Immunogenicity of a 3rd Dose of Mrna Covid-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond to 2 Prior Doses

Purpose: Kidney transplant recipients (KTRs) have diminished immune response and protection after 2-dose mRNA COVID-19 vaccination. It is unknown if additional doses improve neutralization of variants of concern (VOC) in KTRs with prior poor seroresponse. Method(s): Adult KTRs with negative (<0.8 U/mL) or low (<=50 U/ml) anti-RBD Ig (Roche Elecsys anti-SARS-CoV-2-S) after 2-dose mRNA series were given a homologous 3rd dose (D3). Anti-RBD and VOC surrogate neutralization (%ACE2i) were measured 30 days post D3;responses were stratified by baseline anti-RBD. Reactogenicity, serial SARS-CoV-2 swabs, and donor-specific antibody (DSA) were assessed. Result(s): 81 KTRs (50% negative anti-RBD) received D3 (72% BNT162b2, 28% mRNA-1273) at median 167 days post D2 (Table). Median (IQR) anti-RBD increase was 410 (8-2309) U/mL with 69% (40% negative vs 98% low anti-RBD) achieving day 30 anti-RBD >50 U/ml (Fig1a). 22% remained seronegative. Non-response was associated with lower baseline lymphocyte count (median 770 vs 1160 cells/ uL;p=0.05) and IgG (median 779 vs 979 mg/dL;p<0.01), but not demographics, vaccine, or immunosuppressives. Median (IQR) delta variant %ACE2i increased from 6% (3-7) to 10% (4-22) (p<0.001), a 1% (0-5) increase in negative vs 13% (5-25) in low anti-RBD. %ACE2i was linearly associated with anti-RBD >=100 U/ mL (all VOC shown in Fig1b);64% of KTRs with anti-RBD >=250 U/mL had delta %ACE2i >20. There were 3 cases of mild-moderate COVID-19 >=7 days post-D3, with pre-infection anti-RBD <0.4, 22, 76 U/mL and delta %ACE2i 6, 9, and 16, respectively. There was no acute rejection, nor increased or de novo DSA. Conclusion(s): A 3rd mRNA vaccine dose increased anti-RBD and VOC neutralization in KTRs without inducing clinical alloimmunity, yet 45% with negative baseline anti-RBD remained seronegative without delta variant neutralization. Trials are ongoing to test immune response augmentation in this subgroup via temporary immunosuppression reduction or heterologous boosting.

Higher Proinflammatory Cytokines Are Associated with Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

Purpose: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if pre-vaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. Method(s): A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, with comparison to 16 healthy controls (HCs). Anti-spike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detectionbased multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n=20 analytes). Concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine, were compared using Wilcoxon-rank-sum test with false discovery rates (FDR) computed to correct for multiple comparisons. Result(s): In the study population, 100% of HCs, 59% of SOTRs after two doses and 63% of SOTRs after three doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in cytokine levels between SOTRs with high vs low-titer antibodies after two doses of vaccine. However, as compared to poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher pre-third dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1alpha, and TNF-alpha (FDR <0.05). Conclusion(s): A specific inflammatory profile or immune state may identify which SOTRs are likely to develop stronger sero-response and possible protection after a third dose of SARS-CoV-2 vaccine.

Contributions et défis des pharmaciens d'officine pendant la pandémie de COVID-19 en France

