Potential antigenic cross-reactivity between SARS-CoV-2 and Dengue viruses

Background 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 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 nine cases of positive IgM, two cases of positive IgG and one case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in two 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%) (sixteen IgA, five IgG) versus four 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.