TY  - JOUR
N2  - SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fc? receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.
SN  - 0028-0836
SP  - 576
AV  - public
UR  - https://doi.org/10.1038/s41586-022-04702-4
ID  - discovery10149998
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
JF  - Nature
PB  - NATURE PORTFOLIO
KW  - Antimicrobial responses
KW  -  Immune cell death
KW  -  Monocytes and macrophages
KW  -  SARS-CoV-2
A1  - Junqueira, Caroline
A1  - Crespo, Ângela
A1  - Ranjbar, Shahin
A1  - De Lacerda, Luna B
A1  - Lewandrowski, Mercedes
A1  - Ingber, Jacob
A1  - Parry, Blair
A1  - Ravid, Sagi
A1  - Clark, Sarah
A1  - Schrimpf, Marie Rose
A1  - Ho, Felicia
A1  - Beakes, Caroline
A1  - Margolin, Justin
A1  - Russell, Nicole
A1  - Kays, Kyle
A1  - Boucau, Julie
A1  - Das Adhikari, Upasana
A1  - Vora, Setu M
A1  - Leger, Valerie
A1  - Gehrke, Lee
A1  - Henderson, Lauren
A1  - Janssen, Erin
A1  - Kwon, Douglas
A1  - Sander, Chris
A1  - Abraham, Jonathan
A1  - Goldberg, Marcia B
A1  - Wu, Hao
A1  - Mehta, Gautam
A1  - Bell, Steven
A1  - Goldfeld, Anne E
A1  - Filbin, Michael R
A1  - Lieberman, Judy
EP  - 584
Y1  - 2022/06/16/
TI  - Fc?R-mediated SARS-CoV-2 infection of monocytes activates inflammation
VL  - 606
ER  -