Differential Protein Expression in Dengue Patients with SARS-CoV-2 IgG Antibodies: Implications of Disease Severity and Antibody Dependent Enhancement

Dengue is the most prevalent arthropod-borne disease, causing 100-400 million infections annually. The clinical symptoms range from asymptomatic to severe, involving hemorrhage and organ failure. Severe dengue often occurs in secondary infections with different serotypes due to antibody-dependent enhancement (ADE). During the SARS-CoV-2 pandemic, cross-reactions between dengue and SARS-CoV-2 antibody tests have been reported, due to antibody cross-reactivity between the dengue envelope protein and SARS-CoV-2 S1-RBD protein. This study analyzed the serum proteome of dengue patients with and without SARS-CoV-2 IgG antibodies. We conducted a bottom-up label-free proteomic analysis of whole serum samples from healthy donors and dengue patients, with or without SARS-CoV-2 IgG antibodies. We identified 1,122 protein sequences, 296 of which were gene-associated. Gene ontology analysis revealed that dengue patients with both SARS-CoV-2 and dengue IgG antibodies had more genes involved in immune regulation, humoral response, blood coagulation, and platelet degranulation, which may increase severe dengue risk. Unique proteins linked to platelet activation, such as coagulation factor XIII B chain, thrombospondin, Antigen KI-67, bone marrow proteoglycan, and colorectal cancer mutant protein may explain thrombocytopenia mechanisms. Our results indicate that SARS-CoV-2 IgG antibodies in dengue infection cause differential protein expression compared with healthy donors or other groups.