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Little information is available about the nature of the immune response in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. The aim of this study is to define the seroprevalence and the features of the antibody response in children of Southern Switzerland during the different waves of Coronavirus Disease 2019 (COVID-19) pandemic. By analyzing 756 sera collected from children aged 0 to 16 years admitted to the Institute of Pediatrics of Southern Switzerland during the prepandemic period (before March 2020) and the first four pandemic waves (between March 2020 and June 2022), we investigated binding titers, cross-reactivity, and neutralizing properties of the serum antibodies against SARS-CoV-2 variants. Seroprevalence varied from 6% during the first wave to 14% and 17% during the second and third waves, respectively, peaking at 39% during the fourth wave. The 96 seropositive cases were mostly asymptomatic (42.7%) or showed mild (20.8%) to moderate (32.3%) symptoms. Moderate symptoms and close contact with COVID-19-positive individuals were associated with a higher infection risk (P < 0.001). The antibody response was mainly driven by IgG directed to the receptor-binding domain (RBD) of Wuhan-1 SARS-CoV-2 Spike (S). Children infected in the first three waves produced antibodies with up to 11-fold and 5.5-fold reduction in binding and neutralizing titers, respectively, against different SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, BA.2, and BA.5. Such reductions were less pronounced in children infected during the fourth wave, who showed the highest frequency and titers of neutralizing antibodies against the same variants. Compared to infection, vaccination with a Wuhan-1-based messenger RNA (mRNA) vaccine induced higher and heterogenous levels of antibodies cross-reacting to the different SARS-CoV-2 variants analyzed.   Conclusions: Despite the high burden of COVID-19 in Southern Switzerland, we observed an initial low seroprevalence of SARS-CoV-2 in children, which increased in the later waves. The antibody response was poor in the first three waves and improved in the fourth wave, when children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants. What is Known: • Children were marginally affected by the initial SARS-CoV-2 variants. • The number of infected and hospitalized children increased after the appearance of the Omicron variants. What is New: • Seroprevalence of SARS-CoV-2 in children of Southern Switzerland increased overtime. • Children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants in the fourth wave compared to children infected in the first three waves., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Case summary Two 18-day-old domestic shorthair kittens presented with dyspnoea, mild cyanosis, heart murmur, lung pattern, abnormal crawling and a marked dorsoventral flattening of the thorax. Deformity of the thoracic wall without pectus excavatum was diagnosed. Cardboard corsets tailored to each kitten were applied. This gave immediate respiratory relief, easing distress and pain. After 10 days, clinical and radiographic monitoring revealed normalisation of the shape of the chest wall with an improvement in general condition. At 6 months of age, clinical examination showed normal growth and development of both kittens, with a normal thoracic profile and shape also seen on radiographs. Relevance and novel information Data about flat-chested kitten syndrome and its aetiopathogenesis, treatment and outcome are scarce, but there is significant experience among breeders that is shared through online communities. High mortality rates are reported. The use of a cardboard splint appears to be novel in the published literature; in this case report, it proved to be a rapid and easy solution. For this reason, cardboard splints could be considered as a first approach for the clinical management of flat-chested kitten syndrome., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Artificial intelligence (AI), using deep learning (DL) systems, can be utilised to detect radiological changes of various pulmonary diseases. Settings with a high burden of tuberculosis (TB) and people living with HIV can potentially benefit from the use of AI to augment resource-constrained healthcare systems., Objective: To assess the utility of qXR software (AI) in detecting radiological changes compatible with lung cancer or pulmonary TB (PTB)., Methods: We performed an observational study in a tertiary institution that serves a population with a high burden of lung cancer and PTB. In total, 382 chest radiographs that had a confirmed diagnosis were assessed: 127 with lung cancer, 144 with PTB and 111 normal. These chest radiographs were de-identified and randomly uploaded by a blinded investigator into qXR software. The output was generated as probability scores from predefined threshold values., Results: The overall sensitivity of the qXR in detecting lung cancer was 84% (95% confidence interval (CI) 80 - 87%), specificity 91% (95% CI 84 - 96%) and positive predictive value of 97% (95% CI 95 - 99%). For PTB, it had a sensitivity of 90% (95% CI 87 - 93%) and specificity of 79% (95% CI 73 - 84%) and negative predictive value of 85% (95% CI 79 - 91%)., Conclusion: The qXR software was sensitive and specific in categorising chest radiographs as consistent with lung cancer or TB, and can potentially aid in the earlier detection and management of these diseases.

