How super-spreader cities, highways, hospital bed availability, and dengue fever influenced the COVID-19 epidemic in Brazil

Abstract

Although its international airports served as the country's main entry points for SARS-CoV-2, the factors driving the uneven geographic spread of COVID-19 cases and deaths in Brazil remain largely unknown. Here we show that four major factors likely accounted for the entire dynamics of COVID-19 in Brazil. Mathematical modeling revealed that, initially, the "super-spreading" city of São Paulo accounted for roughly 80% of the case spread in the entire country. During the first 3 months of the epidemic, by adding only 16 other spreading cities, we accounted for 98-99% of the cases reported in Brazil at the time. Moreover, 26 of the major Brazilian federal highways accounted for about 30% of SARS-CoV-2's case spread. As cases accumulated rapidly in the Brazilian countryside, the distribution of COVID-19 deaths began to correlate with a third parameter: the geographic distribution of the country's hospital intensive care unit (ICU) beds, which is highly skewed towards state capitals where the epidemic began. That meant that severely ill patients living in the countryside had to be transported to state capitals to access ICU beds where they often died, creating a "boomerang effect" that contributed to the skew of the geographic distribution of COVID-19 deaths. Finally, we discovered that the geographic distribution of dengue fever, amounting to more than 3.5 million cases from January 2019 to July 2020, was highly complementary to that of COVID-19. This was confirmed by the identification of significant negative correlations between COVID-19's incidence, infection growth rate, and mortality to the percentage of people with antibody (IgM) levels for dengue fever in each of the country's states. No such correlations were observed when IgM data for chikungunya virus, which is transmitted by the same mosquito vector as dengue, was used. Thus, states in which a large fraction of the population had contracted dengue fever in 2019-2020 reported lower COVID-19 cases and deaths, and took longer to reach exponential community transmission, due to slower SARS-CoV-2 infection growth rates. This inverse correlation between COVID-19 and dengue fever was further observed in a sample of countries around Asia and Latin America, as well as in islands in the Pacific and Indian Oceans. This striking finding raises the intriguing possibility of an immunological cross-reactivity between DENV serotypes and SARS-CoV-2. If proven correct, this hypothesis could mean that dengue infection or immunization with an efficacious and safe dengue vaccine could produce some level of immunological protection for SARS-CoV-2, before a vaccine for SARS-CoV-2 becomes available.

Clinical and biochemical parameters of COVID-19 patients with prior or active dengue fever

“…Despite the number of patients and our cohort's convenience sample nature, our observation points to the significant proportion of COVID-19 patients in the Federal District which are actually undergoing a SARS-CoV-2/dengue virus co-infection. Also, the percentage of COVID-19 patients with dengue fever history disagrees with a recently published mathematical model that demonstrated a negative correlation between COVID-19 and dengue fever infection in Brazilian patients ( Nicolelis et al, 2020 ). Different from Nicolelis et al (2020) , we did not observe any indication that the infection with dengue virus could protect patients against SARS-CoV-2.…”

“…Also, the percentage of COVID-19 patients with dengue fever history disagrees with a recently published mathematical model that demonstrated a negative correlation between COVID-19 and dengue fever infection in Brazilian patients ( Nicolelis et al, 2020 ). Different from Nicolelis et al (2020) , we did not observe any indication that the infection with dengue virus could protect patients against SARS-CoV-2. In our hands, COVID-19/past dengue fever patients represented a significant fraction of our sample and presented similar clinical parameters to COVID-19 patients.…”

Characteristics of patients coinfected with Severe Acute Respiratory Syndrome Coronavirus 2 and dengue virus, Lambayeque, Peru, May–August 2020: A retrospective analysis

“…Thus, we have that in some cities in Brazil, it was observed that states in which a significant fraction of the population had contracted dengue fever in 2019–2020 reported fewer cases and deaths from COVID-19, and took longer to achieve exponential community transmission because the growth rates of SARS-CoV-2 infection are slower. This inverse correlation between COVID-19 and Dengue was observed in a sample of countries in Asia and Latin America and islands in the Pacific and Indian oceans [ 39 ].…”

A steady trickle-down from metro districts and improving epidemic-parameters characterized the increasing COVID-19 cases in India

“…[5] In another recent study on COVID-19 in Brazil, the connectivity between different cities via highways was attributed to be one of the reasons for super-spreading across major cities. [13] However, the work did not establish any patterns for the spread of the active-case burden or its flattening,[14] which is extremely important in an epidemic or a pandemic from the public health point-of-view.…”