Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2.

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

On-pump transapical cardioscopic mitral valve replacement with cardiac arrest: short-term results in a porcine survival model.

OBJECTIVES: Favourable outcomes with mitral annuloplasty have been achieved with transapical cardioscopic (TAC) surgery in a survival animal model. In addition, experimental TAC on a non-survival animal model also showed adequate access to remove the native mitral valve and implant a prosthetic valve, but the surgical procedure took a long time and lacked follow-up data. The goal of this study was to develop a clinically translatable TAC mitral valve replacement (MVR) procedure using technical and instrumental refinements to reduce the surgical time and to evaluate functional recovery and short-term durability using a survival porcine model. We hypothesized that MVR could be achieved with subannular implantation of the bioprosthesis via the TAC approach. METHODS: TAC MVR using the Hancock II™ (Medtronic)® mitral prosthesis was performed in 6 pigs via an incision over the xiphoid process, under cardiopulmonary bypass and cardiac arrest. COR-KNOT® and minimally invasive cardiac surgery instruments were used. Haemodynamics, echocardiography, cardiac computed tomography, ventriculography and electrocardiography were used to evaluate the function of the mitral prosthesis and left ventricle, coronary system and conduction system in the perioperative period and 4 weeks later. RESULTS: A postimplant examination showed that the mitral prosthesis was competent, without a paravalvular leak. The left ventricular ejection fraction was comparable to preoperative values (65.2 ± 4.1 vs 67.2 ± 7.9). The bypass, cross-clamp and implant times were 177.2 ± 44.2 min, 135.3 ± 47.6 min and 94.0 ± 41.2 min, respectively. The prosthesis was in a good position. The apical scar was intact and not aneurysmal 4 weeks after the implant. The valve was properly sutured to the annulus, without a postimplant paravalvular leak. All animals recovered after 1 month of follow-up with preserved ventricular function and normal wall motion. CONCLUSIONS: We successfully managed to replace the mitral valve with a biological prosthesis via the apex with encouraging bypass and cross-clamp times. This technique may provide an alternative for a selected group of patients with diseased mitral valves who have indications for MVR and still in a high-risk redo setting with conventional sternotomy or minimally invasive cardiac surgery-MVR.

Transapical cardioscopic mitral annuloplasty: a short-term survival study in a porcine model.

OBJECTIVES: The transapical approach provides concurrent surgical access to the mitral and the aortic valves, the root of the aorta and the left atrium. We previously showed the feasibility of transapical cardioscopic (TAC) surgery in a non-survival porcine model. However, reproducibility and feasibility of ring implantation using TAC have not been reported. Therefore, in this study, we hypothesized that implantation of a mitral annuloplasty ring can be feasibly and safely carried out endoscopically via the apex of the heart. METHODS: Using a porcine model in a short-term survival study, TAC mitral annuloplasty was performed in 6 pigs via an incision over the xyphoid, under cardiopulmonary bypass and cardiac arrest. A mitral annuloplasty ring was implanted via the apex to a normal mitral annulus, using a customized set of instruments and techniques. Haemodynamics, echocardiography, cardiac computed tomography, ventriculography, electrocardiography and histopathology studies were used to evaluate the function of the mitral valve and the left ventricle, coronary system and conduction system in the perioperative period and 4 weeks later. RESULTS: All 6 animals survived and recovered from the TAC annuloplasty procedure. Postimplantation examination showed that the mitral valve was competent, left ventricular ejection fraction was 63 ± 4%, left ventricular length was 6.2 ± 0.5 cm and left ventricular end-diastolic volume was 80 ± 10 ml, which were comparable to preoperative values. Apart from a dense scar at the apex, no significant injury was noticed on the ventricle, the chordae and the mitral leaflets. The bypass, cross-clamp and implantation times were 181 ± 55 min, 130 ± 37 min and 47 ± 6 min, respectively. CONCLUSIONS: Despite long surgical times due to the initial learning curve, successful execution of mitral ring annuloplasty could be safely achieved using the TAC approach, via a small incision without the involvement of sternum or the right pleural cavity, thereby potentially expanding the indication to patients with high-risk full sternotomy or right thoracotomy.