We are excited to share the first manuscript from the NU SCRIPT study funded by @NIAIDNews on patients with severe pneumonia, including patients with severe COVID-19. https://www.biorxiv.org/content/10.1101/2020.08.05.238188v1

We systematically profiled bronchoalveolar lavage fluid from 86 patients with severe COVID-19 and 252 patients with severe pneumonia caused by other respiratory pathogens. @NHLBI_LUNGDir @NIAIDNews We were studying viral pneumonia before it was cool!

We found that BAL fluid from patients with COVID-19 was enriched for T cells and monocytes without neutrophilia. In comparison to other types of pneumonia, alveolar macrophages from patients with COVID-19 were characterized by an interferon-response gene signature.

Using scRNA-seq, we found a subset of activated resident alveolar macrophages characterized by an IFN-response signature and SARS-CoV-2 transcripts. We did not detect type I IFNs, but found that T cells were the only source of IFNs - specifically IFNγ - in our dataset.

Together, our findings suggest that resident alveolar macrophages (which do not express ACE2) may act as a non-specific reservoir for SARS-CoV-2 and present antigen to cross-reactive T cells (reported earlier by others) and drive local alveolitis.

This work was led by @RoganAGrant, @luisamnMD, and @system001273866 and supported by many members of @NMPulmCritCare and The NU SCRIPT Study. Data, code and interactive tools are available for exploration via the preprint link.