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BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1β have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1β. Following IVIG treatment, activated IL-1β+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer 'growing seasons'. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass. National Science Foundation (NSF DEB) [1431428, 1136637]; Washington State University; Russian Science Foundation [14-14-00400]; Ministry of education and science of Russia Gos-Zasanie project [1354-2014/51]; Natural Environment Research Council [NE/J00829X/1, 1230750, NE/G019622/1, NE/J010227/1] Funding was provided by the National Science Foundation (NSF DEB #1431428; NSF DEB #1136637) and Washington State University. M. Timofeyev and E. Silow were partially supported by Russian Science Foundation project No 14-14-00400 and Ministry of education and science of Russia Gos-Zasanie project No 1354-2014/51. We are grateful to Marianne Moore, Deniz Ozkundakci, Chris Polashenski and Paula Kankaala for discussions that greatly improved this work. We also gratefully acknowledge the following individuals for contributing to this project: John Anderson, Jill Baron, Rick Bourbonniere, Sandra Brovold, Lluis Camarero, Sudeep Chandra, Jim Cotner, Laura Forsstom, Guillaume Grosbois, Chris Harrod, Klaus D. Joehnk, T.Y. Kim, Daniel Langenhaun, Reet Laugaste, Suzanne McGowan, Virginia Panizzo, Giampaolo Rossetti, R.E.H. Smith, Sarah Spaulding, Helen Tammert, Steve Thackeray, Kyle Zimmer, Priit Zingel and two anonymous reviewers. Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the US Government.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer "growing seasons." We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 42.8% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume, and 34.4% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time-series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.