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1.
Cell ; 185(6): 1025-1040.e14, 2022 03 17.
Article in English | MEDLINE | ID: covidwho-1649487

ABSTRACT

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Germinal Center , Humans , RNA, Messenger , SARS-CoV-2 , Vaccination
2.
Emerg Infect Dis ; 27(10): 2720-2723, 2021.
Article in English | MEDLINE | ID: covidwho-1486743

ABSTRACT

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , Humans , Mutation , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
3.
Diagn Microbiol Infect Dis ; 101(4): 115517, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1347571

ABSTRACT

Dengue and COVID-19 cocirculation presents a diagnostic conundrum for physicians evaluating patients with acute febrile illnesses, both in endemic regions and among returning travelers. We present a case of a returning traveler from Pakistan who, following repeated negative SARS-CoV-2 tests, was found to have a Dengue virus serotype 2 infection.


Subject(s)
COVID-19/diagnosis , Dengue/diagnosis , SARS-CoV-2 , Adult , COVID-19/epidemiology , California/epidemiology , Dengue/epidemiology , Dengue Virus/classification , Dengue Virus/genetics , Female , Genome, Viral , Humans , Pakistan/epidemiology , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Serogroup , Travel
4.
Emerg Infect Dis ; 27(10): 2720-2723, 2021.
Article in English | MEDLINE | ID: covidwho-1323073

ABSTRACT

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , Humans , Mutation , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
5.
Clin Chem ; 67(7): 977-986, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1132473

ABSTRACT

BACKGROUND: Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results. METHODS: Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis. RESULTS: There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] vs 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] vs 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6. CONCLUSION: Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoglobulin G/blood , Nucleocapsid/immunology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Adult , Area Under Curve , COVID-19/virology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , ROC Curve , Reagent Kits, Diagnostic , Retrospective Studies , SARS-CoV-2/isolation & purification
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