COVID-19 rapidly increases MDSCs and prolongs innate immune dysfunctions.

We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID-19 induces a rapid, transient upregulation of myeloid-derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID-19 patients.

Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.

Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies. Trial registration: ClinicalTrials.gov NCT00801697, NCT00961883, NCT02207920, NCT00125970, NCT02852005).

[Should we suspect immune deficiency in internal medicine hospitalized patients?] / Quand suspecter une immunodéficience chez le patient hospitalisé en médecine interne?

Although often overlooked immune deficiencies are more common than generally believed. The internist is frequently the first physician to potentially meet affected patients, playing a significant role in detecting these immune deficiencies, whether they are primary (congenital) or secondary (acquired). In both scenarios, early identification and intervention can greatly reduce the morbidity and mortality of these patients. In this article, we review common immune deficits, suggest initial assessments when indicative signs are present, and provide guidance for management.

Les déficits immunitaires, quoique souvent méconnus, sont plus fréquents qu'on ne le pense. L'interniste est fréquemment le premier médecin à entrer en contact avec des patients potentiellement atteints, jouant ainsi un rôle important dans la détection de ces maladies, qu'elles soient primaires (congénitales) ou secondaires (acquises). Dans les deux cas, une identification et une intervention précoces peuvent considérablement réduire la morbidité et la mortalité de ces patients. Dans cet article, nous passons en revue les déficits immuns fréquents, suggérons des bilans initiaux en présence de signes évocateurs et fournissons des orientations pour la prise en charge.

Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.

The relationship between medical students' empathy, mental health, and burnout: A cross-sectional study.

OBJECTIVE: To investigate how medical students' empathy is related to their mental health and burnout. METHODS: This cross-sectional study included 886 medical students from curriculum years 1-6. The cognitive, affective, and behavioural dimensions of empathy were measured with self-report questionnaires and an emotion recognition test. Regressions were used to test the relationship between the empathy dimensions, depressive symptoms, anxiety, and burnout as well as the influence of curriculum year and gender. RESULTS: Cognitive and behavioural empathy were significantly related to less mental health issues and burnout, whereas affective empathy was related to more mental health issues and burnout. Students in later curriculum years reported less mental health issues and burnout than students in earlier years, whereas no systematic difference could be observed for empathy. Female students reported more mental health issues and burnout as well as higher empathy, except for behavioural empathy for which male students scored higher. CONCLUSIONS: The cognitive, affective, and behavioural dimensions of empathy were differently related to the mental health and burnout of medical students. Students presenting mental health issues or burnout might have more difficulty to adapt their behaviour in social situations and keep a certain distance when taking others' perspective.

[PROFILES: typical portrait of the future Swiss doctors]. / PROFILES: portrait-type de nos futurs médecins !

In each professional practice, a greater or lesser part of the activity is devoted to teaching. Indeed, the transmission of the medical knowledge is an essential objective for the training of students and residents, but also an opportunity to adapt one's own practices to the current context, since fast changes are not necessarily easy to follow and assimilate. If the relationship with Medical school is rather straightforward in the university hospitals, it is not always the same for those who are more distant, but whose participation in teaching is desired, and clearly growing. In this way, it is therefore crucial that everyone is informed about recent changes to the undergraduated learning objectives (PROFILES) and the resulting needs for educational reforms for all Medical schools in Switzerland.

Dans chaque pratique professionnelle, une part plus ou moins grande de l'activité est dévolue à l'enseignement. En effet, la transmission de l'art médical représente un objectif essentiel pour la formation des étudiant·e·s et des jeunes collègues, mais aussi une opportunité pour adapter ses pratiques au contexte actuel, car les changements, rapides, ne sont pas forcément faciles à assimiler. Si, dans les hôpitaux universitaires, le contact avec les Facultés de médecine est plutôt aisé, il n'en va pas toujours de même pour ceux qui en sont plus distants, mais dont la participation à l'enseignement est souhaitée et croissante. En ce sens, il apparaît crucial que tou·te·s soient informé·e·s sur les modifications récentes des objectifs d'apprentissage prégradué (PROFILES) et sur les réformes qui en découlent pour les Facultés de médecine en Suisse.

[Racism and the practice of medicine†: elements for a required learning]. / Racisme et pratique de la médecine†: éléments pour un apprentissage nécessaire.

