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ObjectivesOur aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination. MethodsIn this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-{gamma} release assay after the second dose. ResultsBNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response ({beta}=-78; p=0.007, {beta}=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naive B cell frequencies ({beta}=2; p=0.018, {beta}=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. ConclusionMMF, MTX and poor baseline humoral immune status, particularly: low naive B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up. KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIBNT162b2 efficacy and safety has been described in studies mixing different RMDs C_LI What does this study add?O_LINo serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients. C_LIO_LINot only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody response C_LIO_LIAlbeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders. C_LI How might this impact on clinical practice or future developments?O_LIThese parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine. C_LI
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SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-{kappa}B activity, TNF- signaling, associated with decreased gene expression of NF-{kappa}B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1 and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.
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It is currently unknown whether acquired immunity to common alpha- and beta-coronaviruses provides cross-protection against SARS-CoV-2. In this study, we found that certain patient sera and intravenous immunoglobulins (IVIG) collected prior to the COVID-19 outbreak were cross-reactive to SARS-CoV-2 full-length Spike, S2 domain, and Nucleocapsid. However, their presence did not translate into neutralizing activity against SARS-CoV-2 in vitro. Importantly, we detected serum IgG reactivity to common coronaviruses in the early sera of patients with severe COVID-19 before the appearance of anti-SARS-CoV-2 antibodies. Collectively, the results of our study indicate that pre-existing immunity to common coronaviruses does not confer cross-protection against SARS-CoV-2 in vivo.
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BackgroundIdentification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial. ObjectiveTo evaluate the rate of daily smokers in patients with COVID-19. MethodsCOVID-19 in-and outpatients from a large French university hospital were systematically interviewed for their smoking status, use of e-cigarette and nicotinic substitutes. The rates of daily smokers in in-and outpatients were compared to those in the 2019 French general population, after standardization for sex and age. ResultsThe inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%) and 137 women (40.3%), median age for both 66 years, with a daily smokers rate of 4.1 % CI95% [2.3-6.9] (5.4% of men, 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years), and 77 women (55.4%, median age 44 years). The daily smoker rate was 6.1 % CI 95% [2.7 - 11.6] (5.1% of men, 6.8% of women). In the 2019 French population, the daily smoker rate was 24.0% (27.5% of men, 20.7% of women). Among inpatients, daily smokers represented 2.2% and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients. ConclusionDaily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population
