High exposure to malaria can modulate immune response to COVID-19 resulting in less severe outcomes, study shows

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The results of ground-breaking research conducted by Malaria Consortium show that low previous malaria exposure is associated with more severe symptoms of COVID-19 and adverse outcomes compared with high exposure to malaria. Patients co-infected with malaria and COVID-19 tend to have a higher frequency of confusion and vomiting but co-infection was not detrimental to a patient’s outcome. The results were recently published in preprint in The Lancet.  

Malaria causes significant morbidity and mortality with an estimated 229 million cases and 409,000 deaths reported globally in 2019 alone, over 90 percent of these in sub-Saharan Africa. The potential implications of any clinical interactions between COVID-19 and malaria infection is therefore a major public health concern in Africa, where the chances of co-infection is relatively high. The objective of the study was to better characterise COVID-19 cases in a high malaria burden setting and to determine the prevalence and describe the clinical consequences of SARS-CoV-2 and malaria co-infection.

“This is the first study to describe in detail what is potentially happening in terms of clinical interactions between malaria and COVID-19,” said Jane Achan, Senior Research Adviser at Malaria Consortium and co-author of this study. “Given the prevalence of malaria in sub-Saharan Africa, understanding the pathology of what this means for patient outcomes is of huge importance. Modelling done at the start of the pandemic predicted the potential consequences of COVID-19 on malaria deaths due to interrupted interventions, but little is known about the impact of co-infection on morbidity and mortality. It was important for us to be able to rapidly respond to a global need and contribute to better understanding of the pathogenesis and relationship between the two diseases.”

The study, conducted between April and October 2020, analysed the results of 597 patients of all ages with a confirmed diagnosis of SARS-CoV-2 at COVID-19 treatment centres in eight tertiary hospitals across North, East, South and North-Western regions of Uganda. To determine the level of malaria exposure in patients, the research measured the level of immune response to components of the malaria parasite (P. falciparum) at time of hospitalisation. A very strong immune response indicates high previous exposure to malaria either recently or over time and low or no evidence of a response indicates low previous exposure to malaria. 

The proportion of patients with low previous exposure to malaria suffering severe or critical COVID-19 was 30.2 percent compared to only 5.4 percent of those with high previous exposure. The impact of low malaria exposure on the severity of COVID-19 remained even in patients without co-morbidities.

“The results suggest that if you’ve had a high previous exposure to malaria, you’re likely to control or manage COVID-19 better. A patient in Uganda with low previous exposure to malaria appears to respond to COVID-19 in a similar way to a patient in Europe, for example, who has never had malaria before. Previous malaria exposure seems to play a role in the manifestation of COVID-19, possibly at an immunological level. The potential correlation between malaria and COVID-19 may contribute to the reasons why the pandemic has not seen the same number of deaths from COVID-19 as was anticipated across Africa.” 

The study also analysed the cytokine profiles of patients - small proteins that help the body’s immune and inflammation responses. Cytokine profiles in COVID-19 patients in low malaria burden settings have been well characterised, however, there has been limited data from high malaria burden settings. Results of this study showed relatively normal cytokine profiles among patients with high previous malaria exposure and those with a current malaria infection, suggesting some immune modulation or protective regulation at the immune system level that prevents severe manifestations of COVID-19.

This published preprint is in the process of being peer-reviewed and the findings should not be used for clinical or public health decision making nor presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. Malaria Consortium is exploring options for further research to better understand the relationship between the two diseases, in particular pooling similar datasets from across Africa to provide a wider and more robust sample and undertaking longer-term follow up of patients to see how interaction impacts on the long-term outcomes of COVID-19 (long-COVID). 

Malaria Consortium would like to take this opportunity to extend our special gratitude to the patients, healthcare workers and laboratory teams involved in the study at all of the COVID-19 treatment centres for their contribution. 

You can read more about the study here.

Keywords: Research