Dengue virus (DV) non-cross-reactive Omicron wave COVID-19 serums enhanced DV3 infectivity in vitro.

Introduction. In India, the SARS-CoV-2 Delta wave (2020-2021) faded away with the advent of the Omicron variants (2021-present). Dengue incidences were observed to be less in Southeast Asia during the active years of the pandemic (2020-2021). However, dengue virus type 3 (DV3) cases were increasingly reported in this region (including India) concurrent with the progression of the Omicron waves since 2022.Hypothesis. What could be the reason(s) behind this unusual DV3 surge after an overall dip in dengue incidences in many parts of Southeast Asia?Aim. We, therefore, investigated the current state of cross-reactivity of prevalent (Omicron era) SARS-CoV-2 serums with different DV serotypes and evaluated the impact of such serums on DV neutralization in cell culture.Methodology. Fifty-five COVID-19 serum samples (January-September 2022) and three pre-pandemic archived serum samples from apparently healthy individuals were tested for DV or SARS-CoV-2 IgM/IgG using the lateral flow immunoassays. DV1-4 virus neutralization tests (VNTs) were done with the SARS-CoV-2 antibody (Ab)-positive serums in Huh7 cells. DV3 envelope (env) gene was PCR amplified and sequenced for three archived DV isolates, one from 2017 and two from 2021.Results. SARS-CoV-2 Ab-positive samples constituted 74.5 % of the serums. Of these, 41.5 % were DV cross-reactive and 58.5 % were not. The DV cross-reactive serums neutralized all DV serotypes (DV1-4), as per previous results and this study. The DV non-cross-reactive serums (58.5 %) also cross-neutralized DV1, 2 and 4 but increased DV3 infectivity by means of antibody-dependent enhancement of infection as evident from significantly higher DV3 titres in VNT compared to control serums. The DV3 envelope was identical among the three isolates, including isolate 1 used in VNTs. Our results suggest that DV cross-reactivity of SARS-CoV-2 serums diminished with the shift from Delta to Omicron prevalence. Such COVID-19 serums (DV non-cross-reactive) might have played a major role in causing DV3 surge during the Omicron waves.Conclusion. Patients suspected of dengue or COVID-19 should be subjected to virus/antigen tests and serological tests for both the diseases for definitive diagnosis, prognosis and disease management.

Evidences support that dengue virus can impart broad-spectrum immunity against betacoronaviruses in dengue endemic regions.

COVID-19 tended to be less aggressive in dengue endemic regions. Conversely, dengue cases plummeted in dengue endemic zones during the active years of the pandemic (2020-2021). We and others have demonstrated serological cross-reactivity between these two viruses of different families. We further demonstrated that COVID-19 serum samples that were cross-reactive in dengue virus (DV) serological tests, "cross-neutralized" all DV serotypes in Huh7 cells. Here we showed by co-immunoprecipitation (Co-IP) and atomic force microscopy (AFM) imaging that severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 (SARS-CoV-2) spike (S) protein subunit S1 and S2 monoclonal antibodies can indeed, bind to DV particles. Likewise, DV envelope antibodies (DV E Abs) showed high docking frequency with other human pathogenic beta-CoVs and murine hepatitis virus-1 (MHV-1). SARS-CoV-2 Ab didn't show docking or Co-IP with MHV-1 supporting poor cross-protection among CoVs. DV E Abs showed binding to MHV-1 (AFM, Co-IP, and immunofluorescence) and prepandemic dengue patients' serum samples even "cross-neutralized" MHV-1 plaques in cell culture. Furthermore, dengue serum samples showed marked inhibition potential in a surrogate virus-based competitive enzyme-linked immunosorbent assay, used for determining neutralizing Abs against SARS-CoV-2 S protein receptor-binding domain in COVID-19 serum samples. We therefore, provide multiple evidence as to why CoVs are epidemiologically less prevalent in highly dengue endemic regions globally.

COVID-19 serum can be cross-reactive and neutralizing against the dengue virus, as observed by the dengue virus neutralization test.

OBJECTIVES: Observing the serological cross-reactivity between SARS-CoV-2 and dengue virus (DV), we aimed to elucidate its effect on dengue serodiagnosis and infectivity in a highly dengue-endemic city in India. METHODS: A total of 52 COVID-19 (reverse transcription-polymerase chain reaction [RT-PCR] positive) serum samples were tested in rapid lateral flow immunoassays and DV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) to detect DV or SARS-CoV-2 IgG/immunoglobulin M. The COVID-19 antibody (Ab) positive samples were subjected to a virus neutralization test (Huh7 cells) using DV type 1 (DV1) clinical isolate. RESULTS: Most (93%) of the SARS-CoV-2 Ab-positive serum samples cross-reacted with DV in rapid or ELISA tests. All were DV RNA and nonstructural protein 1 (NS1) antigen-negative. COVID-19 serum samples that were DV cross-reactive neutralized DV1. Of these, 57% had no evidence of DV pre-exposure (DV NS1 Ab-negative). The computational study also supported potential interactions between SARS-CoV-2 Ab and DV1. CONCLUSION: DV serodiagnosis will be inconclusive in areas co-endemic for both viruses. The COVID-19 pandemic appears to impart a protective response against DV in DV-endemic populations.

Archived dengue serum samples produced false-positive results in SARS-CoV-2 lateral flow-based rapid antibody tests.

Co-endemicity of SARS-CoV-2 and dengue virus (DV) infection is becoming a matter of serious concern as it has been already reported that antibodies (Ab) elicited by SARS-CoV-2 infection can produce false-positive results in dengue IgG and IgM rapid tests and vice versa. Here we communicate that five of thirteen DV antibody-positive serum samples from Kolkata, archived in 2017 (predating the COVID-19 outbreak), produced false-positive results in SARS-CoV-2 IgG/IgM lateral flow-based rapid tests. Our results emphasize the importance of implementing tests with higher specificity to conduct sero-surveillance for accurate estimation of SARS-CoV-2/DV prevalence in regions where both viruses now co-exist.

Computational modelling supports that dengue virus envelope antibodies can bind to SARS-CoV-2 receptor binding sites: Is pre-exposure to dengue virus protective against COVID-19 severity?

The world is going through the scourge of the COVID-19 pandemic since January 2020. However, the pandemic appears to be less severe in highly dengue endemic countries. In this connection, several studies reported that sero-diagnostic tests for dengue virus (DV) yielded considerable false-positive results for SARS-CoV-2 and vice versa in dengue endemic regions, thereby indicating towards potential cross-reactivity between these two viruses. We anticipated that SARS-CoV-2 and DV might share antigenic similarity and performed computational docking studies to test this hypothesis. Our results predicted with high confidence that human DV antibodies can indeed, bind to RBD of SARS-CoV-2 Spike protein. Some of these interactions can also potentially intercept human ACE2 receptor binding to RBM. Dengue serum samples predating the COVID-19, had been found to cross-react with SARS-CoV-2 Spike and this provides direct experimental validation of our predictions. Our analysis also showed that m396 and 80R antibodies (against SARS-CoV-1) did not dock with RBM of SARS-CoV-2, a fact already proven experimentally. This confirmed reliability and robustness of our approach. So, it is highly probable that immunological memory/antibodies to DV in endemic countries may reduce the severity and spread of COVID-19. It is not known whether SARS-CoV-2 antibodies will hinder DV infections by binding to DV particles and reduce dengue incidences in the future or, augment DV infection and severity by deploying antibody-dependent enhancement.