August 3, 2020

Newly launched COVID MITS study aims to improve understanding of COVID-19 immunopathogenesis in Malawi

Dr. Donna Denno, Professor of Pediatrics and Global Health and the Associate Director of Pediatrics for Global WACh, is a co-investigator of a new study funded by the Bill & Melinda Gates Foundation launching in August 2020.  The study titled “MITS for lung pathology and immune response in fatal COVID-19 in Malawi (MITS COVID)” is a one-year project conducted in collaboration with the University of Glasgow, University of Malawi College of Medicine, University of Amsterdam, Liverpool School of Tropical Medicine, Blantyre Malaria Project, and University of Manchester.  Global WACh Research Coordinator, Sarah Lawrence, will also support this investigatory effort.  Building upon the platform established in the Minimally Invasive Tissue Sampling (MITS) in Malawi study (Co-PI: Denno), the team will address knowledge gaps on immune responses against COVID-19 that drive severe diseases in vital organs, particularly in the lung.

Like other respiratory illnesses, COVID-19 causes serious complications in the lungs.  Even with access to optimum healthcare and intensive management strategies, including ventilators in high-income countries, the virus kills 2% of infected individuals through rapidly developing lung disease and severe hypoxia (a lack of oxygen in bodily tissues).  As researchers around the world work overtime to develop a vaccine, treatments are urgently needed as the pandemic spreads in low- and- middle-income countries, including Sub-Saharan Africa, with limited intensive care capacity.  Higher rates of malaria, HIV, and malnutrition may influence pathogenesis and immune responses in these settings.  Findings from the MITS COVID study can help researchers to understand the tissue-specific immune responses that cause severe lung diseases, and to identify treatments to most effectively and safely regulate immune responses to reduce deaths.

This study will build upon the platform established in the MITS in Malawi study, a sub-study of the Childhood Acute Illness and Nutrition (CHAIN) Network to better identify cause of death among acutely ill or undernourished children.  The MITS COVID funding will allow the team to perform MITS in Malawian patients with fatal COVID-19, fatal non-COVID lower respiratory infection, and in patients with infectious non-lung related causes of death and apply high dimensional approaches to study the immunopathogenesis of severe COVID-19.  The team will use cutting-edge techniques, including cytometry (used to determine properties of cells) and gene sequencing, to examine specimens and describe the changing anatomy of tissue-specific immune responses.

Improved understanding of the immunopathogenesis of COVID-19 in Malawi has the potential to inform future therapeutic interventions to improve outcomes for patients with severe COVID-19 infections in settings where access to intensive care is limited and the burden of co-infections such as HIV and malaria may influence immune response, including among women, adolescents, and children.