Prevalence and Determinants of Cellular Immunity Against Sars-Cov-2 in Heart Transplant Recipients: A Cross-Sectional Study

Serology studies provide limited information on immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cross-sectional study aimed to assess prevalence and determinants of anti-SARS-CoV-2 cellular immunity in a cohort of heart transplant (HT) recipients. All consecutive HT recipients followed-up at our outpatient clinic between February and June 2022 providing informed consent were included in this observational cross-sectional study. We quantified SARS-CoV-2 Spike (S)-reactive and Nucleocapsid (N)-reactive T cells using enzyme-linked immunospot assay. A positive response was defined as S or N reactivity >8 spots/2 × 105 lymphocytes. Clinical characteristics, laboratory data, immunosuppressive regimen and vaccination status were compared between patients with and without SARS-CoV-2 S-reactive T cells. Categorical variables were described as number (%) and continuous variables with median [IQR]. Among 201 patients (age 58 [45-65] years, 77% males, time since transplantation 51 months [24-81]), 97 (48%) exhibit S-specific T cells, of which 58 had in addition N-reactive T cells. CD4 and CD8 T lymphocyte count, glomerular filtration rate, immunosuppressive regimen were associated with T cell response (Table). Among patients with detectable SARS-Co-V-2 cellular immunity, numbers of S-reactive T cells were higher in patients who had detectable N-reactive T cells (277 vs 93 /106 T cells) (Figure). Our study provides new information on cellular immunity against SARS-CoV-2 in HT recipients. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

HUMORAL RESPONSE to SARS-CoV-2 mRNA VACCINE in HEART TRANSPLANT RECIPIENTS

Background: Recent studies reported poor to moderate humoral response after two vaccine doses in heart transplant recipients (HTR). Currently, French healthcare authorities recommend 2 and 3 vaccine injections for transplant recipients with and without prior SARS-CoV-2 infection, respectively. This study aimed to evaluate level and durability of humoral immunity with this vaccination strategy. Methods: This single-center cohort study included HTR followed at Paris Bichat hospital between January 2020 and September 2021. Analyses were performed using automated immunoassays (Abbot) to quantify anti-spike IgG (cut-off ≥ 7.1 BAU/mL) and anti-nucleocapsid IgG (cut-off index > 0.49), respectively. Categorical variables were described as number (%) and continuous variables with median (IQR). Results: A total of 181 HTR (75.7% males, age 58 y [47-66]) transplanted between June 1990 and June 2021, with cardiomyopathy (n=95), coronary artery disease (n=61), valvular cardiomyopathy (n=19) or other transplant indications were included. Median time from transplantation to first vaccine dose was 4.2 y [1.8-6.6]. 143 HTR (79%) had no SARS-CoV-2 infection history (HTRn) and 38 (21%) contracted the infection (HTRi) (56% before and 42% after vaccination initiation). After 2 vaccine injections, anti-S IgG seroconversion was observed for only 16% (n=12/76) of HTRn. Overall, anti-S IgG titers were lower in HTRn than in HTRi (0.5 [0.2-2.6] vs 578 [1.4-4449] BAU/mL, respectively, p=0.0001). The 3rd vaccine dose enabled to obtain 42% (n=33/72) of seroconversion among HTRn with median anti-S titers of 3.2 BAU/mL [0.4-35.0]. Only half seroconverters HTRn reached the 260 BAU/mL cut-off chosen by French authorities to define vaccination efficacy. Interestingly, these patients seem to have a sustained humoral response 4 months after the 3rd dose. Conclusion: This study gives new insights on the effect of the 3rd vaccine dose in HTR with low rate of seroconversion and low titers of anti-S IgG but sustained humoral response when seroconversion occurs. Studies on vaccine efficacy against SARS-CoV-2 variants and cell-mediated immune response in this cohort are ongoing.

Focus on Middle East respiratory syndrome coronavirus (MERS-CoV).

Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.

Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives

OBJECTIVES: Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. The high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the clinical performances of SARS-CoV-2 nucleocapsid antigen (N-antigen) ELISA detection in serum or plasma using the COVID-19 Quantigene R (AAZ, France) assay. METHODS: Performances were determined on 63 sera from 63 non-COVID patients and 227 serum samples (165 patients) from the French COVID and CoV-CONTACT cohorts with RT-PCR confirmed SARS-CoV-2 infection, including 142 serum (114 patients) obtained within 14 days after symptoms' onset. RESULTS: Specificity was 98.4% (95% confidence interval [CI], 95.3 to 100). Sensitivity was 79.3% overall (180/227, 95% CI, 74.0 to 84.6) and 93.0% (132/142, 95% CI, 88.7 to 97.2) within 14 days after symptoms onset. 91 included patients had a sera and nasopharyngeal swabs collected in the same 24 hours. Among those with high nasopharyngeal viral loads, i.e. Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among those with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia;the lower respiratory tract was explored for 6 of these 8 patients, showing positive RT-PCR in 5 cases. CONCLUSION: This is the first evaluation of a commercially available serum N-antigen detection assay. It presents a robust specificity and sensitivity within the first 14 days after symptoms onset. This approach provides a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.

Caractéristiques cliniques et paracliniques de 4 patients confirmés à COVID-19

Introduction Fin janvier 2020, 4 des premiers cas de COVID-19 diagnostiqués en France ont été pris en charge dans notre établissement de santé de référence. Nous décrivons ici leur évolution. Matériels et méthodes Les données cliniques, virologiques et radiologiques des patients ont été recueillies. La recherche de COVID-19 a été réalisée sur prélèvement nasopharyngé (NP), sérique, urinaire et fécal par RT-PCR semi-quantitative au diagnostic puis régulièrement au cours du suivi. La guérison, clinico-virologique, était définie par une disparition des symptômes et une négativation des RT-PCR sur 2 prélèvements NP à 48heures d’intervalle. Résultats Parmi les 4 patients confirmés, 3 présentations cliniques différentes ont été identifiées : – un cas de défaillance respiratoire à j10 d’évolution : un homme de 31 ans présentant initialement une toux fébrile. La charge virale (CV) SARS-CoV-2 sur le premier écouvillon NP était modérée (26,5 Cycle Threshold [CT]). La radiographie de thorax montrait un syndrome interstitiel bilatéral. À j10, le patient a présenté une détresse respiratoire aiguë avec nécessité d’oxygénothérapie haut débit et surveillance en réanimation. Le scanner thoracique montrait des plages de verre dépoli bilatérales et des opacités alvéolaires. Un traitement par remdesivir a été introduit, arrêté précocement à j5 en raison d’une cytolyse hépatique et d’une éruption cutanée non grave. L’évolution, clinique et virologique, a été favorable avec négativation de la RT-PCR sur prélèvement NP à partir de j11 ;– deux cas de pneumonies non compliquées : 2 femmes de 30 et 46 ans, diagnostiquées à j2, devant une toux et une fièvre modérée. Les radiographies de thorax étaient normales. Les scanners thoraciques réalisés de manière systématique montraient respectivement une condensation alvéolaire et des plages de verre dépoli. Au diagnostic, les CV sur écouvillon NP étaient élevées, 22 et 18,5 CT respectivement. Pour les 2 patientes, les selles étaient positives à SARS-CoV-2. L’évolution a été rapidement favorable avec disparition des symptômes et négativation des RT-PCR sur prélèvement NP à j9 pour l’une et en cours pour l’autre ;– un cas de SDRA : un homme de 80 ans, sans comorbidité majeure, avec pneumonie bilatérale sévère d’emblée compliquée d’une surinfection précoce à Acinetobacter baumannii et Aspergillus flavus. Au diagnostic, la CV sur écouvillon NP était modérée à 29,5 CT. Le SARS-CoV-2 a également été retrouvé en faible quantité dans le sang (36,9 CT) et dans la plèvre (37,3 CT). Un traitement par remdesivir a été introduit. L’évolution du patient a été défavorable avec décès à j24 en défaillance multiviscérale. Conclusion Trois profils cliniques de gravité variable d’infection COVID-19 ont été identifiés, de la pneumonie paucisymptomatique au SDRA. Au 16/02/20, 2 patients étaient guéris et sortis d’hospitalisation, 1 patiente était devenue asymptomatique et en cours de guérison virologique et 1 patient était décédé des suites de complications. Des investigations complémentaires restent nécessaires pour mieux connaître cette infection émergente.