The new catalogue of objectives for medical education at Swiss universities (PROFILES) underlines the importance of teaching the impact of ethnic, cultural, spiritual and religious differences and the socio-economic determinants of health and illness on health and care. At the same time, the social reality of the moment reminds us that racism is still present in our societies. Therefore, education for medical students is necessary. This should include basic knowledge but also, and above all, an understanding of the underlying mechanisms that will enable them to grasp the notions of prejudice, stereotypes and discrimination. Finally, introspection, the acquisition of cross-cultural skills and cultural humility will help to deal with this other epidemic.

Le nouveau catalogue des objectifs d'enseignement de la médecine dans les universités suisses (PROFILES) souligne l'importance de l'enseignement de l'impact sur la santé et les soins des différences ethniques, culturelles, spirituelles, religieuses, et des déterminants socio-économiques de la santé et de la maladie. Parallèlement, la réalité sociale du moment nous rappelle que le racisme est toujours présent dans nos sociétés. Dès lors, un enseignement aux étudiant·e·s de médecine est nécessaire. Celui-ci devra intégrer des connaissances de base mais aussi et surtout la compréhension des mécanismes sous-jacents qui permettra d'appréhender les notions de préjugés, stéréotypes et discriminations. Enfin, l'introspection, l'acquisition de compétences transculturelles et d'humilité culturelle permettront de faire face à cette autre épidémie.

[Medical students at the bedside of COVID-19 patients†: motivations and challenges]. / Étudiant·e·s en médecine engagé·e·s au chevet des patient·e·s hospitalisé·e·s pour COVID-19 - Motivations et enjeux.

The SARS-CoV-2 pandemic is putting our healthcare system under exceptional pressure, given the number of affected patients. In a context of limited human healthcare resources, senior medical students represent a valuable workforce that can quickly be mobilized for patient care. This is the approach followed in Switzerland and other countries, in several outpatient structures or inpatient services, including the Department of Internal Medicine, of the Lausanne University Hospital (CHUV). In this article, we first give the floor to students who responded to our call. We conclude with important considerations in terms of students' clinical supervision. It is reminded that the involvement of students in the care of COVID-19 patients should only occur on a vo luntary basis.

La pandémie de COVID-19 met notre système de santé sous une pression exceptionnelle, au vu du nombre de patient·e·s atteint·e·s. Dans un contexte de ressources humaines médico-soignantes limitées, les étudiant·e·s en médecine avancé·e·s dans leur cursus représentent un renfort très précieux, rapidement mobilisable auprès des patient·e·s. C'est la démarche suivie en Suisse et ailleurs dans le monde par diverses structures ambulatoires ou services hospitaliers, dont le Service de médecine interne du Centre hospitalier universitaire vaudois (CHUV). Dans cet article, nous donnons tout d'abord la parole aux étudiant·e·s qui ont répondu à notre appel. Nous terminons par des considérations importantes quant à l'accueil et l'accompagnement de ces étudiant·e·s. Il est rappelé que l'engagement d'étudiant·e·s auprès de patient·e·s souffrant de COVID-19 devrait se faire sur une base volontaire uniquement.

[Organizational Impacts and Clinical Challenges of the COVID-19 Pandemic on a Swiss Tertiary Internal Medicine Department]. / Impacts organisationnels et défis cliniques de la pandémie COVID-19 pour un service hospitalier de médecine interne universitaire.

The rapid progression of COVID-19 is an organizational challenge for all hospitals. To secure the patient overflow, the Department internal medicine of the University Hospital of Lausanne increased nurse and medical workforces as well as bed capacity by 65 %, with extraordinary help from other departments. The implemented crisis management stood upon three pillars : a crisis management team, steering documents and internal communication. In this new form, the Department had already taken care of 442 COVID-19 admissions by April 16, 2020. Alongside organizational challenges, clinical issues such as rapid respiratory distress, clinical suspicions with negative PCR and treatment uncertainties in the absence of sufficient evidence were overcome. Despite the peak of the pandemic appearing to have passed, the next phase could be just as complicated.

La progression rapide du COVID-19 constitue un défi organisationnel pour tous les hôpitaux. Pour anticiper un afflux important de patients, le service de médecine interne du CHUV a ainsi augmenté ses forces de travail médico-soignantes et son nombre de lits de 65 % avec un soutien extraordinaire de toute l'institution. Pour opérer ces changements majeurs, l'organisation de crise mise en place s'est appuyée sur trois piliers : une cellule de conduite, des documents de pilotage et une communication interne. Sous cette nouvelle forme, le service a pris en charge 442 hospitalisations COVID-19 jusqu'au 16 avril 2020. Si les enjeux organisationnels ont été majeurs, la gestion des situations complexes, comme les manifestations respiratoires et les multiples incertitudes cliniques diagnostiques et thérapeutiques, ont été également une gageure. Le pic de la pandémie semble passé, mais la prochaine phase pourrait constituer un nouveau défi organisationnel.

[Cutaneous manifestations of nutritional deficiencies]. / Manifestations cutanées de carences nutritionnelles, ou quand l'examen de la peau alimente le diagnostic.

In elderly or chronically ill patients, nutritional deficiencies are common and the presence of related skin lesions is not unusual. Recognition of such cutaneous involvement is important regarding the diagnosis essentially based on clinical elements. By using some clinical case reports, we will describe several pathologies related to nutritional deficiencies like scurvy, pellagra and acquired acrodermatitis enteropathica.

Dans nos populations de patients vieillissants ou atteints de maladies chroniques, les carences nutritionnelles sont fréquentes et la présence de manifestations dermatologiques associées n'est pas rare. La reconnaissance de telles atteintes cutanées est importante pour le diagnostic qui est essentiellement clinique. A l'aide de vignettes cliniques, nous allons discuter ici de pathologies carentielles comme le scorbut, la pellagre ainsi que l'acrodermatite entéropathique acquise.

[Medicine and gender : which challenges for clinical practice ?] / Médecine et genre : quels enjeux pour la pratique ?

Biological sex and social gender jointly influence health. Failure to take into account differences in health between women and men is an issue. What is more, undue differences based on stereotypes can also lead to biased care. This article illustrates the influence of sex and gender on health through clinical situations affecting various dimensions of medical care (diagnosis, investigations, treatments, prognosis). It also gives tools and introduces a project aimed at integrating the gender dimension into the pregraduate education of medical students at the University of Lausanne. The aim is to ensure equitable quality care between women and men, taking into account gender specificities based on unbiased scientific evidence.

Le sexe biologique et le genre social influencent conjointement la santé. La non-prise en compte des différences en santé entre les hommes et les femmes est problématique. En outre, des différences non justifiées sur la base de préconceptions stéréotypées peuvent également conduire à une prise en charge biaisée. Cet article illustre l'influence du sexe et du genre en santé au travers de quelques situations cliniques touchant différents aspects de la prise en charge médicale (diagnostic, investigations, traitements, pronostic). Il donne aussi des outils et présente un projet visant à intégrer la dimension du genre dans le cursus prégradué des étudiant-e-s de médecine de l'Université de Lausanne. L'objectif est d'assurer une prise en charge équitable et de qualité des femmes et des hommes tenant compte des spécificités de genre et basée sur des preuves scientifiques non biaisées.

IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.

BACKGROUND: Data on patients affected by chronic mucocutaneous candidiasis underscore the preponderant role of IL-17 receptor A (IL-17RA) in preserving mucocutaneous immunity. Little is known about the role of adenosine deaminase (ADA) 2 in regulation of immune responses, although recent reports linked ADA2 deficiency with inflammation and vasculitis. OBJECTIVE: We sought to investigate the mechanisms of chronic inflammation and vasculitis in a child lacking IL-17RA and ADA2 to identify therapeutic targets. METHODS: We report a family with 2 siblings who have had recurrent mucocutaneous infections with Candida albicans and Staphylococcus aureus and chronic inflammatory disease and vasculitis since early childhood, which were refractory to classical treatments. Array-based comparative genomic hybridization analysis showed that both siblings are homozygous for a 770-kb deletion on chr22q11.1 encompassing both IL17RA and cat eye critical region 1 (CECR1). Immunologic studies were carried out by means of flow cytometry, ELISA, and RIA. RESULTS: As expected, in the affected child we found a lack of IL-17RA expression, which implies a severe malfunction in the IL-17 signaling pathway, conferring susceptibility to recurrent mucocutaneous infections. Surprisingly, we detected an in vitro and in vivo upregulation of proinflammatory cytokines, notably IL-1ß and TNF-α, which is consistent with the persistent systemic inflammation. CONCLUSIONS: This work emphasizes the utility of whole-genome analyses combined with immunologic investigation in patients with unresolved immunodeficiency. This approach is likely to provide an insight into immunologic pathways and mechanisms of disease. It also provides molecular evidence for more targeted therapies. In addition, our report further corroborates a potential role of ADA2 in modulating immunity and inflammation.