Cross‐reactivity of SARS‐CoV‐2 with other pathogens, especially dengue virus: A historical perspective

Abstract Dengue is a vector‐borne viral disease caused by a Flavivirus whereas the COVID‐19 pandemic was caused by a highly contagious virus, SARS‐CoV‐2 belonging to the family Coronaviridae . However, COVID‐19 severity was observably less in dengue‐endemic countries and vice versa especially during the active years of the pandemic (2019–2021). We observed that dengue virus (DENV) antibodies (Abs) could cross‐react with SARS‐CoV‐2 spike antigen. This resulted in SARS‐CoV‐2 false positivity by rapid Ab test kits. DENV Abs binding to SARS‐CoV‐2 receptor‐binding domain (and the reverse scenario), as revealed by docking studies further validated DENV and SARS‐CoV‐2 cross‐reactivity. Finally, SARS‐CoV‐2 Abs were found to cross‐neutralize DENV1 and DENV2 in virus neutralization test (VNT). Abs to other pathogens like Plasmodium were also cross‐reactive but non‐neutralizing for SARS‐CoV‐2. Here, we analyze the existing data on SARS‐CoV‐2 cross‐reactivity with other pathogens, especially dengue to assess its impact on health (cross‐protection?) and differential sero‐diagnosis/surveillance.