Objectives
In the post‐SARS‐CoV‐2 pandemic era, “breakthrough infections” are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread ...utilization, the definition of the anti‐Spike (S) immunoglobulin‐G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T‐cell response assessment to enhance the definition of immune memory profile.
Methods
SARS‐CoV‐2 interferon‐gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti‐receptor‐binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated.
Results
Close to 40% of our samples were exclusively IGRA‐positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long‐lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti‐receptor‐binding domain IgG and IGRA levels tended to reduce it.
Conclusion
The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level.
Cell‐mediated immunity and humoral response appeared as essential in the protection against SARS‐CoV‐2 infection. We performed a whole‐blood Interferon‐gamma release assay alongside anti‐RBD‐IgG quantification in a population of immunocompetent healthcare workers followed longitudinally. We report that implementing T‐cell response monitoring offers additional insights to delineate a more comprehensive individual immune profile.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with extensive nonpharmacological interventions, have profoundly altered the epidemiology of major respiratory ...viruses. Some studies have described virus-virus interactions, particularly manifested by viral interference mechanisms at different scales. However, our knowledge of the interactions between SARS-CoV-2 and other respiratory viruses remains incomplete. Here, we studied the interactions between SARS-CoV-2 and several respiratory viruses (influenza, respiratory syncytial virus, human metapneumovirus, and human rhinovirus) in a reconstituted human epithelial airway model, exploring different scenarios affecting the sequence and timing of coinfections. We show that the virus type and sequence of infections are key factors in virus-virus interactions, the primary infection having a determinant role in the immune response to the secondary infection.
Objectives
Impairment of type I interferon (IFN‐I) immunity has been reported in critically ill COVID‐19 patients. This defect can be explained in a subset of patients by the presence of circulating ...autoantibodies (auto‐Abs) against IFN‐I. We set out to improve the detection and the quantification of IFN‐I auto‐Abs in a cohort of critically ill COVID‐19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease.
Methods
The concentration of anti‐IFN‐α2 Abs was determined in the serum of 84 critically ill COVID‐19 patients who were admitted to ICU in Hospices Civils de Lyon, France, using a commercially available kit (Thermo Fisher, Catalog #BMS217).
Results
A total of 21 of 84 (25%) critically ill COVID‐19 patients had circulating anti‐IFN‐α2 Abs above cut‐off (> 34 ng mL−1). Among them, 15 of 21 had Abs with neutralising activity against IFN‐α2, that is 15 of 84 (18%) critically ill patients. In addition, we noticed an impairment of the IFN‐I response in the majority of patients with neutralising anti‐IFN‐α2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralising anti‐IFN‐α2 auto‐Abs. We detected anti‐IFN‐α2 auto‐Abs in COVID‐19 patients' sera throughout their ICU stay. Finally, we also found auto‐Abs against multiple subtypes of IFN‐I including IFN‐ω.
Conclusions
We reported that 18% of critically ill COVID‐19 patients were positive for IFN‐I auto‐Abs, whereas all mild COVID‐19 patients were negative, confirming that the presence of these antibodies is associated with a higher risk of developing a critical COVID‐19 form.
We report here that 18% of severe COVID‐19 patients were positive for autoantibodies able to neutralize type I interferon (IFN). This finding further confirms the deleterious role of IFN‐I auto‐Abs in the antiviral immune response supporting the use of recombinant type I IFNs not targeted by the auto‐Abs (e.g. IFN‐β) in COVID‐19 patients with an impairment of the IFN‐I response.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS‐CoV‐2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. ...Anti‐receptor binding domain (RBD) IgG levels and interferon‐gamma (IFN‐γ) release were evaluated at PCR‐diagnosis of SARS‐CoV‐2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti‐RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti‐RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti‐RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: 0.05−0.64. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti‐RBD IgG titers increased (aOR = 0.08, 95% CI: 0.01−0.41, p = 0.008). IFN‐γ release post‐SARS‐CoV‐2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti‐RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS‐CoV‐2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine
, European health authorities recommended that patients under the age of 55 years who received one dose of ...ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture ...status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median interquartile range of 8 7-9 days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.
Since the onset of the SARS‐CoV‐2 pandemic, the direct causative role of the virus in COVID‐19‐associated chilblains (CAC) has remained under question due to the low rate of positivity to SARS‐CoV‐2 ...nasopharyngeal polymerase chain reaction (PCR) and blood serology.1 Likewise, the suspected pivotal pathogenic role of upregulation of interferon type I (IFN‐I) is mainly indirectly supported by assessment of in situ immune response.2From April 2020 to January 2022, we prospectively assessed children and adults with new‐onset CAC seen in the dermatology, infectious diseases, and adult and paediatric emergency departments, as well as the intensive care unit of the University Hospital of Montpellier. The study was approved by the local institutional review board (ID: 202000442).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Since the SARS-CoV-2 emergence in December 2019, one of the major concerns has been the duration of immune protection after a first episode. This question is of paramount importance for healthcare ...workers (HCWs), who are a highly exposed population and among the first targets of vaccination programmes. To date, the persistence of SARS-CoV-2 antibodies in HCWs 6 months after disease onset (ADO) has not been studied with both a virus neutralisation btest and commercial assays.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Staphylococcus aureus bone and joint infection (BJI) is associated with significant rates of chronicity and relapse. In this study, we investigated how S. aureus is able to adapt to the human ...environment by comparing isolates from single patients with persisting or relapsing BJIs that were recovered during the initial and recurrent BJI episodes. In vitro and in vivo assays and whole‐genome sequencing analyses revealed that the recurrent isolates induced a reduced inflammatory response, formed more biofilms, persisted longer in the intracellular compartments of host bone cells, were less cytotoxic and induced less mortality in a mouse infection model compared with the initial isolates despite the lack of significant changes at the genomic level. These findings suggest that S. aureus BJI chronicization is associated with an in vivo bacterial phenotypical adaptation that leads to decreased virulence and host immune escape, which is linked to increased intraosteoblastic persistence and biofilm formation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background Collecting information on sustainability of immune responses after infection or vaccination is crucial to inform medical decision-making and vaccination strategies. Data on how ...long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity and prevent reinfection with SARS-CoV-2 or its variants is particularly valuable. This study presents a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time. Methods Serum samples from two groups were used in this study: Samples from 20 naturally infected subjects (followed for up to 1 year) and samples from 83 subjects vaccinated with one or two doses of the Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (followed for up to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test developed for the serological confirmation of past-infections, was used to determine the reactivity of six different SARS-CoV-2 antigens. For each subject sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges. This allowed accurate quantification of the corresponding six antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody. Results Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies respectively. Conclusion The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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