Research suggests malaria exposure could reduce COVID-19 severity

New research from Uganda and Mali suggests malaria exposure might lower the incidence of severe disease, hospitalization, and death for people exposed to SARS-CoV-2, the virus that causes COVID-19.

The research findings, presented at the American Society of Tropical Medicine and Hygiene’s annual meeting last week, found low levels of severe COVID-19 symptoms among people exposed to SARS-CoV-2 in areas with high malaria burdens, leading researchers to hypothesize that previous malaria exposure could offer its survivors a shield against COVID-19.

Severe cases of COVID-19 are often associated with a surge of proteins called cytokines that cause an inflammatory response and tissue damage. Researchers in Uganda found that COVID-19 patients with a history of malaria infections, as measured by antigen levels in the body, had lower levels of cytokines.

“All of the patients who were categorized as having a high exposure to malaria in the past, had lower levels of the cytokines, across the board, for the different cytokines we measured, in comparison to those who had low previous exposure to malaria,” Dr. Jane Achan, senior research advisor at the Malaria Consortium, a United Kingdom-based non-governmental organization, and a co-author of the study, told Devex.

This was based on a study of nearly 600 COVID-19 patients — looking at whether they were currently or previously exposed to malaria infection. Only 5% of these patients with high levels of previous exposure to malaria developed severe cases of the disease or death, as opposed to about 30% of those with lower levels of previous malaria exposure.

“We went into this project thinking we would see a higher rate of negative outcomes in people with a history of malaria infections because that’s what was seen in patients co-infected with malaria and Ebola,” wrote Achan in a press release. “We were actually quite surprised to see the opposite — that malaria may have a protective effect.”

Achan said this effect, where cytokines don't spike in the bodies of people with previous malaria exposure, has already been documented before the pandemic in older children and adults living in parts of Africa with a high malaria burden.

But she said that previous malaria exposure could also have other impacts on a COVID-19 patient. She said the researchers didn’t measure the change in viral load over time — but previous malaria exposure could also impact viral load, which could impact the severity of symptoms in COVID-19 patients. Other groups are currently investigating this, she said.

Achan told Devex that these findings could influence the development of treatment options for COVID-19.

She said that the next research steps would include looking at this effect in a larger population of people. And there is further work to be done on whether previous exposure to malaria impacts the long-term complications associated with COVID-19.

Another study presented at the meeting found that despite widespread infection of SARS-CoV-2 in Mali, severe disease, hospitalization, and death were rare.

The researchers, from the United States National Institute of Allergy and Infectious Diseases and the Malaria Research Training Center in Bamako, Mali, conducted seroprevalence surveys of over 3,500 people in four communities in Mali’s capital city of Bamako, and its surrounding areas, as well as documenting their symptoms, according to Dr. John Woodford, a malaria researcher at NIAID and co-author of the study. This type of study examines what percentage of a population has antibodies to the virus in their blood over time.

As of January 2021, about 59% of community members had been exposed to the SARS-CoV-2 virus, but this high level of exposure was not accompanied by a large influx of people into health centers. Some of these communities had not reported any COVID-19 cases throughout the pandemic.

The COVID-19 attributable symptoms people reported weren’t substantially higher than the typical rates of illness experienced in the communities. In fact, the number of hospitalizations and deaths we're lower than those for age-adjusted U.S. rates of severe disease — to account for the fact that, like much of the rest of sub-Saharan Africa, the population of Mali is relatively young.

“It's not that we're not seeing any markers of disease severity, it is that the rates of reporting of hospitalizations, symptomatic illness, and death are lower than would be expected. Sometimes, several fold lower,” Woodford said.

Wood said they found that these communities had high rates of exposure to other coronaviruses previously, but no evidence that antibodies from other coronaviruses provided protection against SARS-CoV-2. Because of this, key hypotheses include low rates of co-morbidities in the community — or high exposure to other infections, particularly malaria, which has been previously linked to protection against other severe viral infections.

Mali has a high malaria burden. Woodford said that about 35% of the population in one of the rural villages was diagnosed with malaria over the study period. One hypothesis is that the findings could suggest that these individuals’ immune systems have been trained by recurrent infection from malaria to not overreact with inflammation when it encounters SARS-CoV-2.

Woodford said “it starts to paint a picture.”

The researchers are interested in further testing around this, and will release data from August and September in the near future, but it's very hard to test, he said, because “getting direct evidence to show that malaria infection reduces severe illness, and understanding how, will be challenging.”

And ultimately, these findings raise questions about how to best allocate limited health resources, to balance the COVID-19 response with other deadly illnesses such as malaria, Woodford said.

“We really need to understand the effects of the pandemic, locally, in Mali and in West Africa, in order to help prioritize the allocation of public health resources. Countries might not be using the most effective public health interventions,” he said. Mali’s Ministry of Health made an early decision to continue malaria program activities in 2020.

“​​In light of our findings, this was a good decision,” Woodford said. “The COVID pandemic has had a lesser impact than expected, while malaria continues to have a marked seasonal burden on the population.”