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1.
Cell Rep ; 38(7): 110394, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1719436

ABSTRACT

The emergence of the SARS-CoV-2 Delta variant (B.1.617.2) raises concerns about potential reduced sensitivity of the virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we use a live virus neutralization assay with sera from Pfizer- and Moderna-vaccinated individuals to examine neutralizing antibody titers against SARS-CoV-2 and observe a 3.9- and 2.7-fold reduction, respectively, in neutralizing antibody titers against the Delta variant compared with an early isolate bearing only a D614G substitution in its spike protein. We observe similar reduced sensitivity with sera from hamsters that were previously infected with an early isolate of SARS-CoV-2. Despite this reduction in neutralizing antibody titers against the Delta variant, hamsters previously infected (up to 15 months earlier) with an early isolate are protected from infection with the Delta variant, suggesting that the immune response to the first infection is sufficient to provide protection against subsequent infection with the Delta variant.


Subject(s)
Adaptive Immunity , COVID-19/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/transmission , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Humans , Reinfection/immunology , Reinfection/transmission , Reinfection/virology , SARS-CoV-2/genetics , Viral Load
4.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1661117

ABSTRACT

As SARS-CoV-2 variants accumulate mutations, there is a risk of ineffective neutralizing antibodies against new variants and potential re-infection. Halfmann et al. report that, in the hamster model, previous infection with an early prototypical SARS-CoV-2 isolate prevents re-infection of the Delta variant and its transmission to naïve hamsters.

5.
J Appl Lab Med ; 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1510987

ABSTRACT

BACKGROUND: Diagnostic sensitivities of point-of-care SARS-CoV-2 assays depend on specimen type and population-specific viral loads. Evaluation of these assays require 'direct' specimens from paired-swab studies rather than more accessible residual specimens in viral transport media (VTM). METHODS: Residual VTM and limit-of-detection studies were conducted on Abbott ID NOW™ COVID-19, Quidel Sofia 2™ SARS Antigen FIA, and DiaSorin Simplexa™ COVID-19 Direct assays, with cycle threshold (CT) adjustments to approximate direct-specimen testing based on gene-target doubling each PCR cycle. Logistic regression was used to model assay performance by specimen CT. These models were applied to CT distributions of symptomatic and asymptomatic populations presenting to emergency services to predict the percent of specimens that would be detected by each assay. A 96-sample paired-swab study was conducted to confirm model results. RESULTS: When using direct nasopharyngeal samples and fit with either VTM or limit-of-detection data, percent positivities for ID NOW (symptomatic 94.9%/97.4%; asymptomatic 88.4.0%/89.6%) and Simplexa (symptomatic 97.8%/97.2%; asymptomatic 91.1%/90.8%) were predicted to be similar. Likewise, fit with VTM data, percent positivities for ID NOW with direct nasal specimens (symptomatic 77.8%; asymptomatic 64.5%) and Sofia 2 with direct nasopharyngeal specimens (symptomatic 76.6%, asymptomatic 60.3%) were similar. The paired-swab study comparing direct nasopharyngeal specimens on ID NOW and nasopharyngeal VTM specimens on Simplexa showed 99% concordance. CONCLUSIONS: Assay performance can be modeled as dependent on viral load, fit using laboratory bench study results, and adjusted to account for direct-specimen testing. When using nasopharyngeal specimens, direct testing on Abbott ID NOW and VTM testing on DiaSorin Simplexa have similar performance.

