Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months
Copyright © 2023 Serwanga, Ankunda, Sembera, Kato, Oluka, Baine, Odoch, Kayiwa, Auma, Jjuuko, Nsereko, Cotten, Onyachi, Muwanga, Lutalo, Fox, Musenero, Kaleebu and The COVID-19 Immunoprofiling Team..
Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines.
Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months.
Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout.
Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 08., Seite 1152522 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Serwanga, Jennifer [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.04.2023 Date Revised 20.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1152522 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Serwanga, Jennifer |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 04.04.2023 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Serwanga, Ankunda, Sembera, Kato, Oluka, Baine, Odoch, Kayiwa, Auma, Jjuuko, Nsereko, Cotten, Onyachi, Muwanga, Lutalo, Fox, Musenero, Kaleebu and The COVID-19 Immunoprofiling Team. | ||
| 520 | |a Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines | ||
| 520 | |a Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months | ||
| 520 | |a Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout | ||
| 520 | |a Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings | ||
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| 700 | 1 | |a Ankunda, Violet |e verfasserin |4 aut | |
| 700 | 1 | |a Sembera, Jackson |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Laban |e verfasserin |4 aut | |
| 700 | 1 | |a Oluka, Gerald Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Baine, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Odoch, Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Kayiwa, John |e verfasserin |4 aut | |
| 700 | 1 | |a Auma, Betty Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Jjuuko, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Nsereko, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Cotten, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Onyachi, Nathan |e verfasserin |4 aut | |
| 700 | 1 | |a Muwanga, Moses |e verfasserin |4 aut | |
| 700 | 1 | |a Lutalo, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Fox, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Musenero, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Kaleebu, Pontiano |e verfasserin |4 aut | |
| 700 | 0 | |a COVID-19 Immunoprofiling Team |e verfasserin |4 aut | |
| 700 | 1 | |a Namubiru, Patricia |e investigator |4 oth | |
| 700 | 1 | |a Akoli, Hermilia Christine |e investigator |4 oth | |
| 700 | 1 | |a Mugaba, Susan |e investigator |4 oth | |
| 700 | 1 | |a Nalumansi, Amina |e investigator |4 oth | |
| 700 | 1 | |a Odoch, Geoffrey |e investigator |4 oth | |
| 700 | 1 | |a Freddie, Kibengo |e investigator |4 oth | |
| 700 | 1 | |a Mwesigwa, Deus |e investigator |4 oth | |
| 700 | 1 | |a Katende, Joseph Ssebwana |e investigator |4 oth | |
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