A fungal-induced immune response that mediates resistance against COVID-19.

BACKGROUND

Here, we aim to determine the effect of previous infection with Paracoccidioides brasiliensis (Pb18), a primary human pathogenic fungus, associated with high mortality and morbidity rates, on the outcome of SARS-CoV-2 infection.

METHODS

The K18hACE2 transgenic mice were infected with 1 × 106 yeasts of the Pb18 fungus followed by the infection with 5 × 104 Plaque-Forming Unit (PFU) of the SARS-CoV-2 virus.

RESULTS

The coinfected mice exhibit lower weight loss and mortality compared to mice infected with the virus alone. Moreover, the inflammatory infiltrate and the viral load of lung, heart, spleen, and brain were lower, suggesting that prior infection with the Pb18 leads to increased resistance against the virus infection. In addition, after SARS-CoV-2 infection, a lower frequency of inflammatory monocytes in the lung tissue of mice previously infected with Pb18 was found. We also observed that mice infected only with SARS-CoV-2 had higher expression of pro-inflammatory cytokines and lower frequency of dendritic cells, alveolar and interstitial macrophages and T lymphocytes in lung tissue compared to mice coinfected or infected only with the fungus. The fungus-induced resistance is dependent on the IFN-I signaling pathway, since treatment with antibody against IFNAR impaired animal survival and viral load.

CONCLUSION

This study reveals a distinct outcome compared to what is typically observed in opportunistic fungal coinfections, highlighting the pathways necessary to induce resistance against viral infections.