摘要：This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19). A total of 310 patients diagnosed with COVID-19 were studied. A comparison was made between two groups of patients, those with hypertension and those without hypertension. Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed. A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients ( P < 0.05). However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity. COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease. Patients with hypertension should be given additional attention to prevent worsening of their condition.
摘要：Introduction : Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and informs public health interventions. Methods : We conducted a comprehensive study linking germline genetic variation and gene expression with antibody response to 28 antigens for 16 viruses using serological data from 7924 participants in the UK Biobank cohort. Using test results from 2010 UK Biobank subjects, we also investigated genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results : Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. Genome-wide association analyses discovered 7 novel genetic loci associated with viral antibody response (P<5.0×10 -8 ), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for Merkel cell polyomavirus (MCV), as well as CXCR5 (11q23.3) and TBKBP1 (17q21.32) for human herpesvirus 7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including ECSCR : P=5.0×10 -15 (MCV), NTN5 : P=1.1×10 -9 (BKV), and P2RY13 : P=1.1×10 -8 (Epstein-Barr virus nuclear antigen). We also demonstrated pleiotropy between viral response genes and complex diseases, such as C4A expression in varicella zoster virus and schizophrenia. Finally, our analyses of SARS-CoV-2 revealed the first genome-wide significant infection susceptibility signal in EHF , an epithelial-specific transcriptional repressor implicated in airway disease. Targeted analyses of expression quantitative trait loci suggest a possible role for tissue-specific ACE2 expression in modifying SARS-CoV-2 susceptibility. Conclusions : Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants of host-virus interaction. Our results may have implications for complex disease etiology and COVID-19.
作者：Linda Kachuri,Stephen S Francis,Maike Morrison,Yohan Bossé,Taylor B Cavazos,Sara R Rashkin,Elad Ziv,John S Witte
摘要：Background Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. Methods A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. Results The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. Conclusions A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.
