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 dengueendemic countries and vice versa especially during the active years of the pandemic (2019-2021). We observed that dengue virus (DENV) antibodies (Abs) could crossreact 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 crossneutralize 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.

Pre-dominance of dengue non-cross-reacting SARS-CoV-2 spike antibodies during the Omicron era and their role in the ADE-mediated surge of Dengue virus serotype 3

“…Antibodies raised against the receptor-binding domain (RBD) of S1 subunit of SARS-CoV-2 spike protein and serum samples from COVID-19 patients were shown to neutralize DV2 in a subsequent investigation from Taiwan 10 . All these studies confirmed that there is indeed, an antigenic relationship between SARS-COV-2 and DV and the two viruses are co-evolving under self and mutually cross-reactive immune selection pressures in regions where they are co-endemic now 3 .…”

“…Patients-S04, S16 and S25) as well as DV4 (e.g.Patients-S02, S05). This observation perhaps provides one strong evidence as to why DV cases were reportedly decreased in India and many other dengue endemic regions like Indonesia, Sri Lanka and Guangzhou, China3,30 during the COVID-19 Delta wave (2020-2021). During this time, the predominant SARS-CoV-2 Abs were DV cross-reactive7 and could "cross-neutralize" DV1-4.…”

“…We had previously discussed that following the decline of DV cases during the active years of the pandemic (2020-21), there was a surge in DV3 cases observable from the late months of 2022 onwards in Southeast Asia including West Bengal, India, Bangladesh and Singapore 3, 38 . In the present times DV3 cases are being increasingly reported even from non-DV3 endemic countries like Brazil and Nigeria 15, 16, 39 .…”

“…COVID-19 has posed a major hazard to public health worldwide 1 . We had observed that SARS-CoV-2 showed a trend of decreased transmission, severity and overall fatality per million populations in the highly dengue-endemic regions 2, 3 . Computational modeling studies from our laboratory supported the hypothesis that dengue virus (DV) (Family: Flaviviridae ) envelope antibodies (Abs) can bind to SARS-CoV-2 receptor binding sites 4 .…”

Unravelling Antigenic Cross-Reactions toward the World of Coronaviruses: Extent of the Stability of Shared Epitopes and SARS-CoV-2 Anti-Spike Cross-Neutralizing Antibodies

“…There are still teams that seek to identify a variant-proof strategy for the development of a pan-betacoronaviruses vaccine formulation [ 38 , 171 , 172 , 173 ]. Additional hypotheses refer to as cross-reaction between dengue virus (DENV) antibodies and the SARS-CoV-2 S1 RBD [ 174 ]. Regarding pre-pandemic natural immunity against SARS-CoV-2, further investigations in Africa are required to determine if there could be an exception on this continent, on which contact with wild animals (and therefore the risk of infection by animal viruses) is more frequent than elsewhere, possibly contributing to curbing the pandemic.…”