Functional study of post-infectious and post-vaccine adaptive immunity against SARS-CoV-2

L’immunité adaptative développée contre le SARS-CoV-2 après infection ou vaccination est le facteur clé dans la protection contre de nouveaux épisodes de COVID-19. Au cours de ce travail, après avoir montré la possibilité d’une réponse cellulaire sans anticorps suite à l’exposition au virus, une étude de cohorte a révélé que les anticorps développés après infection évoluaient différemment en fonction du sexe et persistaient plus d’un an. Un défaut de réponse humorale a été observé chez des patients immunodéprimés traités par rituximab dans les 6 mois précédents ainsi que chez des patients transplantés pulmonaires, en particulier ceux avec une charge virale élevée de TTV reflétant une profonde immunodépression. Enfin, l’étude de 2 cas d’infection post-vaccinale a souligné l’implication possible de différents mécanismes. Ces résultats enrichissent nos connaissances de l’immunité dirigée contre le SARS-CoV-2, cruciales dans la gestion de la pandémie et dans notre projection dans l’avenir.The adaptive immunity developed against SARS-CoV-2 after infection or vaccination is the key factor for the protection against other COVID-19 episodes. In this work, after we showed that an isolated cellular response could be found without antibodies after exposure to the virus, a cohort study revealed that antibodies induced by infection evolve differently according to sex and persist more than one year. A lack of humoral response was observed in patients treated by rituximab over the last 6 months and in lung transplant recipients, particularly in those with a high TTV DNA load reflecting a deep immunosuppression. Finally, the exploration of 2 cases of breakthrough infection in immunocompetent individuals highlighted the possible involvement of distinct mechanisms. These results improve our knowledge of the immunity directed against SARS-CoV-2, which is crucial for the management of the pandemic and for our projection into the future

Étude fonctionnelle de l’immunité adaptative post-infectieuse et post-vaccinale dirigée contre le SARS-CoV-2

The adaptive immunity developed against SARS-CoV-2 after infection or vaccination is the key factor for the protection against other COVID-19 episodes. In this work, after we showed that an isolated cellular response could be found without antibodies after exposure to the virus, a cohort study revealed that antibodies induced by infection evolve differently according to sex and persist more than one year. A lack of humoral response was observed in patients treated by rituximab over the last 6 months and in lung transplant recipients, particularly in those with a high TTV DNA load reflecting a deep immunosuppression. Finally, the exploration of 2 cases of breakthrough infection in immunocompetent individuals highlighted the possible involvement of distinct mechanisms. These results improve our knowledge of the immunity directed against SARS-CoV-2, which is crucial for the management of the pandemic and for our projection into the future.L’immunité adaptative développée contre le SARS-CoV-2 après infection ou vaccination est le facteur clé dans la protection contre de nouveaux épisodes de COVID-19. Au cours de ce travail, après avoir montré la possibilité d’une réponse cellulaire sans anticorps suite à l’exposition au virus, une étude de cohorte a révélé que les anticorps développés après infection évoluaient différemment en fonction du sexe et persistaient plus d’un an. Un défaut de réponse humorale a été observé chez des patients immunodéprimés traités par rituximab dans les 6 mois précédents ainsi que chez des patients transplantés pulmonaires, en particulier ceux avec une charge virale élevée de TTV reflétant une profonde immunodépression. Enfin, l’étude de 2 cas d’infection post-vaccinale a souligné l’implication possible de différents mécanismes. Ces résultats enrichissent nos connaissances de l’immunité dirigée contre le SARS-CoV-2, cruciales dans la gestion de la pandémie et dans notre projection dans l’avenir

Simultaneous primary invasive cutaneous aspergillosis in two preterm twins: case report and review of the literature

Abstract Background Primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. Newborns of very low birth weight present a high risk for this type of infection due to an immaturity of the cutaneous barrier and of the immune system. Case presentation We describe here a case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two male preterm bichorionic biamniotic twins (A & B) were born at a general hospital by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were transferred to our hospital where they receive surfactant, antibiotics and hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical region. The spectrum of antibiotic therapy was broadened and fluconazole was added. The umbilical catheters of the two twins were removed and replaced by epicutaneo-cava venous catheters and the cultures were positive for Aspergillus fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and the incubators were changed. The serum galactomannan was also positive for both twins. At day 10, yellowish lesions appeared in the abdominal region in twin B. He died on day 18 following complications related to his prematurity. Concerning the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B was stopped 1 week later, with a relay by econazole (cream). His condition improved and on day 66 he was transferred for follow-up at the general hospital where he was born. Conclusion The source of contamination by A. fumigatus was not identified, but other similar cases from the literature include construction work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin fragility of preterm newborns is an excellent potential entry point for environmental fungal infections. These cases highlight the importance of suspecting primary cutaneous aspergillosis in extremely low birth weight neonates with rapidly progressive necrotic lesions

Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

International audienceBackground SARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized. Methods We analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally. Results The first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4 + IL-2 + cells) and CD8 effector response (CD8 + IFNγ + cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection. Conclusions An analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies

Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors

International audienceJC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF

Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies

Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA. Additional diagnostic methods õenabling the detection of current or past SARS-CoV-2 infection would be highly beneficial. We assessed 2 immunochromatographic lateral flow assays (LFA-1, LFA-2) and 2 enzyme-linked immunosorbent assay kits (IgA/IgG ELISA-1, IgM/IgG ELISA-2) using 325 samples: serum samples from polymerase chain reaction-confirmed COVID-19 hospitalized patients (n = 55) and healthcare workers (n = 143) and 127 samples from negative controls. Diagnostic performances were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. Clinical sensitivities varied greatly among the assays, showing poor mutual agreement. After 15 dso, ELISA-1 (Euroimmun) and LFA-1 (Biosynex) combining IgM and IgG detection showed the best performances. A thorough selection of serological assays for the detection of ongoing or past infections is advisable

Multilocus sequence typing of clinical Borreliella afzelii strains: population structure and differential ability to disseminate in humans

Abstract Background Lyme borreliosis in humans results in a range of clinical manifestations, thought to be partly due to differences in the pathogenicity of the infecting strain. This study compared European human clinical strains of Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence typing (MLST) to determine their spatial distribution across Europe and to establish whether there are associations between B. afzelii genotypes and specific clinical manifestations of Lyme borreliosis. For this purpose, typing was performed on 63 strains, and data on a further 245 strains were accessed from the literature. Results All 308 strains were categorized into 149 sequence types (STs), 27 of which are described here for the first time. Phylogenetic and goeBURST analyses showed short evolutionary distances between strains. Although the main STs differed among the countries with the largest number of strains of interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical strains were less genetically structured than those previously observed in the European tick population. Two STs were found significantly more frequently in strains associated with clinical manifestations involving erythema migrans, whereas another ST was found significantly more frequently in strains associated with disseminated manifestations, especially neuroborreliosis. Conclusions The MLST profiles showed low genetic differentiation between B. afzelii strains isolated from patients with Lyme borreliosis in Europe. Also, clinical data analysis suggests the existence of lineages with differential dissemination properties in humans

Strong antibody response after a first dose of a SARS-CoV-2 mRNA-based vaccine in kidney transplant recipients with a previous history of COVID-19

No abstract availabl

Sex Differences in the Evolution of Neutralizing Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2

PMCID: PMC7989436International audienceWe measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response