Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 2.495
Filter
1.
Euro Surveill ; 25(23)2020 06.
Article in English | MEDLINE | ID: covidwho-2313322

ABSTRACT

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.


Subject(s)
Antibodies, Viral/blood , Clinical Laboratory Techniques/methods , Coronaviridae Infections/diagnosis , Coronavirus Infections/diagnosis , Coronavirus/immunology , Pneumonia, Viral/diagnosis , Serologic Tests/standards , Severe Acute Respiratory Syndrome/immunology , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/standards , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Predictive Value of Tests , SARS-CoV-2 , Sensitivity and Specificity , Serologic Tests/methods , Severe Acute Respiratory Syndrome/blood
2.
Animal Model Exp Med ; 5(1): 89-93, 2022 02.
Article in English | MEDLINE | ID: covidwho-2270021

ABSTRACT

BACKGROUND: The Omicron (B.1.1.529) SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein. Since the vaccine-induced neutralizing antibody targets are the spike protein, this may lead to the possibility of vaccine-induced humoral immunity escape. METHODS: We measured the neutralizing activity in vitro for Omicron and compared this with wild type (WH-09) and Delta variants in human and monkey sera from different types of immunity. The monkey sera samples were collected at 1 and 3 months post three-dose inactivated (PiCoVacc) and recombinant protein (ZF2001) vaccination. Human sera were collected from 1 month post three-dose inactivated vaccination. RESULTS: In inactivated vaccine sera, at 1/3 months post three-dose, geometric mean titers (GMTs) of neutralization antibody (NAb) against the Omicron variant were 4.9/5.2-fold lower than those of the wild type. In recombinant protein vaccine sera, GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type. In human sera, at 1 month post three-dose inactivated vaccination, GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type. CONCLUSION: This study demonstrated that despite a reduction in neutralization titers, cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19 , Cross Reactions , SARS-CoV-2 , Animals , Antibodies, Neutralizing/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Haplorhini , Humans , Neutralization Tests , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics
3.
N Engl J Med ; 388(7): 609-620, 2023 02 16.
Article in English | MEDLINE | ID: covidwho-2258655

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3). RESULTS: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively). CONCLUSIONS: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).


Subject(s)
Antibodies, Neutralizing , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Aged , Humans , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Double-Blind Method , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/adverse effects , Respiratory Syncytial Virus Vaccines/therapeutic use , Respiratory Syncytial Virus, Human/immunology , Respiratory Tract Infections/blood , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Vaccine Efficacy , Immunogenicity, Vaccine/immunology , Treatment Outcome
4.
Int J Mol Sci ; 24(5)2023 Mar 01.
Article in English | MEDLINE | ID: covidwho-2256883

ABSTRACT

The coronavirus disease 19 (COVID-19) post pandemic evolution is correlated to the development of new variants. Viral genomic and immune response monitoring are fundamental to the surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since 1 January to 31 July 2022, we monitored the SARS-CoV-2 variants trend in Ragusa area sequencing n.600 samples by next generation sequencing (NGS) technology: n.300 were healthcare workers (HCWs) of ASP Ragusa. The evaluation of anti-Nucleocapside (N), receptor-binding domain (RBD), the two subunit of S protein (S1 and S2) IgG levels in 300 exposed vs. 300 unexposed HCWs to SARS-CoV-2 was performed. Differences in immune response and clinical symptoms related to the different variants were investigated. The SARS-CoV-2 variants trend in Ragusa area and in Sicily region were comparable. BA.1 and BA.2 were the most representative variants, whereas the diffusion of BA.3 and BA.4 affected some places of the region. Although no correlation was found between variants and clinical manifestations, anti-N and anti-S2 levels were positively correlated with an increase in the symptoms number. SARS-CoV-2 infection induced a statistically significant enhancement in antibody titers compared to that produced by SARS-CoV-2 vaccine administration. In post-pandemic period, the evaluation of anti-N IgG could be used as an early marker to identify asymptomatic subjects.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , High-Throughput Nucleotide Sequencing , Immunoglobulin G/blood , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sicily/epidemiology
5.
Viruses ; 14(2)2022 01 25.
Article in English | MEDLINE | ID: covidwho-2285589

