Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses
Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses
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DOI：
10.1093/cid/ciaa1207
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发表时间：
2021-10-01
影响因子：
11.8
通讯作者：
Vivante, Asaf
中科院分区：
文献类型：
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作者：
Lustig, Yaniv;Keler, Shlomit;Vivante, Asaf
背景。鉴于 2019 年冠状病毒病 (COVID-19) 和登革热具有共同的临床和实验室特征，因此很难区分。由于登革热血清学假阳性而未能考虑 COVID-19 可能会产生严重影响。我们旨在评估这种可能的交叉反应性方法。我们分析了 55 名严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染者的临床数据和血清样本。为了评估登革热血清学状态，我们通过侧流快速检测以及酶联免疫吸附测定（ELISA）使用登革热特异性抗体。此外，我们还测试了登革热患者的 SARS-CoV-2 血清学状态，并进行了计算机模拟蛋白质结构分析，以确定表位相似性。结果。使用登革热侧流快速检测，我们在 55 名 (21.8%) 例 COVID-19 患者中检测到 12 例阳性病例，而在由 70 名健康个体组成的对照组中检测到零例阳性病例 (P = 2.5E-5)。其中免疫球蛋白M（IgM）阳性9例，免疫球蛋白G（IgG）阳性2例，IgM和IgG抗体阳性1例。使用包膜蛋白定向抗体对另外 2 名受试者进行登革热 ELISA 检测呈阳性。在 2019 年 9 月之前从诊断为登革热的患者中获取的 95 份样本中，针对 S 蛋白的 SARS-CoV-2 血清学结果在 21 份（22%）（16 份 IgA、5 份 IgG）中呈阳性/模棱两可，而在 102 份对照（4%）中，有 4 份呈阳性/模棱两可（P = 1.6E-4）。随后的计算机分析揭示了刺突蛋白 HR2 结构域中的 SARS-CoV-2 表位与登革热包膜蛋白之间可能存在的相似性。结论。我们的研究结果支持登革热病毒和 SARS-CoV-2 之间可能存在交叉反应，这可能导致 COVID-19 患者出现登革热血清学假阳性，反之亦然。这可能会对患者护理和公共卫生产生严重后果。
Background. Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity.Methods. We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities.Results. Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID- 19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E-5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E-4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein.Conclusions. Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.