Introduction Les soins de santé en France ont été profondément touchés par la pandémie de COVID-19, mobilisant de façon inédite les professionnels de santé. Dans le secteur des soins primaires, les pharmaciens d'officine ont joué un rôle important dans la réponse de première ligne à la COVID-19. Cette étude visait à explorer les expériences et les perceptions des pharmaciens d'officine concernant l'exercice officinal et l'implémentation de nouveaux services de santé publique en officine pendant la pandémie de COVID-19. Matériels et méthodes Des entretiens qualitatifs individuels semi-structurés ont été conduits entre février et mai 2021 avec des pharmaciens d'officine exerçant en France. Les participants ont été recrutés par le biais d'une URPS pharmaciens et par échantillonnage boule de neige. Les entretiens ont été enregistrés, retranscrits verbatim puis analysés de façon thématique. Résultats Seize pharmaciens d'officine ont participé aux entretiens. Les pharmaciens interrogés ont rapporté avoir exercé un large éventail d'activités en lien avec la crise sanitaire en plus de la poursuite des services officinaux habituels. Les participants ont décrit avoir souvent été le premier recours des usagers pour des informations fiables et officielles sur la COVID-19. Les répondants ont par ailleurs raconté avoir joué un rôle de prévention contre la propagation du SARS-CoV-2 par l'éducation sur les mesures d'hygiène et de distanciation sociale, l'adaptation des locaux des officines ainsi que le contact tracing. Certains participants ont également évoqué avoir joué un rôle dans la gestion de l'anxiété et la lutte contre la désinformation du grand public. Les répondants ont aussi déclaré avoir participé à la prise en charge diagnostique de la COVID-19 en procédant initialement au triage et à l'orientation vers les centres de dépistage puis en proposant à partir d'octobre 2020 des tests de dépistage en officine. Les participants ont également rapporté avoir été impliqués dans la campagne de vaccination contre la COVID-19, tout d'abord en éduquant le public sur les vaccins contre la COVID-19, en facilitant leur distribution vers les cabinets de médecine générale puis en administrant des doses vaccinales à l'officine à partir de mars 2021. Par ailleurs, des participants ont expliqué avoir rencontré plusieurs difficultés dans leur exercice pendant la pandémie telles que des directives officielles multiples et changeantes (n=9/16, 56 %), l'angoisse et la désinformation des usagers en lien avec la COVID-19 (n=9/16, 56 %), le manque d'observance de l'isolement par certains usagers (n=5/16, 31 %) et la méfiance vis-à-vis des vaccins (n=6/16, 38 %). Conclusion Cette étude suggère que les pharmaciens d'officine ont joué un rôle essentiel dans la réponse sanitaire face à la pandémie de COVID-19, en assurant la continuité des services pharmaceutiques et en adoptant progressivement de nouvelles activités d'éducation, de diagnostic et de vaccination. Les missions des pharmaciens d'officine lors de la pandémie de COVID-19 suggèrent qu'ils pourraient être davantage considérés comme des partenaires dans l'organisation de la réponse sanitaire aux maladies infectieuses émergentes. Aucun lien d'intérêt

Comparison of outcomes in sot recipients during two eras of covid-19 therapeutics

Purpose: COVID-19 therapies have evolved over time, but little is known regarding outcomes in SOT recipients treated with newer therapeutic agents such as remdesivir, dexamethasone, and convalescent plasma. We sought to compare outcomes including mortality, rejection, and renal function in a retrospective cohort of SOT recipients with COVID-19 treated during two different eras of therapy. Methods: 40 SOT recipients hospitalized for COVID-19 at our center comprised Era 1 (Mar-May 2020, 20 patients) and Era 2 (Jun-Aug 2020, 20 patients). Data were collected on demographics, comorbidities, renal function, and mortality at time points out to 90 days after COVID-19 infection. Results: Patients in Era 1 received hydroxychloroquine (11/20, 55%), tocilizumab (5/20, 25%) and/or convalescent plasma (3/20, 15%) as targeted therapy;patients in Era 2 received primarily remdesivir (8/20, 40%), dexamethasone (6/20, 30%), and/or convalescent plasma (13/20, 65%). Mortality was 1/20 in Era 1 and 0/20 in Era 2. MMF was held in 33/35 (94%) of patients. Acute kidney injury was present on presentation in 14/40 (35%). The median (IQR) decrease in SCr (mg/dl) between admission and last followup was 0.5 (0.4-0.6) and 0.1 (0-0.4) in patients who had and had not received remdesivir, respectively (p=0.02), 0.5 (0.1-0.6) and 0.1 (0-0.3) in patients who had and had not received plasma, respectively (p=0.09). Antibodymediated rejection (AMR) occurred in 2 patients in Era 1 and 0 patients in Era 2. Acute cellular rejection (ACR) occurred in 1 patient in Era 1 and 0 patients in Era 2. Conclusions: SOT recipients treated in Era 2, when the major targeted therapies were remdesivir, dexamethasone, and convalescent plasma, were not at higher risk for renal dysfunction, ACR, or AMR in the aftermath of COVID-19;rejection was uncommon in both eras and mortality was low in both eras. While awaiting detailed safety studies, these results suggest against renal toxicity or triggering of alloimunity in those receiving newer therapies.

