ABSTRACT
Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.
ABSTRACT
Background: A few patients with coronavirus disease 2019 (COVID-19) may progress into irreparable outcomes. Early identification of patients with serious symptoms who may develop critical illness and even death is of considerable importance for personalizing treatment and balancing medical resources.Methods: In this retrospective study, demographic, clinical characteristics and laboratory tests from 726 patients with serious COVID-19 from Tongji Hospital (Wuhan, China) were analyzed. The standards for the serious type are guided by the Chinese management guideline for COVID-19. Patients were classified into critical group (174 cases) and severe group (552 cases) based on whether the composite endpoint was reached, and the former group was divided into the survivors (47 cases) and non-survivors (127 cases). Univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were performed to investigate the risk factors associated with poor prognosis and mortality outcomes.Results: Male patients accounted for 62.1% and 51.6% in the critical group and severe group, with a median age of 68 and 65 years, respectively. Among critical cases there was a higher prevalence of chronic obstructive lung disease (p = 0.029) and chest distress (p = 0.040) than in severe cases. In the multivariable analysis, the risk factors associated with poor prognosis in severe cases were advanced age (p = 0.002), high respiratory rate (RR) (p < 0.0001), high lactate dehydrogenase (LDH) level (p = 0.021), high hypersensitive cardiac troponin I (hs-cTnI) level (p < 0.0001), and low platelet counts (p = 0.005) at admission. In the adjusted models, higher mortality outcomes in critical patients were associated with high hs-cTnI level (p = 0.037). By plotting ROC curves of different indices, hs-cTnI and LDH were found to be predictive factors for poor prognosis in patients with severe COVID-19.Conclusions: For the risk assessment of serious COVID-19 patients on admission, advanced age, high level of RR, LDH, hs-cTnI, and low platelet counts, constitute important risk factors for poor prognosis in severe cases, and the hs-cTnI level can be helpful in predicting fatal outcomes in critically ill patients.