Interacting Epidemics in Amazonian Brazil: Prior Dengue Infection Associated with Increased 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 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 IgG was found in 37.0% of 1,285 cohort participants (95% confidence interval [CI], 34.3% to 39.7%) in 2019, with 10.4 (95% CI, 6.7 to 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 y were twice more likely to have symptomatic COVID-19 than under-five children. 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 0.025 and 0.039 after adjustment for identified confounders. Conclusion 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.