Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients With Acute Febrile Illness

United States and Puerto Rico, April 2020-March 2021

Jorge Munoz-Jordan; Jaime Cardona; Manuela Beltrán; Candimar Colón; Jarad Schiffer; Evelene Stewart-Clark; Briana Zellner; Vera Semenova; Yikun Li; Lily Tao Jia; Panagiotis Maniatis; Lucia Pawloski; Laura Adams; Gabriela Paz-Bailey; Vanessa Rivera-Amill; Freddy Medina


Morbidity and Mortality Weekly Report. 2022;71(10):375-377. 

In This Article


The results obtained for DENV and Zika virus IgM and SARS-CoV-2 antibodies evaluated with the tests described in this study indicated high specificity and minimal levels of cross-reactivity between the two flaviviruses (DENV and Zika virus) and SARS-CoV-2. A previous study reported a similar test specificity of the SARS-CoV-2 pan-Ig Spike Protein ELISA assay (99%) for pathogens unrelated to those evaluated in this study,[7] and similarly high levels of specificity (97%) have been reported for the DENV Detect IgM Capture ELISA.[9]

The findings in this report are subject to at least three limitations. First, the study was conducted with tests used at CDC laboratories for reference testing and do not constitute a direct assessment of other available tests. In addition, selection of specimens from acute and early convalescent phases of disease is based on the recommended time for dengue disease diagnosis; therefore, this study does not address cross-reactivity after day 9 of symptoms, when antibody levels might be higher than those detected during disease. The study did not assess cross-reactivity from COVID-19 vaccine-elicited antibodies. Finally, sampling in this study does not address the contribution of previously acquired IgG antibodies to the specificity of these tests.

These findings indicate that in a cohort of patients in Puerto Rico, where dengue disease is endemic, the serologic diagnosis of dengue disease with a commonly used IgM test is not affected by antibodies to SARS-CoV-2, nor do Zika virus and DENV IgM antibodies interfere with SARS-CoV-2 antibody detection. These results suggest that previously reported cross-reactivity between these viruses appears to be nonspecific and not a result of actual cross-reactivity from shared or similar epitopes. A possible explanation for these apparent cross-reactive results might be the presence of antibodies from a recent flavivirus infection in COVID-19 patients in areas of co-endemicity. Therefore, routine testing algorithms established for dengue and Zika diseases with the assays described in this report can proceed with the understanding that the chances of misdiagnosis of dengue or Zika virus diseases are not augmented by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.