Introduction: Pipeline programs can help increase diversity in health care by engaging underrepresented minority groups to pursue higher education and training in medical fields. Here we describe the implementation of Health Career Collaborative, a pipeline program designed to connect high school students with health care professionals, and the transition to remote delivery of the curriculum., Methods: This study is a retrospective, descriptive observational study where the baseline characteristics of participating students were evaluated via preparticipation surveys. This study took place in a community with an area deprivation index of 6 at a high school in southern California in conjunction with an academic medical center and level I trauma center. Due to the coronavirus disease 2019 pandemic, the program transitioned to a virtual setting in the second half of the academic year., Results: A total of 37 high school student participants enrolled in the 2019-2020 Health Career Collaborative program, with over 97% identifying as Hispanic, 89% female, and 92% between the ages of 15 and 17. Ninety-five percent of students indicated plans to graduate from high school and attend college, and 89% agreed with having a mentor to help plan for their future. While high school students had exposure to several health topics prior to the program, students reported a preference to learn about health topics from doctors compared to other sources., Conclusions: An online platform helped facilitate more interaction with health care professionals and could improve feasibility of implementing pipeline programs because physical space and transportation are not required., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

By analogy with the construction of the Furstenberg boundary, the Stone–Čech boundary of |$\textrm {SL}(3,\mathbb {Z})$| is a fibered space over products of projective matrices. The proximal behaviour on this space is exploited to show that the preimages of certain sequences have accumulation points that belong to specific regions, defined in terms of flags. We show that the |$\textrm {SL}(3,\mathbb {Z})\times \textrm {SL}(3,\mathbb {Z})$| -quasi-invariant Radon measures supported on these regions are tempered. Thus, every quasi-invariant Radon boundary measure for |$\textrm {SL}(3,\mathbb {Z})$| is an orthogonal sum of a tempered measure and a measure having matrix coefficients belonging to a certain ideal |$c^{\prime}_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠ , slightly larger than |$c_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠. Hence, the left–right representation of |$C^*(\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| in the Calkin algebra of |$\textrm {SL}(3,\mathbb {Z})$| factors through |$C^*_{c^{\prime}_0} (\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| and the centralizer of every infinite subgroup of |$\textrm {SL}(3,\mathbb {Z})$| is amenable. [ABSTRACT FROM AUTHOR]

The management of unowned cats is an emerging problem, with public institutions and citizens' concerns regarding their care and arrangement. Little is known regarding the outcome of traumatic orthopedic injuries in these patients. Indeed, complete functional recovery (CFR) should be the goal of treatment for return to their original location or adoption. The aim was to identify clinical factors influencing CFR in traumatized unowned cats with orthopedic lesions. This category of cats referred by the veterinary public service over three years was enrolled. Various clinical variables were retrospectively collected from the medical records and evaluated by nominal logistic analysis. Forty-eight unowned cats were enrolled, with a median estimated age of 24 (1-180) months and a body weight of 3 (0.7-5) kg. Thirty-four (71%) patients reached CFR. Estimated age, body weight, time from trauma to therapeutic intervention, spine involvement, presence of comorbidities, hospitalization time, and the radiographic score results were significantly associated with CFR. A longer time to therapeutic intervention seemed to be associated with a better outcome. Probably, cats severely traumatized did not live long enough to be evaluated and treated. Lighter cats experienced more severe consequences following blunt trauma. Younger and lighter cats bore a higher risk of panleukopenia-related death.

A 2-year-old female American Akita was referred for CT of the pelvis and hindlimbs due to a left hindlimb lameness after a left total hip replacement. Referral radiographs and CT images demonstrated amorphous soft-tissue and mineral opacities surrounding the proximal femur and the prosthetic stem, consistent with the "cloud sign" reported as a characteristic of metallosis in humans. Dorsomedial displacement of the prosthetic head, multiple foci of geographic osteolysis alongside the "cloud sign", presumed pseudotumor lesions, and medial iliac lymphadenopathy were also identified with CT. Metallosis was confirmed based on ultrasound-guided cytology, revision surgery, and histopathology., (© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein., Methods: Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model., Results: We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance. IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways. Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis., Conclusion: Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting., (© 2023. The Author(s).)

A 6-mo-old, intact male, domestic shorthair cat was referred with a history of poor growth, reluctance to move, and deformation of the nasal profile. The kitten had been fed a diet composed almost exclusively of a complementary pet food and tuna, which was similar to an all-meat diet. We detected osteopenia and hypocalcemia associated with severe parathyroid hormone (PTH) and calcitriol increases; we measured PTH concentrations with an immunoenzymatic method that has been validated in cats. Dietary correction, consisting of a complete and balanced wet pet food formulated for growth, resulted in normalization of calcium and PTH concentrations within 2 mo.

The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine. Most monoclonal antibodies that are directed against the receptor-binding motif lost in vitro neutralizing activity against Omicron, with only 3 out of 29 monoclonal antibodies retaining unaltered potency, including the ACE2-mimicking S2K146 antibody 1 . Furthermore, a fraction of broadly neutralizing sarbecovirus monoclonal antibodies neutralized Omicron through recognition of antigenic sites outside the receptor-binding motif, including sotrovimab 2 , S2X259 3 and S2H97 4 . The magnitude of Omicron-mediated immune evasion marks a major antigenic shift in SARS-CoV-2. Broadly neutralizing monoclonal antibodies that recognize RBD epitopes that are conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity, and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month time frame. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both prefusion and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sublineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants., Competing Interests: R.M., J.B., C.S.-F., I.B., F.M., K.C., N.S., G.L., C.S., E.C., E.A.D.J., J.R.D., N.C., C.H.-D., A.T., A.A., H.W.V., A.L., D.C., and L.Pi. are or were employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. C.G. is an external scientific consultant to Humabs BioMed SA. The other authors declare no competing interests., (© 2022 The Authors.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant-neutralizing antibody that is a strong candidate for clinical development.

Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD), with radiographs frequently used to screen for evidence of left-sided cardiomegaly secondary to MMVD. Vertebral heart size (VHS), vertebral left atrial size (VLAS), modified VLAS (M-VLAS), and radiographic left atrial dimension (RLAD) are reported as objective measurements of global heart size and left atrial size. Normal VHS in CKCS (10.6 ± 0.5) is reportedly higher than the non-breed-specific value (9.7±0.5). Breed-specific VLAS, M-VLAS, and RLAD cut-offs have not been reported in CKCS. The aim of this prospective reference interval study was to describe the VHS, VLAS, M-VLAS, and RLAD values for 30 clinically healthy adult CKCS. Inclusion criteria were unremarkable physical examination, normal echocardiography, and thoracic radiographs without malposition/abnormalities. There were 22 female and eight male dogs. Ages ranged from 1 to 6 years. The VHS mean value in our sample was 10.08 ± 0.56 (95% range, 9.87-10.29). This was significantly greater than a previously published general canine reference value of 9.7 ± 0.5 and significantly less than a previously published CKCS breed-specific value of 10.6 ± 0.5 (P < 0.01). Mean VLAS, M-VLAS, and the RLAD values in our study were 1.79 ± 0.3 (95% range, 1.68-1.9), 2.23 ± 0.44 (95% range, 2.06-2.39), and 1.2 ± 0.34 (95% range, 1.07-1.33), respectively. These were significantly less than previously published reference interval values (P < 0.001). The VHS, M-VLAS, and the RLAD were not affected by sex, body weight, or BCS; whereas the VLAS was moderately affected by body weight. Findings from this study can be used as background for future thoracic radiographic assessments in CKCS., (© 2021 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.B., C.S.-F., F.M., C.S., M.Me., E.A.D.J., N.C., E.C., D.C. A.L., and L.Pi. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. R.K.G. has received consulting fees from Johnson and Johnson and GlaxoSmithKline for educational activities. The other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha) 1 . In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era., (© 2021. The Author(s).)

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape 1-3 , have activity against diverse sarbecoviruses 4-7 , and be highly protective through viral neutralization 8-11 and effector functions 12,13 . Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E12 8 ) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies., (Copyright © 2021, American Association for the Advancement of Science.)

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics., Competing Interests: Declaration of interests L.E.R., R. Spreafico, J.A.W., L.P., J.D., N.C., M.M., A.D.M., J.B., D.P., K.C., F.Z., S.J., M.B., M.P., E.C., J.D.I., H.W.V., A.T., D.C., and G.S. are or were employees of Vir Biotechnology and may hold shares in Vir Biotechnology. C.G. is an external scientific advisor for Humabs BioMed SA. J. Nix and T.I.C. are consultants with Vir Biotechnology. M.G.S. declares interest in Integrum Scientific, Greensboro, NC, outside the scope of this work. J.D.C. is a current member of the Scientific Advisory Board of OpenEye Scientific Software and is a scientific consultant to Foresite Labs. The Chodera laboratory (I.Z., W.G.G., and J.D.C.) receives or has received funding from multiple sources, including the NIH, the National Science Foundation, the Parker Institute for Cancer Immunotherapy, Relay Therapeutics, Entasis Therapeutics, Silicon Therapeutics, EMD Serono (Merck KGaA), AstraZeneca, Vir Biotechnology, XtalPi, the Molecular Sciences Software Institute, the Starr Cancer Consortium, the Open Force Field Consortium, Cycle for Survival, a Louis V. Gerstner Young Investigator Award, and the Sloan Kettering Institute. A complete funding history for the Chodera lab can be found at https://www.choderalab.org/funding. The other authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The literature refers that Angiostrongylus vasorum should always be considered in the differential diagnosis of respiratory diseases in captive red panda (Ailurus fulgens) from endemic areas, and the importance of undertaking a careful diagnostic process and timely medical treatment are crucial when the disease is suspected. The authors think that the description of this clinical case can help other colleagues in the deworming, clinical and anesthesiologic management of infected subjects., Methods: A red panda was referred to the Veterinary Teaching Hospital of the University of Milan in Lodi, due to a diagnosis of A. vasorum formulated in May 2015. The diagnosis was made after the detection of both first-stage larvae by Baermann technique and antigens by serological rapid in-clinic assay. In addition, haemochromocytometric and blood chemistry tests, echocardiography and a CT examination were carried out., Results: The subject was successfully treated by oral administration of milbemycin oxime and praziquantel (Milbemax, Novartis, Italy), respectively, at the weekly dose of 12.5 mg/subject and 125 mg/subject for three consecutive weeks, alternated with 20 days of suspension. Treatment continued with the same scheme until clinical examination carried out in Lodi in December 2018., Conclusion: The follow-up of the described clinical case demonstrates how appropriate management of the infection and the subsequent prophylaxis can correctly eliminate the parasite, thus avoiding the spread of the nematode and the onset of severe and lethal lung forms as described in the literature.