Antibodies against dengue virus in COVID-19 patients in Japan: a dengue virus non-endemic country

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was associated with a global pandemic in 2020. Infection and vaccination induced a variety of immune responses in humans that differed from those observed before the pandemic. Several reports indicated that SARS-CoV-2 infection induced the production of antibodies cross-reactive to dengue virus. However, many of these reports emerged from dengue-endemic regions, and the possibility that induction of cross-reactive antibodies was affected by memory immunity induced by previous dengue virus infection could not be ruled out. Main text : In the present study, we investigated the levels of cross-reactive antibodies against dengue virus in 118 COVID-19 patients in Japan, a dengue non-endemic country. Serum samples collected from each patient during the acute and convalescent phases were analyzed using commercial IgG and IgM ELISA kits. The analysis revealed two dengue IgM-positive cases in both the acute and convalescent phases of COVID-19. These two cases showed an increasing trend of dengue IgM antibody titer in the convalescent phase. One additional case was dengue IgM-negative in the acute phase and IgM-borderline in the convalescent phase. By contrast, no cases of positive or elevated dengue IgG were observed. All 118 cases investigated in the present study lacked a history of recent travel to dengue-endemic countries. These findings suggest that SARS-CoV-2 infection induces IgM that cross-reacts with dengue virus antigens, even in the absence of immunological memory against dengue virus. Conclusions: Certain COVID-19 patients in Japan produced IgM that cross-reacted with dengue virus. Therefore, the presence of false positives should be considered in the serodiagnosis of dengue fever and COVID-19.