Cross-reactivity between dengue virus and SARS-CoV-2 antibodies: Confirmation study using specimens from dengue-infected patients before the COVID-19 pandemic

Background: The simultaneous occurrence of the COVID-19 pandemic and a dengue outbreak has posed significant challenges for governments and medical personnel in dengue-endemic countries like Indonesia. Several studies in dengue-endemic countries have reported cases of misdiagnosis between COVID-19 and dengue. Therefore, it is crucial to evaluate the potential cross-reactivity between SARS-CoV-2 antibodies and dengue. Methods: This study aimed to confirm the serological cross-reaction between dengue virus and SARS-CoV-2 in Surabaya, East Java, which is a highly dengue-endemic city in Indonesia. In total, 238 serum samples with confirmed dengue that were collected before the emergence of COVID-19 were tested to detect the presence of reacting IgG and IgM antibodies (Abs) against SARS-CoV-2 via a rapid detection test (RDT) and enzyme-linked immunosorbent assay (ELISA). Samples from patients with dengue infection collected during the pandemic, from healthy volunteers predating the pandemic, and from patients with COVID-19 were used for comparison. Results and conclusion: Few (6.7 %) of the pre-COVID-19 dengue Ab-positive serum samples showed reactive on SARS-CoV-2 in the RDT, with significantly lower IgG and IgM levels detected in ELISA compared with the dengue samples collected during the pandemic and the COVID-19 samples (P < 0.005). A comparable anti-SARS-CoV-2 IgG concentration was observed in the pre-COVID-19 dengue samples and healthy volunteers (P = 0.56), which also indicated other possibilities. In conclusion, our results suggested a low risk of cross-reactivity between dengue virus and SARS-CoV-2. However, they highlighted the need for caution when using and interpreting data obtained stemming from serological methods, to prevent false-positive results. Further studies are needed to evaluate the cross-reactivity between dengue virus, SARS-CoV-2, and other common human pathogens, as well as its effect on the serosurveys, treatment of these diseases, or vaccine efficacy.