ABSTRACT
Introduction: Prevention of COVID by vaccination is important in allogeneic HSCT recipients but impaired humoral and cellular responses have been reported. To gain further insights into the immune defects leading to impaired immune, we performed a high-throughput T cell receptor (TCR) repertoire profiling of cells recovered from allogeneic HSCT recipients or healthy controls after SARS-CoV2 natural infection or mRNA-based vaccination. Method(s): Peripheral blood samples were obtained from allogeneic HSCT recipients after a median of 3 months after COVID- 19 infection (n = 11) or 44 days after vaccination with 3 doses of mRNA-based SARS-CoV-2 vaccines (n = 13). Healthy controls at 1 to 3 months after SARS-CoV-2 infection (n = 10) or vaccination served as controls (n = 10). SARS-CoV-2- specific T cell clonotypes were identified by genomic DNA T-cell receptor (TCR) sequencing (immunoSEQ T-MAPTM COVID, Adaptive). SARS-CoV-2-specific T cell responses were quantified based on IFN-gamma release against a range of peptides from the SARS-CoV-2 proteins using an ELISpot assay. Result(s): HSCT recipients displayed significantly reduced SARS-CoV-2-specific T cell clonotypes compared with HC (p = 0.0037;Figure 1 A-B)as well as a less diverse TCR repertoire as revealed by higher Simpson clonality (p = 0.0079). We also observed significantly lower numbers of IFN-gamma spot forming units after stimulation of PBMCs from HSCT recipients with peptides from both the S protein (p = 0.0068) and the M plus N proteins (p = 0.0067) compared with HC. Performing the same analysis after SARS-CoV-2 mRNA vaccination, we observed a significant reduction in S-protein-specific T cell clonotypes in allogeneic HSCT recipient compared to HC (p = 0.0003;Figure 1D-E). We detected a significantly negative correlation between the Simpson clonality and the number of different S-protein specific T cell clonotypes after vaccination (r2 = 0.55, p = 7.8e-05;Figure 1F). ELISpot analysis of PBMCs recovered after vaccination and stimulated with S-protein peptides revealed significantly lower numbers of IFN-gamma spot forming units in HSCT recipients compared with HC (p = 0.019), confirming the results obtained by TCR-seq. Conclusion(s): Allogeneic HSCT recipients display a quantitative and qualitative defect in cellular SARS-CoV-2-specific responses asscociated with a reduced TCR repertoire after COVID-19 infection and vaccination. (Figure Presented).
ABSTRACT
What’s new in infectious diseases in 2020? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «PIRATE» indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.
ABSTRACT
Allogeneic hematopoietic stem cell transplantation recipients have a higher risk of developing severe forms of COVID-19. Induction of protective immunity through prophylactic vaccination is therefore important. We analyzed humoral responses to two doses of mRNA-based SARS-Cov-2 vaccines in 63 patients transplanted at Geneva University Hospitals, following our institutional priority vaccination program whose inclusion criteria were: minimum 3 months and maximum 3 year since allogeneic HSCT;or at more than 3 years post-transplant with GvHD requiring immunosuppressive drugs;absence of Rituximab in the previous 3 months;absence of steroid treatment with Prednisone ≥ 10 mg/day. Vaccine-induced antibody responses against the SARS-CoV-2 spike protein (anti-S) were assessed in serum using the semi-quantitative El-ecsys® Anti-SARS-CoV-2 immunoassay (Roche).Median age was 54 (18-78) years. The first vaccine dose was administered at a median of 14 (3-150) months after transplantation. Forty-six out of 63 (73%) patients received mRNA-1273 and 17/63 (27%) received BNT162b2 vaccines. Forty-eight out of 63 (76%) allogeneic HSCT recipients showed some degree of humoral response to vaccination based on anti-S IgG. Median levels of anti-S IgG were 815 U/ml. We observed significantly lower anti-S IgG responses in patients receiving the first vaccine dose within 6 months since transplantation (6/13, 46%;median 0.88 U/ml) compared with patients vaccinated after 6 months post-HSCT (42/50, 84%;median 2500 U/ml;p = 0.0016) and lower anti-S IgG responses in patients having received ATG as part of their conditioning (27/41, 66%;median 183 U/ml) compared with patients who did not receive ATG (21/22, 95%;median 2500 U/ml;p = 0.004).
