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与携带多个刺突蛋白突变的 SARS-CoV-2 感染患者预后因素及结局的关系。

Association between prognostic factors and the outcomes of patients infected with SARS-CoV-2 harboring multiple spike protein mutations.

机构信息

Pediatric Surgery Division, Department of Surgery/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia.

Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

出版信息

Sci Rep. 2021 Nov 1;11(1):21352. doi: 10.1038/s41598-021-00459-4.

Abstract

The outcome of SARS-CoV-2 infection is determined by multiple factors, including the viral, host genetics, age, and comorbidities. This study investigated the association between prognostic factors and disease outcomes of patients infected by SARS-CoV-2 with multiple S protein mutations. Fifty-one COVID-19 patients were recruited in this study. Whole-genome sequencing of 170 full-genomes of SARS-CoV-2 was conducted with the Illumina MiSeq sequencer. Most patients (47%) had mild symptoms of COVID-19 followed by moderate (19.6%), no symptoms (13.7%), severe (4%), and critical (2%). Mortality was found in 13.7% of the COVID-19 patients. There was a significant difference between the age of hospitalized patients (53.4 ± 18 years) and the age of non-hospitalized patients (34.6 ± 19) (p = 0.001). The patients' hospitalization was strongly associated with hypertension, diabetes, and anticoagulant and were strongly significant with the OR of 17 (95% CI 2-144; p = 0.001), 4.47 (95% CI 1.07-18.58; p = 0.039), and 27.97 (95% CI 1.54-507.13; p = 0.02), respectively; while the patients' mortality was significantly correlated with patients' age, anticoagulant, steroid, and diabetes, with OR of 8.44 (95% CI 1.5-47.49; p = 0.016), 46.8 (95% CI 4.63-472.77; p = 0.001), 15.75 (95% CI 2-123.86; p = 0.009), and 8.5 (95% CI 1.43-50.66; p = 0.019), respectively. This study found the clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G mutation, we found L5F (18.8%), V213A (18.8%), and S689R (8.3%). No significant association between multiple S protein mutations and the patients' hospitalization or mortality. Multivariate analysis revealed that hypertension and anticoagulant were the significant factors influencing the hospitalization and mortality of patients with COVID-19 with an OR of 17.06 (95% CI 2.02-144.36; p = 0.009) and 46.8 (95% CI 4.63-472.77; p = 0.001), respectively. Moreover, the multiple S protein mutations almost reached a strong association with patients' hospitalization (p = 0.07). We concluded that hypertension and anticoagulant therapy have a significant impact on COVID-19 outcomes. This study also suggests that multiple S protein mutations may impact the COVID-19 outcomes. This further emphasized the significance of monitoring SARS-CoV-2 variants through genomic surveillance, particularly those that may impact the COVID-19 outcomes.

摘要

SARS-CoV-2 感染的结果由多种因素决定,包括病毒、宿主遗传学、年龄和合并症。本研究调查了具有多种 S 蛋白突变的 SARS-CoV-2 感染患者的预后因素与疾病结果之间的关系。本研究共招募了 51 例 COVID-19 患者。使用 Illumina MiSeq 测序仪对 170 个 SARS-CoV-2 全长基因组进行全基因组测序。大多数患者(47%)COVID-19 症状轻微,其次是中度(19.6%)、无症状(13.7%)、严重(4%)和危急(2%)。COVID-19 患者的死亡率为 13.7%。住院患者(53.4±18 岁)与非住院患者(34.6±19 岁)的年龄差异有统计学意义(p=0.001)。患者住院与高血压、糖尿病和抗凝治疗密切相关,与 OR 值为 17(95%CI 2-144;p=0.001)、4.47(95%CI 1.07-18.58;p=0.039)和 27.97(95%CI 1.54-507.13;p=0.02)显著相关;而患者的死亡率与患者年龄、抗凝、皮质类固醇和糖尿病显著相关,OR 值分别为 8.44(95%CI 1.5-47.49;p=0.016)、46.8(95%CI 4.63-472.77;p=0.001)、15.75(95%CI 2-123.86;p=0.009)和 8.5(95%CI 1.43-50.66;p=0.019)。本研究发现的分支为 L(2%)、GH(84.3%)、GR(11.7%)和 O(2%)。除了 D614G 突变外,我们还发现了 L5F(18.8%)、V213A(18.8%)和 S689R(8.3%)。多个 S 蛋白突变与患者住院或死亡率之间无显著相关性。多变量分析显示,高血压和抗凝是影响 COVID-19 住院和死亡的显著因素,OR 值分别为 17.06(95%CI 2.02-144.36;p=0.009)和 46.8(95%CI 4.63-472.77;p=0.001)。此外,多个 S 蛋白突变几乎与患者住院有很强的关联(p=0.07)。我们得出结论,高血压和抗凝治疗对 COVID-19 结果有显著影响。本研究还表明,多个 S 蛋白突变可能影响 COVID-19 结果。这进一步强调了通过基因组监测监测 SARS-CoV-2 变异的重要性,特别是那些可能影响 COVID-19 结果的变异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fae/8560824/cb20d3ee29b8/41598_2021_459_Fig1_HTML.jpg

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