ABSTRACT

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. The aim of the study was to estimate the SARS-CoV-2 seroprevalence among HCWs in Cochabamba, Bolivia and to determine the potential risk factors. In January 2021, a cross-sectional SARS-CoV-2 seroprevalence study was conducted in 783 volunteer clinical and non-clinical HCWs in tertiary care facilities. It was based on IgG detection using ELISA, chemiluminiscence, and seroneutralisation tests from dried blood spots. Analysis revealed a high seroprevalence (43.4%) of SARS-CoV-2 IgG antibodies. The combination of anosmia and ageusia (OR: 68.11; 95%-CI 24.83-186.80) was predictive of seropositivity. Belonging to the cleaning staff (OR: 1.94; 95%-CI 1.09-3.45), having more than two children in the same house (OR: 1.74; 95%-CI 1.12-2.71), and having been in contact with a close relative with COVID-19 (OR: 3.53; 95%-CI 2.24-5.58) were identified as risk factors for seropositivity in a multivariate analysis. A total of 47.5% of participants had received medication for COVID-19 treatment or prevention, and only ~50% of symptomatic subjects accessed PCR or antigenic testing. This study confirms a massive SARS-CoV-2 attack rate among HCWs in Cochabamba by the end of January 2021. The main risk factors identified are having a low-skilled job, living with children, and having been in contact with an infected relative in the household.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/immunology , Health Personnel/statistics & numerical data , Adolescent , Adult , Antibodies, Viral/immunology , Bolivia/epidemiology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Prevalence , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Seroepidemiologic Studies , Tertiary Healthcare/statistics & numerical data , Young Adult
6.
Science ; 370(6521): 1227-1230, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-2243268

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Neutralization Tests
7.
Epidemiol Prev ; 44(5-6 Suppl 2): 193-199, 2020.
Article in English | MEDLINE | ID: covidwho-2238909

ABSTRACT

BACKGROUND: facing the SARS-CoV-2 epidemic requires intensive testing on the population to early identify and isolate infected subjects. Although RT-PCR is the most reliable technique to detect ongoing infections, serological tests are frequently proposed as tools in heterogeneous screening strategies. OBJECTIVES: to analyse the performance of a screening strategy proposed by the local government of Tuscany (Central Italy), which first uses qualitative rapid tests for antibody detection, and then RT-PCR tests on the positive subjects. METHODS: a simulation study is conducted to investigate the number of RT-PCR tests required by the screening strategy and the undetected ongoing infections in a pseudo-population of 500,000 subjects, under different prevalence scenarios and assuming a sensitivity of the serological test ranging from 0.50 to 0.80 (specificity 0.98). A compartmental model is used to predict the number of new infections generated by the false negatives two months after the screening, under different values of the infection reproduction number. RESULTS: assuming a sensitivity equal to 0.80 and a prevalence of 0.3%, the screening procedure would require on average 11,167 RT-PCR tests and would produce 300 false negatives, responsible after two months of a number of contagions ranging from 526 to 1,132, under the optimistic scenario of a reproduction number between 0.5 to 1. Resources and false negatives increase with the prevalence. CONCLUSIONS: the analysed screening procedure should be avoided unless the prevalence and the rate of contagion are very low. The cost and effectiveness of the screening strategies should be evaluated in the actual context of the epidemic, accounting for the fact that it may change over time.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Computer Simulation , Mass Screening/methods , Models, Theoretical , Pandemics , SARS-CoV-2/immunology , Basic Reproduction Number , COVID-19/epidemiology , COVID-19/transmission , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing/economics , COVID-19 Serological Testing/methods , Cost-Benefit Analysis , False Negative Reactions , False Positive Reactions , Humans , Italy/epidemiology , Mass Screening/economics , Monte Carlo Method , Point-of-Care Testing/economics , Prevalence , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
8.
N Engl J Med ; 388(7): 621-634, 2023 02 16.
Article in English | MEDLINE | ID: covidwho-2243580

ABSTRACT

BACKGROUND: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. METHODS: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-µg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-µg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 µg of BNT162b2 in the pivotal trial. RESULTS: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-µg dose) and 48 children 2 to 4 years of age (3-µg or 10-µg dose). The 3-µg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). CONCLUSIONS: A three-dose primary series of 3-µg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).


