Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat Gan, Israel.
Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
Clin Infect Dis. 2021 Oct 5;73(7):e2444-e2449. doi: 10.1093/cid/ciaa1207.
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.
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.
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.
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.
由于临床和实验室特征相似，2019 年冠状病毒病（COVID-19）和登革热难以区分。由于登革热血清学假阳性而未能考虑 COVID-19 可能会产生严重后果。我们旨在评估这种可能的交叉反应。
我们分析了 55 例严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染患者的临床数据和血清样本。为了评估登革热血清学状态，我们使用了侧向流动快速检测的登革热特异性抗体，以及酶联免疫吸附试验（ELISA）。此外，我们对患有登革热的患者进行了 SARS-CoV-2 血清学检测，并进行了蛋白质结构的计算机模拟分析以识别表位相似性。
使用登革热侧向流动快速检测，我们在 55 例 COVID-19 患者中检测到 12 例阳性病例（21.8%），而在 70 例健康对照者中则无阳性病例（P = 2.5E-5）。这包括 9 例免疫球蛋白 M（IgM）阳性、2 例免疫球蛋白 G（IgG）阳性和 1 例 IgM 和 IgG 抗体阳性。使用针对包膜蛋白的抗体对另外 2 例患者进行 ELISA 检测，发现登革热呈阳性。在 2019 年 9 月之前诊断为登革热的 95 例患者的样本中，针对 S 蛋白的 SARS-CoV-2 血清学检测在 21 例（22%）中呈阳性/不确定（16 例 IgA，5 例 IgG），而在 102 例对照者（4%）中则有 4 例阳性/不确定（P = 1.6E-4）。随后的计算机模拟分析显示，SARS-CoV-2 刺突蛋白 HR2 结构域中的表位与登革热包膜蛋白之间可能存在相似性。
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 患者的登革热血清学假阳性，反之亦然。这可能对患者护理和公共卫生都产生严重后果。