ABSTRACT
Background: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose:We want to determine i) the degree of homology between SARSCoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods: We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, antiapoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARSCoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
ABSTRACT
Aim: Evaluate the kinetics of antibody, plasmablasts (PB) and memory B cells (MBCs) from day 7 up to 8 months following mild COVID-19 Methods: This observational study enrolled 31 RT-PCR confirmed acute mild COVID-19 patients longitudinal followed ups at six visits: 0, +7, +14 +28, +56 and +200 days post onset of symptoms (dpos). Antibodies against S1 domain of the spike and N (nucleocapside) proteins of SARSCoV- 2 were evaluated using ELISA, while neutralization was quantified by a commercially available surrogate (sVNT) assay. Specific PB and MBC were assessed by ELISPOT Results: During mild COVID-19, anti-S1, anti-N as well as neutralizing antibodies were elicited during the first 3 weeks pos, reached a peak between 20-30 dpos and decayed slowly, however 80% of patients had detectable neutralizing antibodies at +200 dpos. S1-specific IgA and IgM PB reached their peak around +14 days while IgG slow increased. All patients developed anti-S1 IgG MBCs by one month that peaked at 49 dpos and remained stable up to 245dpos;anti-N IgG MBCs kinetics was similar but their magnitude was reduced. We next correlated humoral with cellular immune responses and found that anti-S1 IgG and IgA titers at visits +14 and +28 days correlated with plasmablast, while there was a poor correlation between antibody titers and MBCs at visit +56 days that was lost at visit +200 days Conclusion: Mild COVID-19 elicits early and long lasting neutralizing antibodies Antigen-specific PB correlated with early antibody titers, while specific MBCs frequencies were stable and independent of antibody titers up to 245 dpos.
ABSTRACT
Background and Aims: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis. Methods: Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU;n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results: Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64;p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
ABSTRACT
OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2;p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0;p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6;p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4;p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.
ABSTRACT
Considerable efforts have been undertaken to quickly develop COVID-19 vaccines that protect vulnerable adults against severe disease and thus limit the socio-economic and public health impact of the current pandemic. To justify COVID-19 vaccination for the pediatric population, which rarely suffers from severe COVID-19, vaccines will need to have fully demonstrated safety and efficacy in preventing complications and viral transmission. This article summarizes the different vaccine platforms that are currently being tested and discusses practical and ethical aspects of childhood COVID-19 vaccination. It also examines the already deleterious effects of the pandemic on routine childhood vaccine coverage and insists on the imperative to vaccinate all children timely as recommended by national immunization programs.
ABSTRACT
What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project « PIRATE » indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published. Que dire des nouveautés en maladies infectieuses en 2020 ? L’année a été marquée évidemment par la pandémie du Covid-19, motivant une revue dans cet article, des connaissances actuelles sur le SARS-CoV-2 et de sa prise en charge. Les résultats du projet suisse PIRATE ont montré une non-infériorité pour les bactériémies Gram négatif entre une antibiothérapie de 7 jours ou guidée par la CRP face à une durée de 14 jours. Une étude mongolienne n’a pas permis de montrer le bénéfice d’une substitution en vitamine D chez les enfants sur l’incidence de la tuberculose. Le baloxavir, un nouvel antiviral contre la grippe, a été approuvé par Swissmedic. Et enfin, des nouvelles recommandations américaines sur le monitoring thérapeutique de la vancomycine et sur le dépistage universel de l’hépatite C ont été publiées.
ABSTRACT
BACKGROUND: SARS-CoV-2 test kits are in critical shortage in many countries. This limits large-scale population testing and hinders the effort to identify and isolate infected individuals. OBJECTIVE: Herein, we developed and evaluated multi-stage group testing schemes that test samples in groups of various pool sizes in multiple stages. Through this approach, groups of negative samples can be eliminated with a single test, avoiding the need for individual testing and achieving considerable savings of resources. STUDY DESIGN: We designed and parameterized various multi-stage testing schemes and compared their efficiency at different prevalence rates using computer simulations. RESULTS: We found that three-stage testing schemes with pool sizes of maximum 16 samples can test up to three and seven times as many individuals with the same number of test kits for prevalence rates of around 5% and 1%, respectively. We propose an adaptive approach, where the optimal testing scheme is selected based on the expected prevalence rate. CONCLUSION: These group testing schemes could lead to a major reduction in the number of testing kits required and help improve large-scale population testing in general and in the context of the current COVID-19 pandemic.