Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses

Yaniv Lustig, Shlomit Keler, Rachel Kolodny, Nir Ben-Tal, Danit Atias-Varon, Ekaterina Shlush, Motti Gerlic, Ariel Munitz, Ram Doolman, Keren Asraf, Liran I. Shlush, Asaf Vivante

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)E2444-E2449
JournalClinical Infectious Diseases
Issue number7
StatePublished - 5 Oct 2021

Bibliographical note

Funding Information:
Y. L. is supported by the Nehemia Rubin Excellence in Biomedical Research—The TELEM Program. L. I. S. is an incumbent of the Ruth and Louis Leland career development chair. This research was also supported by the Sagol Institute for Longevity Research, the Barry and Eleanore Reznik Family Cancer Research Fund, Steven B. Rubenstein Research Fund for Leukemia and Other Blood Disorders, the Rising Tide Foundation, and the Applebaum Foundation. R. K. and N. B.-T. acknowledge the support of ISF grant 450/16 of the Israeli Science Foundation (ISF). N. B.-T.’s research is supported in part by the Abraham E. Kazan Chair in Structural Biology, Tel Aviv University.

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.


  • COVID-19
  • West Nile
  • dengue

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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