest of the world were included, mostly women (79.6%, 73% and 71% respectively), with a mean age of 50.2 (SD 15.3), 53.5 (DE 15.6) and 55.8 (15.5), years respectively. The most frequent rheumatic diseases in the three groups were rheumatoid arthritis (43.9%, 35%, and 39%) and systemic lupus erythematosus (16.1%, 22%, and 14%) (Table 1). In Argentina, fewer patients received specific pharmacological treatment for COVID-19 (40.9%, 68% and 43% respectively, p <0.0001), and there was a lower requirement of NIMV / IMV (Non-Invasive Mechanical Ventilation/Invasive Mechanical Ventilation) than in the rest of Latin America and the world (10.5% vs 31% vs 13%, p <0.0001). Hospitalization was lower in Argentina than in the rest of Latin America (37.4% vs 61% p 0.0002) and of the world (37.4% vs 45% p 0.0123), and mortality was numerically lower in Argentina, but without statistically significant differences between the three groups (6.9%, 12% and 11%;p 0.6311). Most of the patients, (86.9%) did not present any complications in Argentina, with a statistically significant difference with the rest of the groups (62% and 77%, p <0.0001) (Graph 1). Conclusion: The patients with rheumatic diseases and SARS-CoV-2 infection reported in this argentinian registry received less specific pharmacological treatment for COVID-19, presented fewer complications and required less ventilatory support, than those reported in the Latinoamerican and Global registry. However, no statistically significant differences were observed in terms of mortality.