COVID-19 and Early Post-Primary TB: Commonalities of Pathobiology in Pneumonitis and Therapies

Concurrent infection with COVID-19 and M. tuberculosis has been reported to be more severe than either alone, resulting in increased mortality. Our objective was to define the shared pathobiology of COVID-19 and the developmental stage of TB in the lung and explore adjunctive therapies to treat such commonalities.

Since morphoproteomics combines the disciplines of histopathology, molecular biology and protein chemistry to paint a portrait of the protein circuitry in diseased cells for the purpose of uncovering targets amenable to specific intervention [1], we used morphoproteomic analyses to study lung tissues of patients with early post-primary tuberculosis or COVID-19 infection.

These studies showed co-localization of the COVID-19 virus and M. tuberculosis antigens with cyclo-oxygenase-2 and fatty acid synthase in the reactive alveolar pneumocytes and with programmed death-ligand 1 expression on the alveolar interstitium and alveolar pneumocytes. This was associated with accumulation of pro-infectious M2 polarized macrophages in the alveolar spaces.

The commonalities in these pathways suggest that they might be susceptible to adjunctive therapies with metformin and vitamin D3. This is supported by published studies that metformin and vitamin D3 could reduce the severity of both COVID-19 and early post-primary TB infections.