Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Kinetics of 1,6-hydrogen migration in alkyl radical reaction class

The kinetics of the 1,6-intramolecular hydrogen migration in the alkyl radical reaction class has been studied using the reaction class transition state theory (RC-TST) combined with the linear energy relationship (LER) and the barrier height grouping (BHG) approach. The RC-TST/LER, where only reaction energy is needed, and RC-TST/BHG, where no other information is needed, are found to be promising methods for predicting rate constants for any reaction in the 1,6-intramolecular H migration in alkyl radicals reaction class. Direct comparison with available experimental data indicates that the RC-TST/LER, where only reaction energy is needed, can predict rate constants for any reaction in this reaction class with satisfactory accuracy

Late quaternary sea-ice and sedimentary redox conditions in the eastern Bering Sea – Implications for ventilation of the mid-depth North Pacific and an Atlantic-Pacific seesaw mechanism

On glacial-interglacial and millennial timescales, sea ice is an important player in the circulation and primary productivity of high latitude oceans, affecting regional and global biogeochemical cycling. In the modern North Pacific, brine rejection during sea-ice freezing in the Sea of Okhotsk drives the formation of North Pacific Intermediate Water (NPIW) that ventilates the North Pacific Ocean at 300 m to 1000 m water depth. Glacial intervals of the late Quaternary, however, experienced a deepening of glacial NPIW to at least 2000 m, with the strongest ventilation observed during cold stadial conditions of the last deglaciation. However, the origin of the shifts in NPIW ventilation is poorly understood. Numerical simulations suggest an atmospheric teleconnection between the North Atlantic and the North Pacific, in response to a slowdown or shutdown of the Atlantic meridional overturning circulation. This leads to a build-up of salinity in the North Pacific surface ocean, triggering deep ventilation. Alternatively, increased sea-ice formation in the North Pacific and its marginal seas may have caused strengthened overturning in response to enhanced brine rejection. Here we use a multi-proxy approach to explore sea-ice dynamics, sedimentary redox chemistry, and benthic ecology at Integrated Ocean Drilling Program Site U1343 in the eastern Bering Sea across the last 40 ka. Our results suggest that brine rejection from enhanced sea-ice formation during early Heinrich Stadial 1 locally weakened the halocline, aiding in the initiation of deep overturning. Additionally, deglacial sea-ice retreat likely contributed to increased primary productivity and expansion of mid-depth hypoxia at Site U1343 during interstadials, confirming a vital role of sea ice in the deglacial North Pacific carbon cycle