Solid organ transplant recipient attitudes towards a SARS-CoV-2 vaccine

Purpose: An effective and widely-accepted SARS-CoV-2 vaccine could protect the community and vulnerable populations. We investigated the attitudes of solid organ transplant recipients (SOTRs) towards a SARS-CoV-2 vaccine and identified potential barriers to vaccination. Methods: We conducted a national survey of SOTRs between November 11 - December 2, 2020 through the network and social media platforms of the National Kidney Foundation. We studied 3 major domains: a) attitudes towards a vaccine, b) impact of the pandemic on daily life, and c) impact on mental health. Results: Among 1308 SOTRs, 783 (59.9%) were female and 1035 (79.1%) were White. Respondents were evenly distributed throughout the US and were largely college graduates (829, 63.4%) and married (830, 63.5%). Half (647, 49.5%) of SOTRs would be either unsure or unwilling to receive a SARS-CoV-2 vaccine once available (Table 1). Major concerns included side effects (537, 85.2%), lack of rigor in vaccine development (439, 69.7%), and incompatibility with organ transplant (482, 75.4%). However, 1135 (86.8%) SOTRs would be willing to receive a vaccine if recommended by a transplant provider. A small fraction (161 12.3%) were in self-isolation and severe anxiety related to the COVID-19 pandemic remained low (25, 1.9%). There were no significant differences in vaccine attitudes after the announcement of 94.5% efficacy in the mRNA-1273 vaccine (Moderna, Inc.). Conclusions: Transplant recipients expressed large amounts of skepticism in a potential SARS-CoV-2 vaccine, even after announcements of high vaccine efficacy. However, transplant providers may be the defining influence in vaccine acceptance due to the trust vested in them.

Streamlining the pathway to urgent outpatient cholecystectomy – A quality improvement project

Purpose: It is increasingly recognised that patient outcomes and satisfaction with ‘hot’ cholecystectomy are better than those for delayed surgery for cholecystitis. At Belfast Health and Social Care Trust it has not been possible to manage all eligible patients surgically on their index admission within the allotted resources. In addition, the route to outpatient cholecystectomy was ineffective introducing multiple delays for patients. This project aimed to identify the sources of delay and streamline the pathway. Methods: Using quality improvement methodology 927 consecutive admissions with acute biliary pathology were followed over 16 months and analysed fully mapping the existing pathways, identifying key interfaces and delays on the patients’ journey to surgery. Results: Several barriers were identified including unnecessary clinic visits, redundant pre-assessment of fit patients and missed opportunities to provide procedure information or obtain consent. Collaboration with the anaesthetic team led to development of a pre-assessment screening questionnaire which was included in a resource pack introduced for biliary admissions. This also contained a decision-making tool / pathway flowchart, information leaflets, consent and haemovigilence forms. This increases the potential to maximise decision-making and preparations during the index admission. Unfortunately, due to the impact of COVID-19 on elective operating, few patients (n=35) have completed the journey through the new pathway, but ongoing data collection and analysis is anticipated to show significant benefits. Conclusion: Employing the principles of improvement science has led to a remodelled pathway to urgent cholecystectomy which is hoped to increase efficiency and patient satisfaction.

