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1.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326281

ABSTRACT

Background: The omicron variant has spread globally at unprecedented speed due to a combination of epidemiological and virological factors that still need to be fully unraveled. Although boosting of immunity in vaccinated populations has proven to increase the antibody recognition for this variant, we still ignore the impact that this intervention has on protection from infection and disease. Methods: Relying on a live virus neutralization assay and a commercial chemiluminescence immunoassay targeting antibodies against the receptor binding domain (RBD) of the parental Spike protein, we tested the efficacy of homologous and heterologous booster vaccinations in inducing antibodies against SARS-CoV-2 parental, delta, beta and omicron variants by history of SARS-CoV-2 infection and age of population. Booster vaccination was performed with the BNT126b2 vaccine, while individuals who underwent heterologous booster vaccination were primed with the ChAdOx1 nCov-19 vaccine. Moreover, we studied the impact that prior immunity has on vaccination, in mildly infected individuals who received 2-3 doses of the BNT1262b vaccine at different times after infection. Children previously infected with delta were evaluated 3·5 months after infection. To translate neutralization data into estimates of protection, we relied on published predictive models and inferred variant-specific thresholds of protection for both assays and assessed the accuracy of the commercial assay at identifying highly protected individuals. Findings: We confirm that boosting significantly restores the ability of antibodies to recognize omicron and other variants, and that the homologous protocol with the BNT126b2 vaccine achieves higher and more broadly reactive neutralizing antibody titers, than those observed among individuals who crossed-over vaccines. On the other hand, mild prior infection with the parental virus and subsequent homologous vaccination with BNT126b2 induces high antibody levels, but with moderate breadth of response, while children aged 5-11 show negligible neutralizing antibodies against the omicron variant few months from infection. Neutralizing and binding antibodies correlate across all variants and allow the identification of variant-specific anti-RBD thresholds for 90% protection efficacy. Interpretation: Boosting with the BNT126b2 vaccine is an immediate and effective measure to increase the protection against omicron, in naïve, as well as in previously infected individuals. Identification through serological commercial assays of thresholds of protection against the omicron and delta variants is a crucial step towards large-scale serosurveys to finely assess infection risk both at population and individual level.

2.
Front Immunol ; 12: 741796, 2021.
Article in English | MEDLINE | ID: covidwho-1477826

ABSTRACT

Background: The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population. Methods: Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1-3.7) and 6.1 (5.3-7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR). Results: Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes. Conclusions: Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections , B-Lymphocytes, Regulatory/immunology , COVID-19/pathology , T-Lymphocytes, Regulatory/immunology , Adult , Child , Child, Preschool , Cytokines/blood , Female , Humans , Lymphocyte Count , Male , Middle Aged , Pathogen-Associated Molecular Pattern Molecules/blood , Prospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Viral Load/immunology
3.
Pediatr Allergy Immunol ; 32(8): 1833-1842, 2021 11.
Article in English | MEDLINE | ID: covidwho-1282025

ABSTRACT

BACKGROUND: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.


Subject(s)
COVID-19 , Antibodies, Viral/blood , B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Child , Humans , Immunoglobulin G/blood , SARS-CoV-2 , Serologic Tests
4.
Pediatrics ; 148(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1280670

ABSTRACT

BACKGROUND: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS: We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4-13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS: Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , SARS-CoV-2/immunology , Adolescent , Adult , Age Factors , COVID-19/immunology , COVID-19 Serological Testing , Child , Child, Preschool , Cluster Analysis , Data Collection , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Italy , Neutralization Tests , Prospective Studies , Symptom Assessment , Time Factors
5.
Cell Rep ; 34(11): 108852, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1135278

ABSTRACT

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Adaptive Immunity/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/virology , Child , Humans , Immunity, Humoral/immunology , Proteome/immunology , SARS-CoV-2/immunology , Signal Transduction/immunology , Viral Load/immunology
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