Subject(s)
BNT162 Vaccine , COVID-19 , Adolescent , Child , Child, Preschool , Humans , Infant , Young Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , BNT162 Vaccine/immunology , BNT162 Vaccine/therapeutic use , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Immunoglobulin G/blood , Immunoglobulin G/immunology , Vaccines/adverse effects , Vaccines/therapeutic use , Immunogenicity, Vaccine , Treatment Outcome , Vaccine Efficacy
9.
Mem Inst Oswaldo Cruz ; 117: e220072, 2023.
Article in English | MEDLINE | ID: covidwho-2243449

ABSTRACT

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins. OBJECTIVES: Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19. METHODS: For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays. FINDINGS: Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study. MAIN CONCLUSIONS: Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Immunity, Humoral , Humans , Antibodies, Viral/blood , COVID-19/immunology , Cross-Sectional Studies , Immunoglobulin G/blood , SARS-CoV-2 , Viral Proteins
10.
Sci Rep ; 12(1): 21908, 2022 12 19.
Article in English | MEDLINE | ID: covidwho-2186014

ABSTRACT

The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.


Subject(s)
Antibody Formation , BNT162 Vaccine , COVID-19 , Neoplasms , Humans , Antibodies, Viral/blood , BNT162 Vaccine/immunology , COVID-19/prevention & control , Immunoglobulin G/blood , Lymphocytes , Neoplasms/immunology , SARS-CoV-2
11.
Nature ; 615(7952): 482-489, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2185941

ABSTRACT

The protective efficacy of serum antibodies results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as original antigenic sin (OAS)-a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, in detriment to the induction of de novo responses1-5. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-26,7. Precise measurement of OAS-type suppression is challenging because cellular and temporal origins cannot readily be ascribed to antibodies in circulation; its effect on subsequent antibody responses therefore remains unclear5,8. Here we introduce a molecular fate-mapping approach with which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that serum responses to sequential homologous boosting derive overwhelmingly from primary cohort B cells, while later induction of new antibody responses from naive B cells is strongly suppressed. Such 'primary addiction' decreases sharply as a function of antigenic distance, allowing reimmunization with divergent viral glycoproteins to produce de novo antibody responses targeting epitopes that are absent from the priming variant. Our findings have implications for the understanding of OAS and for the design and testing of vaccines against evolving pathogens.


Subject(s)
Antibody Formation , B-Lymphocytes , Immunization, Secondary , Humans , Antibodies, Viral/biosynthesis , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/immunology , Influenza Vaccines/immunology , SARS-CoV-2/immunology , Vaccination , B-Lymphocytes/immunology , Viral Vaccines/immunology
12.
Viral Immunol ; 35(10): 681-689, 2022 12.
Article in English | MEDLINE | ID: covidwho-2188181

ABSTRACT

The majority of children with coronavirus diseases 2019 (COVID-19) are asymptomatic or develop mild symptoms, and a small number of patients require hospitalization. Multisystem inflammatory syndrome in children (MIS-C) is one of the most severe clinical courses of COVID-19 and is suggested to be a hyperinflammatory condition. This study aimed to compare quantitative antibody levels against SARS-CoV-2 spike protein in children with COVID-19 and MIS-C. Blood samples from 75 patients [n = 36 (48%) with mild/asymptomatic (group 1), n = 22 (29.3%) with moderate-to-severe SARS-CoV-2 infection (group 2) and n = 17 (22.6%) patients with MIS-C (group 3)] were analyzed 3 months after COVID-19. The majority of the children with asymptomatic/mild COVID-19 symptoms (80.6%), moderate/severe disease (90.9%), and MIS-C (82.4%) had detectable IgG antibodies to SARS-CoV-2 spike protein (p = 0.567). The mean antibody value against SARS-CoV-2 spike protein was 321.9 ± 411.6 in group 1, 274 ± 261 in group 2, and 220 ± 299 in group 3, respectively (p > 0.05). Patients diagnosed with COVID-19 (asymptomatic/mild+moderate/severe) and those with MIS-C were also compared; the antibody positivity rates [COVID-19 group: 85.5%, MIS-C group: 82.4%, (p = 0.833)] and mean antibody values [COVID-19 group: 303.9 ± 360.3, MIS-C group: 220 ± 299, (p > 0.05)] were similar in both groups. In conclusion, the majority of children with COVID-19 and MIS-C developed a detectable antibody level against SARS-CoV-2 spike protein 3 months after COVID-19. Quantitative antibody levels were similar in both asymptomatic/mild disease, moderate/severe disease, and MIS-C group. Long-term studies evaluating antibody responses in children with COVID-19 and MIS-C are needed for more accurate vaccine schedules.


