UF-led study explores differences in Covid-19 severity internationally

Health care workers and a community liaison work at a field site in Kinshasa, Democratic Republic of Congo.
Health care workers and a community liaison (standing) work at a field site in Kinshasa, Democratic Republic of Congo for previous infectious disease research by Rhoel Dinglasan, Ph.D., M.P.H., and his team before the COVID-19 pandemic. Dinglasan will use the same field sites for a new project examining factors influencing COVID-19 severity in sub-Saharan Africa. (Photo by Rhoel Dinglasan)

The question kept coming up: Why are some countries in the grip of COVID-19 while others appear less affected?

“It’s fundamentally curious,” said Rhoel Dinglasan, Ph.D., M.P.H., a professor of infectious diseases with the University of Florida College of Veterinary Medicine. “It seems like COVID-19 is not affecting people in Africa as severely as it has in North America. But why?”

Dinglasan suspects the answer is connected to people’s exposure to infectious diseases in specific geographic regions.

The U.S. Centers for Disease Control and Prevention recently awarded a $10 million grant to a team led by Dinglasan to test this hypothesis and explore other factors that can influence COVID-19 severity. Other investigators from UF include John Lednicky, Ph.D., a professor in the College of Public Health and Health Professions; Piyush Jain, Ph.D., an assistant professor of chemical engineering in the Herbert Wertheim College of Engineering; and Sadie Ryan, Ph.D., an associate professor of medical geography in the College of Liberal Arts and Sciences.

The team and its international collaborators will study the current and past history of people’s exposure to the SARS-CoV-2 virus, and its genetic variants, that cause COVID-19 in two African countries, along with other factors. The project will also use engineered CRISPR-based genetic tests for detecting SARS-CoV-2 and other pathogens. The Democratic Republic of Congo and Nigeria have so far reported fewer infections and deaths due to COVID-19 compared with heavily affected western countries, Dinglasan said. The researchers will coordinate closely with the Africa Centres for Disease Control and Prevention to characterize host and pathogen features that differentiate the pandemic experience of the United States and sub-Saharan countries.

Dinglasan, who is also affiliated with the UF Emerging Pathogens Institute, is well acquainted with human and zoonotic diseases that are endemic to sub-Saharan Africa. His work has primarily focused on vector-borne diseases, such as malaria and arboviruses like West Nile, dengue and Zika.

The idea for the current COVID-19 comparative project was born out of curiosity. Dinglasan couldn’t help but notice that, compared with Florida, severe COVID-19 didn’t appear as widespread at many of the sites in the Democratic Republic of Congo where he conducts malaria research. It could be that these areas have tested fewer people compared with other countries, but Dinglasan suspects this alone does not fully explain the disparity.

“Although lack of testing capacity may explain differences in case numbers, the lower number of severe cases leading to death suggests that other factors may be influencing the local COVID-19 epidemic in each country,” said Dinglasan. “When we remove mitigation strategies such as testing, masking, physical distancing and vaccination, we are left looking at what endemic diseases people in other countries are experiencing as the influencing factors.”

Common parasitic infections found in sub-Saharan Africa, such as malaria and schistosomiasis, can suppress the immune system, which might then prevent severe COVID-19 from developing, he said. A dampened immune response during a SARS-CoV-2 infection can, in turn, prevent the cascade of hyperinflammation that often proves so deadly in patients with severe COVID-19. Another possibility is that infections with other diseases results in cross-protective immunity.

“However, it is also important to know how COVID-19 has affected the transmission and severity of these endemic diseases, such as malaria,” said Dinglasan.

A network in Africa

Dinglasan has several long-term malaria studies ongoing in urban and rural settings in the Democratic Republic of Congo and has connections at a network of clinics and hospitals that will be useful in the new research. Through long-standing personal relationships in Nigeria, the project will leverage existing surveillance networks there, too.

“Nigeria has a system of clinics and hospitals already in place to monitor infectious diseases across urban and rural settings as well,” said Dinglasan. “The ability to mirror surveillance approaches in two countries will help us learn about differences in diverse infectious disease patterns between rural villages and denser urban areas.”

Also collaborating on the project are scientists at the African Center of Excellence for Genomics of Infectious Diseases in Nigeria; the Kinshasa School of Public Health and the National Institute of Biomedical Research in the Democratic Republic of Congo; the University of North Carolina at Chapel Hill; the University of Massachusetts; and Mass Biologics, a Massachusetts biotech company.

Co-investigator Christian Happi, a professor at Redeemer’s University in Nigeria, is an expert in applying genomic technologies to infectious disease outbreaks. Happi’s prior work contributed to containing Ebola virus by performing in-country early diagnostic testing and the discovery of new circulating strains of SARS-CoV-2.

“This study provides a unique opportunity to understand the community spread of COVID-19 in Nigeria, therefore providing information that will be very useful to the Nigeria Center for Disease Control for targeted interventions,” said Happi. “The study results will enable scientists to characterize the different epidemiological presentations of COVID-19 in two populous African countries and relate the data to different public health interventions in Nigeria and the Democratic Republic of Congo.”

Patterns of infection

Researchers will collect blood samples from 1,500 participants per country to test for markers of past and current SARS-CoV-2 infection and other endemic parasites or viruses. The samples will be collected four times over several years to track participants’ health and disease risk.

“We will follow the experiences of people who live in villages versus towns versus cities,” said Dinglasan.

Team members will also visit villages to perform household surveys and map geographic and climatic factors that serve as proxies for the effects of climate change on disease exposure and burden. Co-investigator Jain, and his lab members, have engineered CRISPR-based tests for detecting genetic markers of SARS-CoV-2 in saliva. These simple and rapid tests will be used in the field for detecting genetic variants of SARS-CoV-2 and will also be used to monitor for other pathogens. Data from urban and rural settings will be compared to look for patterns that might influence susceptibility to severe COVID-19.

“This project gets at some big questions about what makes us susceptible to infectious diseases,” said Dinglasan. “If we can learn what can protect us as a species, we could potentially be better prepared for the next pandemic.”

Written by: DeLene Beeland