SARS-CoV‑2 has caused a pandemic and is respon­si­ble for more than 18 million infec­tions. It is hypoth­e­sized that COVID-19 is the result of killing of infected cells and exces­sive immune activa­tion. To reveal cell types and pathways that are criti­cally involved in viral repli­ca­tion and patho­gen­e­sis, I will use transcrip­tomics and functional studies of genes likely involved in these processes. The results might inform the devel­op­ment of thera­peu­tic strate­gies and the discov­ery of biomarkers.

The severe acute respi­ra­tory syndrome coronavirus‑2 (SARS-CoV‑2) has caused a pandemic and is respon­si­ble for more than 18 million confirmed infec­tions. Based on clini­cal obser­va­tions, it is hypoth­e­sized that the coron­avirus disease 2019 (COVID-19) is the result of virus-mediated killing of infected cells and exces­sive activa­tion of the cytokine responses. However, to this point it is unknown which pathways are involved in the cytol­y­sis, how cytokines are activated, which cells are respon­si­ble for the cytokine produc­tion in patients and which cells become infected or activated.

I will use transcrip­tional profil­ing of infected cells to identify changes induced by the infec­tion to explain neuro­log­i­cal manifes­ta­tions that have been described in patients and to eluci­date the route of infec­tion and the impact of SARS-CoV‑2 on cells of the immune system. To reveal the cellu­lar tropism and the activa­tion pattern of cytokines in each cell popula­tion that might be involved in the patho­gen­e­sis of COVID-19, I will use single-cell RNA sequenc­ing of infected preci­sion-cut lung sections of SARS-CoV‑2 recep­tor trans­genic mice and bronchoalve­o­lar lavage of COVID-19 patients. These studies will be comple­mented by targeted screen­ings. Pathways of relevance will be studied mecha­nis­ti­cally by using a combi­na­tion of virol­ogy, immunol­ogy, cell biology and biochem­istry methods. Pathways identi­fied might serve as targets for therapy or could be used as biomarkers.