Subject(s)
Antibodies, Viral , COVID-19 , Spike Glycoprotein, Coronavirus , Child , Humans , COVID-19/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/blood
13.
Immunohorizons ; 7(1): 97-105, 2023 01 01.
Article in English | MEDLINE | ID: covidwho-2201355

ABSTRACT

Although the effectiveness of vaccination at preventing hospitalization and severe coronavirus disease (COVID-19) has been reported in numerous studies, the detailed mechanism of innate immunity occurring in host cells by breakthrough infection is unclear. One hundred forty-six patients were included in this study. To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti-SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Anti-S Abs were classified into two groups according to titer: high titer (≥250 U/ml) and low titer (<250 U/ml). A negative correlation was observed between anti-SARS-CoV-2 S Abs and IFN-λ3 levels (r = -0.437, p < 0.001). A low titer of anti-SARS-CoV-2 S Abs showed a significant association with oxygen demand in patients, excluding aspiration pneumonia. Finally, in a multivariate analysis, a low titer of anti-SARS-CoV-2 S Abs was an independent risk factor for oxygen demand, even after adjusting for age, sex, body mass index, aspiration pneumonia, and IFN-λ3 levels. In summary, measuring anti-SARS-CoV-2 S Abs and IFN-λ3 may have clinical significance for patients with COVID-19. To predict the oxygen demand of patients with COVID-19 after hospitalization, it is important to evaluate the computed tomography findings to determine whether the pneumonia is the result of COVID-19 or aspiration pneumonia.


Subject(s)
Antibodies, Viral , COVID-19 , Interferons , Oxygen , Humans , COVID-19/immunology , COVID-19/therapy , Oxygen/administration & dosage , Pneumonia, Aspiration , SARS-CoV-2 , Antibodies, Viral/blood , Interferons/immunology
14.
Anal Bioanal Chem ; 413(22): 5619-5632, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-2174032

ABSTRACT

In the face of the COVID-19 pandemic, the need for rapid serological tests that allow multiplexing emerged, as antibody seropositivity can instruct about individual immunity after an infection with SARS-CoV-2 or after vaccination. As many commercial antibody tests are either time-consuming or tend to produce false negative or false positive results when only one antigen is considered, we developed an automated, flow-based chemiluminescence microarray immunoassay (CL-MIA) that allows for the detection of IgG antibodies to SARS-CoV-2 receptor-binding domain (RBD), spike protein (S1 fragment), and nucleocapsid protein (N) in human serum and plasma in less than 8 min. The CoVRapid CL-MIA was tested with a set of 65 SARS-CoV-2 serology positive or negative samples, resulting in 100% diagnostic specificity and 100% diagnostic sensitivity, thus even outcompeting commercial tests run on the same sample set. Additionally, the prospect of future quantitative assessments (i.e., quantifying the level of antibodies) was demonstrated. Due to the fully automated process, the test can easily be operated in hospitals, medical practices, or vaccination centers, offering a valuable tool for COVID-19 serosurveillance. Graphical abstract.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Immunoassay/methods , Immunoglobulin G/blood , SARS-CoV-2/immunology , Antigens, Viral/chemistry , Antigens, Viral/immunology , Automation, Laboratory , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/immunology , Immune Sera , Immunoassay/instrumentation , Lab-On-A-Chip Devices , Luminescent Measurements , Phosphoproteins/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Time Factors
15.
Vaccine ; 41(4): 914-921, 2023 Jan 23.
Article in English | MEDLINE | ID: covidwho-2165923

ABSTRACT

With the emergence of the severe acute respiratory syndrome 2 (SARS-CoV-2) B.1.1.529/BA.1 (Omicron) variant in early 2022, Israel began vaccinating individuals 6o years of age or older with a fourth BNT162b2 vaccine. While the decision was based on little experimental data, longer follow-up showed clinical effectiveness of the fourth dose with reduction in the number of severely affected individuals. However, the immune response to fourth vaccine dose in this age group was not yet characterized, and little is known about the immunogenicity of repeated vaccine dosing in this age group. We therefore aimed to evaluate the humoral and cellular immune response pre- and 3-week post- the fourth vaccine dose in patients age 60 years or older. For this purpose, blood samples were collected from donors age 60 years or older, all received their 3rd vaccine dose 5 months prior. Serum samples were evaluated for the presence of anti-Spike protein (anti-S) antibodies (N = 133), and peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry for their ability to respond to the SARS-CoV-2 wild type Spike-glycoprotein peptide mix, Membrane-glycoprotein (M) peptide mix and to the mutated Spike-regions of the Omicron variant (N = 34). Three weeks after the fourth vaccine dose, 24 out of 34 donors (70.5%) showed significant increase in the number of cells responding to the wild type S-peptide mix. Of note, out of 34 donors, 11 donors (32.3%) had pre-boost anti-M T-cell response, none of which had history of confirmed COVID-19, suggesting possible asymptomatic exposure. Interestingly, in M non-responding individuals, no statistically significant increase in the cellular response was observed following stimulation with omicron S-mutated regions. While there are limited data regarding the longevity of the observed response, our results are in accordance with the described clinical efficacy, provide mechanistic evidence to support it and argue against vaccine-induced or age-related immunosenescence.


