ABSTRACT
OBJECTIVE: To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS-CoV-2 vaccine (Sinovac-CoronaVac) and the influence of different medications in SLE. Safety was also assessed. METHODS: We conducted a prospective controlled study of 232 SARS-CoV-2-naive SLE patients and 58 SARS-CoV-2-naive controls who were vaccinated with 2 doses of Sinovac-CoronaVac with a 28-day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed. RESULTS: Patients and controls were well balanced for age (P = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P < 0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108-0.427], P < 0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107-0.378], P < 0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC (P = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC (P < 0.001) and NAb positivity (P < 0.001). Safety analysis revealed no moderate/severe adverse events. CONCLUSION: Sinovac-CoronaVac has a moderate immunogenicity in SARS-CoV-2-naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine-booster dose (ClinicalTrials.gov identifier: NCT04754698).
Subject(s)
COVID-19 Vaccines , Lupus Erythematosus, Systemic , Antibodies, Viral/therapeutic use , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Lupus Erythematosus, Systemic/immunology , Prospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
ABSTRACT
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has progressed rapidly around the world, reaching a lethality of up to 20% due to acute respiratory distress syndrome (ARDS). This latter condition is a relevant concern for systemic lupus erythematosus (SLE); however, data on this topic are limited to few case series. Our objective was to evaluate in hospitalized patients with SLE and with COVID-19-associated ARDS (confirmed by reverse transcription-polymerase chain reaction) the risk of mortality and combined poor outcomes (death, intensive care unit [ICU] admission, and/or mechanical ventilation [MV] use) and to compare with that of patients without SLE. METHODS: This is a nationwide cross-sectional study of patients with severe acute respiratory syndrome coronavirus 2 nested in the national Influenza Epidemiological Surveillance Information System (Sistema de Informação de Vigilância Epidemiológica da Gripe [SIVEP-gripe]). Mortality rates, frequencies of ICU admissions, and MV use for 319 patients with SLE and 251 800 patients without SLE were calculated as well as relative risks (RRs). A fully adjusted multiple logistic regression was performed to adjust factors, such as age and well-known comorbidities, that might impact worse outcomes. RESULTS: Patients with SLE had an increased risk of death and combined poor outcome compared with patients without SLE (RR = 1.738, 95% confidence interval [CI]: 1.557-1.914, and RR = 1.391, 95% CI: 1.282-1.492, respectively). Among all investigated comorbidities, SLE yielded the higher risk of death and combined poor outcomes (RR = 2.205, 95% CI: 1.780-2.633, and RR = 1.654, 95% CI: 1.410-1.88, respectively). CONCLUSIONS: This study provides novel evidence that patients with SLE hospitalized because of COVID-19 have significantly higher risks of death and poor outcomes compared with patients without comorbidities and patients with other comorbidities.
ABSTRACT
BACKGROUND: Brazil is a country with a high burden of tuberculosis (TB). The immunomodulatory effect of biological therapies is associated with an increased risk of infection. This study evaluated the frequency of TB infection in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA) after the use of biologic agents in a single center of rheumatology. METHODS: In this observational study, 161 consecutive adult patients with RA, JIA, AS, and PsA using biological therapy were followed up during 55 months to evaluate the occurrence of TB infection throughout treatment. All patients were screened for latent TB infection (LTBI), and TB disease was excluded before introduction of biological therapy. Patients with LTBI received prophylaxis with isoniazid before the start of biological treatment. RESULTS: Of 161 patients on biologics, 31 (19.25%) had positive tuberculin skin test (TST) and received LTBI treatment. Eleven (6.8%) cases of TB were detected in patients on biologics, six (54.5%) had AS, one had PsA (9.09%), two had RA (18.18%), and two had JIA (18.18%). Regarding the use of different biologics, six (54.5%) patients received adalimumab, three (27.2%) infliximab, one (9.09%) etanercept, and one (9.09%) tocilizumab. CONCLUSION: In this study, the frequency of TB infection among 161 patients on biologics, during 55 months of follow-up, was 6.8%. Compared with the national registry of patients receiving biologics (BiobadaBrasil - January 01, 2009 to May 31, 2013), a higher incidence of TB (6.8 versus 0.44%) was found in this sample of patients receiving biological therapy. This study highlights that in a country with high TB burden, the possibility of TB infection in a patient receiving biological therapy should always be considered, even after prophylaxis with isoniazid.
ABSTRACT
AIM: To assess drug switching, rates of remission and disease activity in Brazilian patients with rheumatoid arthritis (RA) treated with biologic agents. MATERIALS & METHODS: Using a retrospective method, a total of 94 adult patients were included. RESULTS: Anti-TNF was the first choice therapy in 85 (90.4%) patients. After an average of 8 years of follow-up, 55 (59%) patients were taking anti-TNF, 18 (19%) abatacept, eight (9%) tocilizumab and 13 (14%) rituximab. In this period, 99 switches of biological therapy were registered in 55 patients. CONCLUSION: After 8 years of follow-up, 54% of the RA patients on biological therapy were still experiencing high or moderate activity despite established treatment, including switching between different biologic agents.