Séroprévalence des anticorps anti-SARS-CoV-2 après la première vague épidémique au sein d’une population vulnérable

Introduction La pandémie de Covid-19 est apparue comme un révélateur des inégalités sociales de santé. En mars 2020, de nombreux cas ont été déclarés dans trois quartiers défavorisés où vit une importante communauté gitane. Une étude de séroprévalence a été menée en juillet 2020 afin d’évaluer le niveau de contamination dans ces quartiers à l’issue de la première vague et d’identifier des facteurs associés à la séropositivité. Matériels et méthodes Cette étude est une enquête transversale menée auprès de la population de 6 ans et plus de ces trois quartiers. Les logements ont été sélectionnés par tirage systématique et les participants par tirage aléatoire. Cette sélection a été réalisée par des enquêteurs terrain préalablement formés. La passation des questionnaires et les prélèvements sanguins des participants ont été effectués dans des centres Covid dédiés. Ces prélèvements ont été soumis à des tests de détection des anticorps IgG et IgM grâce au test immunologique EIecsys® Anti-SARS-CoV-2. La séroprévalence a été estimée sur les données redressées et des facteurs de risque associés ont été recherchés à partir d’un modèle de régression logistique. Résultats Au total, 700 personnes ont participé à l’étude. La séroprévalence des anticorps anti-SARS-CoV-2 était de 35,4% (IC95 % : 30,2–41,0), avec des variations significatives selon le quartier (13,9 %, 17,1 % et 46,7 %). Parmi les personnes séropositives, 21,7 % (14,1–31,8) n’avaient déclaré aucun symptôme entre le 24 février 2020 et la date d’enquête. Les femmes avaient un risque plus élevé d’être séropositives (odds ratio ajusté (ORa)=1,8 [1,0–3,3], p=0,034), de même que les personnes âgées de 15–64 ans en comparaison avec les personnes de 65 ans et plus (15–19 ans : ORa=9,1 [2,8–29,8], p<0,001 ;20–64 ans : ORa=4,5 [2,0–10,1], p<0,001). La prévalence de l’obésité était de 40,7 % (35,8–45,8) et les personnes obèses étaient plus susceptibles d’être séropositives (ORa=2,0 [1,1–3,8], p=0,024). La présence de cas cliniques de la COVID-19 intrafamiliaux augmentait le risque d’être séropositif (Un cas : ORa=2,5 [1,3–5,0], p=0,007). Dans le quartier le plus touché, le risque d’être séropositif était supérieur pour les personnes vivant dans un logement de petite taille (1 ou 2 pièces vs 4 pièces ;ORa=2,8 [1,2–6,3], p=0,016). Le fait de travailler pendant le confinement était associé à une baisse de la probabilité de séropositivité (ORa=0,18 [0,03–1,0], p=0,048). Conclusion La transmission du SARS-COV-2 a été importante dans cette population vulnérable lors de la première vague épidémique de la COVID-19. Ces résultats soulignent la nécessité de renforcer et d’adapter des mesures de prévention, en prenant en compte l’ensemble des déterminants sociaux de la santé et notamment les conditions de logement.

Team time: An online strategy of storytelling as part of reflective practice to improve staff wellbeing within a paediatric emergency department during the coronavirus pandemic

