An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2–neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2–transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.     

Virome of Ixodes ricinus,Dermacentor reticulatus,and Haemaphysalis concinna Ticks from Croatia

Tick-borne diseases are a serious threat to both public and veterinary health. In this study, we used high-throughput sequencing to characterize the virome of three tick species implicated in the spread of vector-borne disease throughout Croatia. Ten viruses were identified, including seven potential novel species within the viral families Flaviviridae, Nyamiviridae, Rhabdoviridae, Peribunyaviridae, Phenuiviridae, and Nairoviridae.     

How we make choices and sacrifices in medical education during the COVID-19 pandemic

Abstract

In this commentary, we highlight some of the pressing choices and sacrifices we must make in medical education during the COVID-19 pandemic.     

Clinical Outcomes and Resource Use for Infants With Hypoplastic Left Heart Syndrome During Bidirectional Glenn: Summary From the Joint Council for Congenital Heart Disease National Pediatric Cardiology Quality Improvement Collaborative Registry

The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry captures information on interstage management of infants with hypoplastic left heart syndrome (HLHS). The purpose of this study was to identify interstage risk factors for increased resource use and adverse outcomes during bidirectional Glenn (BDG) hospitalization. All infants in the NPC-QIC registry (31 United States hospitals) undergoing BDG surgery were included (December 2009 to August 2010). Patient demographics, interstage variables, operative procedures, and complications were recorded. Days of hospitalization, ventilation, inotrope use, and complications were surrogates of resource use. Logistic regression analysis determined the associations between predictor variables and resource use. Of 162 infants, 105 (65 %) were males. At BDG, the median age was 155 days (range 78–128), mean weight-for-age z-score was ?1.6 ± 1.1, mean length-for-age z-score was ?1.5 ± 1.7, and mean preoperative oxygen saturation was 78 % ± 7 %. Caloric recommendations were met in 60 % of patients, and 85 % of patients participated in a home-surveillance program. Median days of intubation, inotrope use, and hospitalization were 1, 2, and 7, respectively. There were 4 post-BDG deaths and 55 complications. In multivariate analysis, lower weight-for-age z-score, female sex, and aortic atresia with mitral stenosis were associated with a higher risk of BDG complications. Meeting caloric recommendations before BDG was associated with fewer hospitalization days. Lower weight-for-age z-score was an independent and potentially modifiable risk factor for BDG complications. HLHS infants who met caloric recommendations before BDG had a lower duration of hospitalization at BDG. These data justify targeting nutrition in interstage strategies to improve outcomes and decrease costs for patients with HLHS.     

Complications of combined radical hysterectomy and pelvic radiation

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 48 women treated by radical hysterectomy (RH) and pelvic node dissection (PND) and in 25 women who received 5000–5400 rad of external pelvic radiation (RT) after RH-PND. No major complications developed in the surgery-only group, but the 5-year minor GI complication rate was 4% and the 5-year minor UT complication rate was 10%. In 9 patients receiving RT at 200 rad/day, one major GI complication (13%) and one major UT complication (14%) developed. In 16 patients receiving RT at 180 rad/day only minor GI complications (7%) and minor UT complications (13%) developed. The conclusion is that after RH-PND, adjunctive RT delivered at 180 rad/day through four ports results in acceptable, minimal complications.     

dPQL: a lossless distributed algorithm for generalized linear mixed model with application to privacy-preserving hospital profiling

ObjectiveTo develop a lossless distributed algorithm for generalized linear mixed model (GLMM) with application to privacy-preserving hospital profiling.Materials and MethodsThe GLMM is often fitted to implement hospital profiling, using clinical or administrative claims data. Due to individual patient data (IPD) privacy regulations and the computational complexity of GLMM, a distributed algorithm for hospital profiling is needed. We develop a novel distributed penalized quasi-likelihood (dPQL) algorithm to fit GLMM when only aggregated data, rather than IPD, can be shared across hospitals. We also show that the standardized mortality rates, which are often reported as the results of hospital profiling, can also be calculated distributively without sharing IPD. We demonstrate the applicability of the proposed dPQL algorithm by ranking 929 hospitals for coronavirus disease 2019 (COVID-19) mortality or referral to hospice that have been previously studied.ResultsThe proposed dPQL algorithm is mathematically proven to be lossless, that is, it obtains identical results as if IPD were pooled from all hospitals. In the example of hospital profiling regarding COVID-19 mortality, the dPQL algorithm reached convergence with only 5 iterations, and the estimation of fixed effects, random effects, and mortality rates were identical to that of the PQL from pooled data.ConclusionThe dPQL algorithm is lossless, privacy-preserving and fast-converging for fitting GLMM. It provides an extremely suitable and convenient distributed approach for hospital profiling.     

Preliminary study on the role of the human IZUMO gene in oocyte-spermatozoa fusion failure

We studied the IZUMO gene 9 coding exons sequence in four groups of patients including those with fertilization failure by conventional IVF. We observed in our populations two combinations of four polymorphisms that appeared to be preferentially linked (CGG-CG and TAA-TT) without any significant difference between different genotype repartitions.