bats vs mosquitos
Image Credit: Gulf News / Jay Hilotin

Dubai: Could a previous dengue virus infection confer protection against SARS-CoV-2? Answer: There appears to be an “inverse correlation” between the two, said researchers. Translation: The higher past dengue cases were recorded in a specific geographic location, the lower the number of COVID-19 cases.

The reason: In a published study that’s not been peer-reviewed yet, researchers from Duke University, University of Sao Paolo, Federal University of Paraiba and the Oswaldo Cruz Foundation, had made a surprising discovery: data related to the two viral infections showed a correlation between COVID-19 and dengue virus (DENV) fever.

4.94m

COVID-19 cases recorded in Brazil as of October 5, 2020

The research was published September 21, 2020 on Medrxiv, a pre-print scientific server. It was conducted by a team led by Dr Miguel Nicolelis, which cited the data primarily from Brazil, where there’s been a high rate of dengue cases both past and present.

In terms of geographic distribution, researchers found that more than 3.5 million cases of dengue recorded from January 2019 to July 2020 was “highly complementary” to that of COVID-19.

COVID-19 cases
As of October 5, 2020 Brazil reported 11,946 new COVID-19 infections in one day, bringing the total cases to 4.94 million and 147,000 deaths, with 4.3 million recoveries, according to latest WHO data.

'Negative correlation'

“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,” the researchers stated, citing official data from Brazils health authorities.

Dr Nicolelis works at the Department of Neurobiology, Duke University Medical Center, in North Carolina USA. His team found that in the Latin American country, 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.”

An aedes aegypti mosquito and an electronic-microscope magnified dengue virus.
ACCIDENTAL DISCOVERY: An aedes aegypti mosquito and an electronic-microscope magnified dengue virus. The researchers 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.

The comparative data also included those taken from tropical regions of the world. Indeed, the researchers stated, this inverse correlation between COVID-19 and dengue fever was also observed in a sample of countries around Asia and Latin America, as well as in islands in the Pacific and Indian Oceans.

SUPER-SPREADING CITY
Mathematical modeling revealed that, initially, the “super-spreading city” of São Paulo accounted for roughly 80% of the case spread in the whole of Brazil. During the first 3 months of the epidemic, by adding only 16 other spreading cities, these 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 SARSCoV-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.

“This striking finding raises the intriguing possibility of an immunological cross-reactivity between Dengue virus (DENV) serotypes and SARS-CoV-2.” Nicolelis earlier told Reuters the results are particularly interesting because previous studies have shown that people with dengue antibodies in their blood can test falsely positive for COVID-19 antibodies even if they have never been infected by the coronavirus.

No such correlations were observed when IgM data for chikungunya virus, which is transmitted by the same mosquito vector as dengue, was used. The study’s results are preliminary. But the researchers said that if proven correct, their hypothesis could mean that dengue infection or immunisation 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.

What was the research based on?

The data-driven research analyzed the coronavirus outbreak in Brazil. It mainly focussed on how super-spreader cities, highways, hospital bed availability, and dengue fever influenced the COVID-19 epidemic in Brazil.

What are the findings?

The researchers found that places with lower coronavirus infection rates and slower case growth were locations that had suffered intense dengue outbreaks this year or last.

It indicates that there is an immunological interaction between two viruses that nobody could have expected, because the two viruses are from completely different families.“This striking finding raises the intriguing possibility of an immunological cross-reactivity between dengue’s Flavivirus serotypes and SARS-CoV-2,” the study said, referring to dengue virus antibodies and the novel coronavirus.

Who is behind the study?

The study was led by Miguel Nicolelis, a professor at Duke University. He was joined by Rafael L. G. Raimundo, Rafael L. G. Raimundo of Federal University of Paraíba in Rio Tinto; Pedro S. Peixoto, of the University of Sao Paolol and Cecilia Siliansky de AndreazziPedro S. Peixoto; and Cecilia Siliansky de Andreazzi or Oswaldo Cruz Foundation, a biological research and development institution based Rio de Janeiro, Brazil.

What are the implications of the study?

It suggests exposure to the mosquito-transmitted illness may provide some level of immunity against COVID-19. 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” against the coronavirus, it added.

What are the limitations of the study?

Through the Dengue-COVID-19 inverse correlation was seen, further studies are needed to prove the connection. It highlights a significant correlation between lower incidence, mortality and growth rate of COVID-19 in populations in Brazil where the levels of antibodies to dengue were higher. Brazil has the world’s third highest total of COVID-19 infections with more than 4.4 million cases - behind only the United States and India.

Which Brazilian states had high dengue incidents?

In states such as Paraná, Santa Catarina, Rio Grande do Sul, Mato Grosso do Sul and Minas Gerais, had a high incidence of dengue in 2019 and 2020 (data till July 2020). In this states, researchers found that COVID-19 took much longer to reach a level of high community transmission — compared to states such as Amapá, Maranhão and Pará that had fewer dengue cases. The team found a similar relationship between dengue outbreaks and a slower spread of COVID-19 in other parts of Latin America, as well as Asia and islands in the Pacific and Indian Oceans.

How did they discover the correlation?

It was by accident. The researchers were conducting a study focused on how COVID-19 had spread through Brazil. The team said they discovered the dengue-COVID inverse correlation “by accident”. The study found that highways played a major role in the distribution of cases across the country. After identifying certain case-free spots on the map, the team went in search of possible explanations. A breakthrough came when the team compared the spread of dengue with that of the coronavirus. “It was a shock. It was a total accident,” Nicolelis said. “In science, that happens, you’re shooting at one thing and you hit a target that you never imagined you would hit.”