Subject(s)
BNT162 Vaccine , COVID-19 , Immunogenicity, Vaccine , Aged , Humans , Middle Aged , Antibodies, Viral/blood , BNT162 Vaccine/immunology , COVID-19/prevention & control , Immunity, Humoral , Leukocytes, Mononuclear , Membrane Glycoproteins , SARS-CoV-2 , Immunity, Cellular
16.
Sci Immunol ; 5(54)2020 12 23.
Article in English | MEDLINE | ID: covidwho-2161788

ABSTRACT

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.


Subject(s)
Antibodies, Neutralizing/immunology , Asymptomatic Infections , COVID-19/immunology , T-Lymphocytes/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Cross-Sectional Studies , Humans , SARS-CoV-2/immunology
17.
Front Immunol ; 13: 1050211, 2022.
Article in English | MEDLINE | ID: covidwho-2163024

ABSTRACT

We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm3 were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm3 were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunity, Cellular , Immunity, Humoral , Kidney Transplantation , Humans , Middle Aged , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Cytokines , SARS-CoV-2 , Vaccination , Immunization, Secondary
18.
Lab Med ; 52(5): e137-e146, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-2135433

ABSTRACT

OBJECTIVE: To describe a cross-institutional approach to verify the Abbott ARCHITECT SARS-CoV-2 antibody assay and to document the kinetics of the serological response. METHODS: We conducted analytical performance evaluation studies using the Abbott ARCHITECT SARS-CoV-2 antibody assay on 5 Abbott ARCHITECT i2000 automated analyzers at 2 academic medical centers. RESULTS: Within-run and between-run coefficients of variance (CVs) for the antibody assay did not exceed 5.6% and 8.6%, respectively, for each institution. Quantitative and qualitative results agreed for lithium heparin plasma, EDTA-plasma and serum specimen types. Results for all SARS-CoV-2 IgG-positive and -negative specimens were concordant among analyzers except for 1 specimen at 1 institution. Qualitative and quantitative agreement was observed for specimens exchanged between institutions. All patients had detectable antibodies by day 10 from symptom onset and maintained seropositivity throughout specimen procurement. CONCLUSIONS: The analytical performance characteristics of the Abbott ARCHITECT SARS-CoV-2 antibody assay within and between 2 academic medical center clinical laboratories were acceptable for widespread clinical-laboratory use.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/standards , COVID-19/diagnosis , Immunoassay/standards , Immunoglobulin G/blood , SARS-CoV-2/immunology , Academic Medical Centers , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Humans , Observer Variation , Reproducibility of Results , SARS-CoV-2/pathogenicity , Sensitivity and Specificity , Virginia
19.
BMC Infect Dis ; 22(1): 846, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2115737

ABSTRACT

BACKGROUND: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure. METHODS: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3. RESULTS: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91). CONCLUSION: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants.


Subject(s)
Antibodies, Viral , COVID-19 , Malaria, Falciparum , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Young Adult , Antibodies, Viral/blood , Antigens, Protozoan , COVID-19/epidemiology , Immunoglobulin G , Malaria, Falciparum/epidemiology , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies , Tanzania/epidemiology
20.
Lancet ; 396(10250): 535-544, 2020 08 22.
Article in English | MEDLINE | ID: covidwho-2106188

ABSTRACT

BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/immunology , COVID-19 , Child , Child, Preschool , Female , Humans , Immunoassay , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Point-of-Care Testing , Prevalence , Risk Factors , SARS-CoV-2 , Seroepidemiologic Studies , Spain/epidemiology , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL