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EClinicalMedicine ; 40: 101099, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34490415


Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc.

Infection ; 49(4): 757-762, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33825125


Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

COVID-19/imunologia , Monócitos/imunologia , SARS-CoV-2/fisiologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/sangue , Idoso , Feminino , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/biossíntese , Regulação para Cima
Int J Chron Obstruct Pulmon Dis ; 15: 1325-1334, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606642


Purpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection. Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation. Results: An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure. Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endobronchial valves. Patients with incomplete fissures (left major fissure: FCS <80%; right major fissure: <90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is >95%.

Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Broncoscopia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Países Baixos , Pneumonectomia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Resultado do Tratamento
Exp Ther Med ; 17(2): 1020-1023, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30679968


Psoriasis is one of the most common chronic dermatological conditions, with a strong impact on patients' quality of life. Currently, psoriasis benefits from conventional therapy with a high rate of adverse effects and an increase in non-compliance and self-medication of patients. As such, there is a need to pinpoint low-adverse effects and accessible remedies for this condition. Our single-blind, placebo-controlled study assessed the effect of sea buckthorn extract on psoriasis lesions in previously untreated patients. Our results showed an improvement in Psoriasis Area Severity Index (PASI) scores and in Dermatology Life Quality Index (DLQI) scores when compared to the baseline values, as well as at the 4- and 8-week time marks for the lesions treated with sea buckthorn extract. By contrast, the measurements for the placebo treated lesions showed no alteration at the 4-week mark, and significant worsening at the end of the trial. These findings provide a solid, optimistic base for the in-depth research of sea buckthorn as an adjuvant or a component in psoriasis care protocols.