Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Late Miocene ostracod assemblages from eastern Mediterranean coral reef complexes (central Crete, Greece)

Ostracods from ten Late Miocene coral reef complexes built by Siderastrea, Tarbellastrea and Porites, cropping out in the Messara Plain (southern Iraklion basin, central Crete), have been investigated and five assemblages have been recognised, which point to different marine environments: (1) assemblage from the basal sandy silts, dominated by very shallow inner-infralittoral species, such as Cyamocytheridea meniscus, Cyamocytheridea obstipa, Cyamocytheridea dertonensis, Cytheretta semiornata and Nonurocythereis seminulum; (2) assemblage from the coral reef complexes within which Grinioneis haidingeri, Aurila cicatricosa, Cimbaurila diecii, Tenedocythere cruciata, Pokornyella italica and Callistocythere quadrangula are dominant and point to a stable inner-infralittoral environment characterised by warm, quiet and well-oxygenated waters; (3) assemblage from the silts intercalated among the coral reef complexes, mainly characterised by Neomonoceratina laskarevi, Cytheridea acuminata, Phlyctenophora farkasi and Aurila albicans together with Callistocythere spp., Xestoleberis communis and Xestoleberis dispar, which points to a very shallow marine environment rich in aquatic vegetation; (4) assemblage from the upper silts, which records the absolute dominance of Xestoleberis species, reflecting a very shallow and highly-vegetated environment and (5) assemblage from the uppermost silty clays, dominated by Hemicytherura defiorei, Xestoleberis spp. and Palmoconcha dertobrevis, accompanied by Acanthocythereis hystrix, Cytherella scutulum, Bairdoppilata conformis, Semicytherura spp., Krithe sp., Cytheropteron alatum, Bythocypris sp. and Pseudocythere caudata, which suggest deeper marine environments probably located in the outer infralittoral/inner-circalittoral zones. The studied section has been dated by means of calcareous nannoplankton to be not younger than Zone MNN9 (Early Tortonian), which is the biostratigraphical datum recorded in the fine-grained deposits that overlie the coral reef complexes. An age not older than Tortonian can be inferred by the stratigraphical distribution of the recognized ostracods. Thus, the coral reef complexes have been tentatively referred to the Early Tortonian