Aims/Objectives/Background Team Time was developed by the Point of Care Foundation in response to the coronavirus pandemic. It is a 45-minute reflective practice using storytelling. It provides an opportunity for people taking part to share recent experiences of their work in health and social care, focusing on participants' emotional and social response to their work. Unlike Schwartz Rounds, the audience is restricted in numbers (maximum 30), is drawn from a single department of a healthcare site rather than from across the organisation, is run and facilitated using virtual platforms, and relays stories from the recent (not distant) past. Methods/Design Two facilitators already trained in delivering Schwartz Rounds (one PEM consultant from the department plus one Trust clinical psychologist) were given additional specific training for running Team Time in March 2020. Six sessions between April and July 2020 were held. The formats of these sessions were as per guidance set by the Point of Care Foundation (UK). A theme for each session was set in advance, with two storytellers invited and prepared in advance by the two facilitators. Two storytellers related a five minute story each uninterrupted, followed by a facilitated discussion with the audience to share their own experiences and/or resonances to the stories told. Standardised web surveys designed by the Point of Care Foundation designed to collate both quantitative an qualitative feedback were distributed by E-mail to all participants the same day. Results/Conclusions Survey respondents n=40 85% strongly agreed that Team Time would help them work better with colleagues. 90% plan to attend Team Time again. 95% would recommend Team Time to colleagues. 92.5% felt that the sessions overall were either excellent or exceptional. Qualitative feedback themes included: not feeling alone;the benefits of hearing perspectives of different roles;and the advantages of sharing honest feelings in a boundaried, reflective space.

Surveillance of clustered cases of COVID-19 in occitania: completeness, results of the surveillance over 6 months and perspectives

Introduction - The objective of this article is to evaluate the completeness of data collection of the surveillance system of COVID-19 clusters set up in May 2020 by Sante publique France, and to describe surveillance data. Methods - The study focuses on clusters recorded between May 11 and October 28, 2020 in the MONIC application in Occitania (France). The completion rate of the data collection was studied by month of registration of the clusters, by type of community and by level of criticality. Cluster characteristics were described when completeness was sufficient. Results - The total number of clusters was 701, with a peak of 363 in October. The completeness of the data decreased from the month of August, in particular for the variables "size of the exposed population", "death" and "hospitalization", and for the variables used for the evaluation of the criticality and from September for those allowing evaluate the status. The clusters in medical-social establishments and services were the most common, followed by clusters in school, university and professional settings. Conclusion - The surveillance system made it possible to characterize the COVID-19 clusters with certain limitations due to the quality of the data collection. In the future, it would be interesting to secure the collection of the variables essential for the evaluation of criticality, to lighten the system in times of high viral circulation and to characterize the circumstances of contamination.

COVID-19 in the vulnerable population of the Saint-Jacques and Haut-Vernet districts of Perpignan (France): health surveillance carried out using local data

A sudden increase in the number of cases and deaths with a diagnosis of COVID-19 was observed in Perpignan strating on 13 March 2020. This increase particularly concerned the population of the Saint-Jacques and Haut-Vernet districts, which mainly belongs to the gypsy community. The signal encouraged the implementation of a specific surveillance of this this epidemic, relying mainly on data from dedicated COVID centers. The indicators monitored have shown a rapid growth in the number of cases in the last two weeks of March and then decline until the end of containment (early May). The circulation of the virus had been greater in the two targeted districts in Perpignan, where more than 2% of the population reported clinical symptoms compatible with a COVID-19 infection during their consultation. From 24 February to 10 May 2020, the relative incidence of consultations for suspected COVID-19 in Saint-Jacques and Haut-Vernet districts were three times higher than in the rest of the city of Perpignan, reflecting a significant burden disease. These surveillance results call for additional studies to better quantify the health impact of this type of event and identify the key factors on which it would be possible to act to limit the circulation of the virus in these communities.

Organisation of a general hospital in a COVID-19 disaster situation

In order to deal with an unprecedented health crisis, how did a general hospital centre turn into a COVID hospital and had to double its capacity in intensive care beds, while continuing its public service missions? The transformation of a post-interventional monitoring room into a COVID intensive care unit was one of the elements in responding to this health challenge. Feedback from the Chartres hospital centre (28). © 2020 z Afin de faire face à une crise sanitaire inédite, comment un centre hospitalier général s'est-il transformé en hôpital Covid et a doublé sa capacité en lits de réanimation, tout en continuant ses missions de service public ? z La transformation d'une salle de surveillance postinterventionnelle en réanimation Covid a été un des éléments pour répondre à cet enjeu sanitaire z Retour d'expérience du centre hospitalier de Chartres (Eure-et-Loir). © 2020