Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs, including recently circulating BA.4/BA.5, in both pseudovirus-based and live virus assays, and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

[Use of thromboelastography and thromboelastometry for the rational and opportune transfusion of hemoderivatives in obstetric hemorrhage]. / Uso de tromboelastrografía y tromboelastometría para la transfusión racional y oportuna de hemoderivados en hemorragia obstétrica.

Obstetric hemorrhage is the leading cause of maternal mortality, responsible of 143,000 deaths every year. Thromboelastography is a tool that allows measuring the viscoelastic, dynamic and global properties of the blood, offering valuable information of coagulation alterations and help to guide early goal directed transfusional therapy. The purpose of this review is to evaluate the evidence of this tool in obstetric hemorrhage and the management of the associated coagulopathy.