Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Ijaz, Samreen; Dicks, Steve; Jegatheesan, Keerthana; Parker, Eleanor; Katsanovskaja, Ksenia; Vink, Elen; McClure, Myra O.; Shute, Justin; Hope, Joshua; Cook, Nicola; Cherepanov, Peter; Turtle, Lance; Paxton, William A.; Pollakis, Georgios; Ho, Antonia; Openshaw, Peter; Baillie, J Kenneth; Semple, Malcolm G; Tedder, Richard S.

doi:10.1016/j.jinf.2022.05.033

Cited by 6 publications

(9 citation statements)

References 30 publications

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“…Participants gave their written informed consent to take part in the study. Between May 11, 2020, and May 24, 2022, 320 participants aged 14-87 years (median 31, IQR [25][26][27][28][29][30][31][32][33][34][35][36][37]) were recruited and followed for up to 837 days (median 155, IQR [58-277]). Two individuals lacked age information: 245 were males and 75 were females.…”

Section: Study Design and Populationmentioning

confidence: 99%

“…Multiple viral proteins (29,30) elicit prompt and longlasting immunity that persists for several months (31)(32)(33). SARS-CoV-2-directed S-and N-IgG, -IgM, and -IgA antibody profiles have guided inference of the serological response to COVID-19 and provided insight into the relevance of targeting the Spike-protein for vaccine design (34,35). Using data from European cohorts, mathematical modellers predicted the persistence of functional Spike and RBDdirected antibodies 465 days post-infection and faster decay of Ndirected antibodies, providing data that inform vaccination and serosurveillance strategies (36).…”

Section: Introductionmentioning

confidence: 99%

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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

Serwanga

Ankunda²,

Sembera³

et al. 2023

Front. Immunol.

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IntroductionUnderstanding 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.MethodsHere, 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.ResultsDuring 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.DiscussionLower 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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Section: Study Design and Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Serwanga

Ankunda²,

Sembera³

et al. 2023

Front. Immunol.

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“…The SARS-CoV-2 S1 antigen (spanning Wuhan-Hu-1 SARS-CoV-2 Spike residues 1–530, C-terminal twin Strep tag) ( 41 , 42 ) was produced and gifted by The Francis Crick Institute and conjugated to HRP using the Bio-Rad LYNX HRP conjugation kit, in accordance with the manufacturer’s instructions. Recombinant NP antigens from seasonal coronavirus NL63, OC43, HKU1 and 229E were used to block non-specific NP responses as previously described ( 43 ). These proteins were produced in Escherichia coli with N-terminal hexahistidine-SUMO and C-terminal Twin Strep tags and purified by tandem immobilised metal and StrepTactin ® affinity chromatography.…”

Section: Methodsmentioning

confidence: 99%

“…The SARS-CoV-2 full length spike glycoprotein (Spike/amino acids 1-1211; His-tag) and the nucleoprotein (NP) conjugated to Horseradish peroxidase (HRP) were purchased from The Native Antigen Company (Kidlington, Oxford, UK). The SARS-CoV-2 S1 antigen (spanning Wuhan-Hu-1 SARS-CoV-2 Spike residues 1-530, C-terminal twin Strep tag) (41,42) was produced and gifted by The Francis Crick Institute and conjugated to HRP using the Bio-Rad LYNX HRP conjugation kit, in accordance with the manufacturer's instructions. Recombinant NP antigens from seasonal coronavirus NL63, OC43, HKU1 and 229E were used to block non-specific NP responses as previously described (43).…”

Section: Anti-sars-cov-2 S1 Spike and Np Igm And Igg Capture Elisasmentioning

confidence: 99%

SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

Parker

Thomas²,

Roper³

et al. 2023

Front. Immunol.

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The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

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“…We read with interest the article by Ijaz et al regarding the mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid (GCF), and its linkage to disease severity in hospitalised COVID-19 patients. The authors report some evidence that higher levels of antibody in GCF in the first 14 days post symptom onset were associated with severe disease and poor outcome ( 1 ). The utility of less invasive, non-venous analytes has been increasingly recognised during the global pandemic.…”

mentioning

confidence: 99%

Faecal calprotectin as a potential biomarker of disease severity in SARS-CoV-2 infection

O'Morain

Stack

Doherty

et al. 2022

Journal of Infection

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Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Cited by 6 publications

References 30 publications

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

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

SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

Faecal calprotectin as a potential biomarker of disease severity in SARS-CoV-2 infection

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