6.
Microbiol Spectr ; 9(2): e0008721, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1381168

ABSTRACT

Uncertainty exists whether mild COVID-19 confers immunity to reinfection. Questions also remain regarding the persistence of antibodies against SARS-CoV-2 after mild infection. We prospectively followed at-risk individuals with and without SARS-CoV-2 for reinfection and monitored the spike and nucleocapsid antibodies. This prospective cohort study was conducted over two visits, 3 to 6 months apart, between May 2020 and February 2021. Adults with and without COVID-19, verified by FDA EUA-approved SARS-CoV-2 RT-PCR assays, were screened for spike and nucleocapsid antibody responses using FDA EUA-approved immunoassays and for pseudoviral neutralization activity. The subjects were monitored for symptoms, exposure to COVID-19, COVID-19 testing, seroconversion, reinfection, and vaccination. A total of 653 subjects enrolled; 129 (20%) had a history of COVID-19 verified by RT-PCR at enrollment. Most had mild disease, with only three requiring hospitalization. No initially seropositive subjects experienced a subsequent COVID-19 infection during the follow-up versus 15 infections among initially seronegative subjects (infection rates of 0.00 versus 2.05 per 10,000 days at risk [P = 0.0485]). In all, 90% of SARS-CoV-2-positive subjects produced spike and nucleocapsid responses, and all but one of these had persistent antibody levels at follow-up. Pseudoviral neutralization activity was widespread among participants, did not decrease over time, and correlated with clinical antibody assays. Reinfection with SARS-CoV-2 was not observed among individuals with mild clinical COVID-19, while infections continued in a group without known prior infection. Spike and nucleocapsid COVID-19 antibodies were associated with almost all infections and persisted at stable levels for the study duration. IMPORTANCE This article demonstrates that people who have mild COVID-19 illnesses and produce antibodies are protected from reinfection for up to 6 months afterward. The antibodies that people produce in this situation are stable for up to 6 months as well. Clinical antibody assays correlate well with evidence of antibody-related viral neutralization activity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Coronavirus Nucleocapsid Proteins/immunology , Reinfection/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Adult , COVID-19/immunology , COVID-19 Testing , Female , Humans , Immunoassay , Male , Phosphoproteins/immunology , Prospective Studies , Reinfection/immunology , SARS-CoV-2/immunology
7.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Article in English | MEDLINE | ID: covidwho-1276013

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , SARS-CoV-2/pathogenicity , Virus Replication , Animals , Antibodies, Neutralizing , COVID-19/diagnostic imaging , COVID-19/pathology , Cricetinae , Humans , Immunogenicity, Vaccine , Lung/pathology , Mesocricetus , Mice , Spike Glycoprotein, Coronavirus/genetics , X-Ray Microtomography
8.
Am J Clin Pathol ; 155(2): 267-279, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-841691

ABSTRACT

OBJECTIVES: Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has experienced a changing landscape of available assays coupled with uncertainty surrounding performance characteristics. Studies are needed to directly compare multiple commercially available assays. METHODS: Residual serum samples were identified based on SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing, clinical test results, and collection dates. Serum samples were analyzed using assays from four different manufacturers: DiaSorin anti-SARS-CoV-2 S1/S2 IgG, EUROIMMUN anti-SARS-CoV-2 IgG ELISA, Roche Elecsys anti-SARS-CoV-2, and Siemens SARS-CoV-2 Total antibody assays. RESULTS: Samples from SARS-CoV-2 RT-PCR-positive patients became increasingly positive as time from symptom onset increased. For patients with latest sample 14 or more days after symptom onset, sensitivities reached 93.1% to 96.6%, 98.3%, and 96.6% for EUROIMMUN, Roche, and Siemens assays, respectively, which were superior to the DiaSorin assay at 87.7%. The specificity of Roche and Siemens assays was 100% and superior to DiaSorin and EUROIMMUN assays, which ranged from 96.1% to 97.0% and 86.3% to 96.4%, respectively. CONCLUSIONS: Laboratories should be aware of the advantages and limitations of serology testing options for SARS-CoV-2. The specificity and sensitivity achieved by the Roche and Siemens assays would be acceptable for testing in lower-prevalence regions and have the potential of orthogonal testing advantages if used in combination.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , High-Throughput Screening Assays/methods , SARS-CoV-2/immunology , Female , Humans , Male , Predictive Value of Tests , Sensitivity and Specificity
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