Interacting Epidemics in Amazonian Brazil: Prior Dengue Infection Associated With Increased Coronavirus Disease 2019 (COVID-19) Risk in a Population-Based Cohort Study

Abstract Background Immunity after dengue virus (DENV) infection has been suggested to cross-protect from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. Methods We tested whether serologically proven prior DENV infection diagnosed in September–October 2019, before the coronavirus disease 2019 (COVID-19) pandemic, reduced the risk of SARS-CoV-2 infection and clinically apparent COVID-19 over the next 13 months in a population-based cohort in Amazonian Brazil. Mixed-effects multiple logistic regression analysis was used to identify predictors of infection and disease, adjusting for potential individual and household-level confounders. Virus genomes from 14 local SARS-CoV-2 isolates were obtained using whole-genome sequencing. Results Anti-DENV immunoglobulin G (IgG) was found in 37.0% of 1285 cohort participants (95% confidence interval [CI]: 34.3% to 39.7%) in 2019, with 10.4 (95% CI: 6.7–15.5) seroconversion events per 100 person-years during the follow-up. In 2020, 35.2% of the participants (95% CI: 32.6% to 37.8%) had anti-SARS-CoV-2 IgG and 57.1% of the 448 SARS-CoV-2 seropositives (95% CI: 52.4% to 61.8%) reported clinical manifestations at the time of infection. Participants aged >60 years were twice more likely to have symptomatic COVID-19 than children under 5 years. Locally circulating SARS-CoV-2 isolates were assigned to the B.1.1.33 lineage. Contrary to the cross-protection hypothesis, prior DENV infection was associated with twice the risk of clinically apparent COVID-19 upon SARS-CoV-2 infection, with P values between .025 and .039 after adjustment for identified confounders. Conclusions Higher risk of clinically apparent COVID-19 among individuals with prior dengue has important public health implications for communities sequentially exposed to DENV and SARS-CoV-2 epidemics. Serologically proven prior dengue infection is associated with increased subsequent risk of clinically apparent coronavirus disease 2019 (COVID-19) in Amazonians, implying that sequential dengue and COVID-19 epidemics may impose an extra burden of disease to affected communities in the tropical and subtropical world.