Thread by @TsangLab

Sharing our latest paper in @Nature (nature.com/articles/s4158…), in which we ask whether non-hospitalized #COVID19 could change the status of the #immune system in ways that then impact future responses to a distinct perturbation, the #influenza #vaccine, long after recovery👇

We employ systems #immunology and #SingleCell multiomic approaches. Check out the reusable multimodal single cell, transcriptomics, circulating proteins and other data at: ncbi.nlm.nih.gov/geo/query/acc.… and doi.org/10.5281/zenodo…

This work, led by Rachel Sparks, William Lau, and Can Liu, took advantage of a unique opportunity and unprecedented epidemiological environment during the early fall of 2020, months after the first wave of COVID-19, when those with mild COVID-19 had recovered clinically, 👇

but before they could be reinfected by #SARSCoV2 or receive COVID-19 #vaccination (which was not available until late 2020); additionally, the prevalence of other respiratory infections was extremely low during this time. 👇

This allowed us to utilize mild COVID-19 as a natural perturbation followed by the timed, well-characterized influenza vaccine as the second, timed perturbation (distinct from the first, SARS-CoV-2 infection) to challenge the human #immune system and monitor its responses. 👇

To our surprise, we found that recovered males mounted a more robust response to the vaccine, generating more antibodies due to a stronger initial inflammatory response to the vaccine. 👇

We were surprised because in general, healthy females tend to mount stronger inflammatory responses to immune perturbations (and are more prone to autoimmunity.) So mild COVID-19 can "flip the immune system", so to speak. 👇

We traced this more robust response in recovered males to altered baseline immune status, including cells that resembled “virtual memory” T cells that can respond rapidly to inflammatory molecules the body makes in response to vaccination and infection. 👇

In our case, these T cells in males responded more strongly to IL-15, which was also transcriptionally elevated in monocytes in COVID-19 recovered males one day after flu vaccination. 👇

A motivation of this study was to ask how baseline immune states are shaped and established. Our findings indicate that past infectious exposures can leave the immune system in altered states that can then impact responses to a perturbation distinct from the prior encounter👇

These findings provide hints on how baseline immune states are established in humans and why they can be predictive of immune responses to different perturbations in antigen agnostic ways (eg see: nature.com/articles/s4159…, sciencedirect.com/science/articl…) 👇

I wanted to especially thank Rachel and her team, who conducted this heroic human study under extremely challenging situations - with locked downs and difficult access to the @NIHClinicalCntr during the early pandemic, and very limited staff 👏👇

Congratulations to Rachel, William, Can, and all co-authors! Thanks to the funding and support of @NIAIDNews, @NIH, @IRPatNIH.