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BackgroundUnderstanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown. MethodsWe constructed a powerful computational framework to characterize the host genetics-influenced immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets (N = 606,534 cells). ResultsWe found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly-expressed genetics-risk genes increased with the severity of COVID-19. Three cell-subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were specifically expressed in these three cell types, respectively. CCR1+CD16+monocytes and ABO+ megakaryocytes with significant up-regulated genes including S100A12, S100A8, S100A9, and IFITM1 confer higher risk to the cytokine storms among severe patients. CXCR6+ memory CD8+ T cells exhibit a notable polyfunctionality of multiple immunologic features, including elevation of proliferation, migration, and chemotaxis. Moreover, we observed a prominent increase in cell-cell interactions of both CCR1+ CD16+monocytes and CXCR6+ memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues, and elevated interactions with epithelial cells could contribute to enhance the resident to lung airway for against COVID-19 infection. ConclusionsWe uncover a major genetics-modulated immunological shift between mild and severe infection, including an increase in up-regulated genetic-risk genes, excessive secreted inflammatory cytokines, and functional immune cell subsets contributing high risk to severity, which provides novel insights in parsing the host genetics-influenced immune cells for severe COVID-19.
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Objective:To investigate the clinical characteristics of elderly patients with coronavirus disease 2019(COVID-19), in order to provide scientific evidence for the diagnosis and treatment of COVID-19 in elderly patients.Methods:Clinical data of 102 patients with COVID-19 admitted to the B11 East Ward of the Zhongfaxincheng campus and the E1-3 ward of the Guanggu Campus of Tongji Hospital affiliated to Huazhong University of Science and Technology in Wuhan from 1 February 2020 to 28 February 2020 were retrospectively collected and analyzed.Patients were categorized into 2 groups: the elderly group(≥60 years old)and the young and middle-aged group(<60 years old). Differences in epidemiological features, demographics, clinical symptoms, laboratory results and imaging findings between the two groups were retrospectively analyzed.Results:Among 102 patients with COVID-19, 58 were in the elderly group(≥60 years old), with a median age of 67.0(63.8, 71.0)years old, and 44 in the young and middle-aged group(<60 years old), with a median age of 47.5(38.0, 51.8)years old.There was no significant difference in gender ratio between the two groups( χ2=0.033, P=0.855). Of 102 patients, 42.0%(21/50)had close contact with an infected person, 14.0%(7/50)were from infection clusters, and 18.0%(9/50)had suspected hospital-acquired infections.Fever and cough remained the most common symptoms, but gastrointestinal symptoms such as nausea, poor appetite, diarrhea and muscle cramps were also warning signs.Fatigue and cough were the most common presenting symptoms in elderly male patients.Bilateral patchy infiltrates(57.9%, 22/38)and ground-glass opacities(42.1%, 16/38)were the main imaging features and 42.1%(16/38)patients had multiple areas of the lungs involved.Over 50% patients had increased levels of blood glucose, D-dimer, fibrinogen, C-reactive protein, procalcitonin, multiple cytokines and neutrophil-to-lymphocyte ratio, as well as decreased levels of albumin, hemoglobin, hematocrit, lymphocytes and serum calcium.Compared with the young and middle-aged group, the elderly group had higher rates of abnormality in levels of D-dimer and serum calcium( χ2=7.067 and 4.166, P=0.008 and 0.041). Conclusions:Fever and cough are the most common symptoms in elderly patients with COVID-19.Elderly patients with COVID-19 have multiple abnormalities in clinical laboratory test results, which show a certain level of specificity compared with young and middle-aged patients.
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Objective To assess value of serum level of ischemia modified albumin (IMA) in diagnosis for myocardial ischemia of coronary artery disease (CAD). Methods Seventy-two patients with clinically suspected myocardial ischemia of CAD admitted to The First People's Hospital of Hangzhou during November 2009 to May 2010 ready for undergoing coronary angiography, the gold standard for diagnosis of CAD, were randomly selected for the study. The patients were divided into CAD and non-CAD groups based on their coronary angiography. Serum level of IMA was determined with cobalt-albumin binding ( ACB) assay before coronary angiography, which served as diagnostic standard for CAD. Logistic regression analysis method was used to evaluate varied levels of IMA with area under the receiver operating characteristic curve (AUCROC) in diagnosis for myocardial ischemia of CAD. Results Mean level of IMA was (97 ±24) U/ml and (81 ±15) U/ml for CAD group (n =51) and non-CAD group (n =21), respectively. Sensitivity and specificity of a cut-off value of IMA 83.69 U/ml in diagnosis for myocardial ischemia of CAD was 80 percent and 57 percent, respectively, with a predictive value of a positive test 82 percent and that of a negative test 55 percent, respectively, from AUCROC. Logistic regression analysis demonstrated that both hypertension (P=0. 022, 6 = 1.421, OR=4. 141) and level of IMA (P=0.003, b= 1.780, OR=5.928) were independent predictors for CAD. Conclusions Sensitivity, specificity and predictive value of a positive test of the level of IMA are relatively high in diagnosis for myocardial ischemia of CAD, which is an independent predictor of it.
