IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM⁺ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.     

Ultrasound guidance for femoral venous access in patients undergoing pulmonary vein isolation: A quasi-randomized study

Introduction

Routine ultrasound (US) guidance for femoral venous access to decrease vascular complications of atrial fibrillation (AF) ablation procedures has been advocated. However, the benefit has not been unequivocally demonstrated by randomized-trial data.

Methods

Consecutive patients undergoing pulmonary vein isolation (PVI) on uninterrupted anticoagulant treatment were included. A quasi-random allocation to either US-guided or conventional puncture group was based on which of the two procedure rooms the patient was scheduled in, with only one of the rooms equipped with a US machine including a vascular transducer. The same four novice operators in rotation, with no relevant previous experience in US-guided vascular access performed venous punctures in both rooms. Major and minor vascular complications and the rate of prolonged hospitalization were compared. Major vascular complication was defined as groin hematoma, arteriovenous fistula, or pseudoaneurysm. Hematoma was considered as a major vascular complication if it met type 2 or higher Bleeding Academic Research Consortium criteria (requiring nonsurgical, medical intervention by a health care professional; leading to hospitalization or increased level of care, or prompting evacuation).

Results

Of the 457 patients 199 were allocated to the US-guided puncture group, while the conventional, palpation-based approach was performed in 258 cases. Compared with the conventional technique, US guidance reduced the rate of any vascular complication (11.63% vs. 2.01%, p < .0001), including both major (4.26% vs. 1.01%, p = .038) and minor (7.36% vs. 1.01%, p = .001) vascular complications. In addition, the rate of prolonged hospitalization was lower in the US-guided puncture group (5.04% vs. 1.01%, p = .032).

Conclusion

The use of US for femoral vein puncture in patients undergoing PVI decreased the rate of both major and minor vascular complications. This quasi-randomized comparison strongly supports adapting routine use of US for AF ablation procedures.