Preprint Mass-Standardised IgG Response to Fourteen [Spike Protein] variants and Antibody Subclass analysis for IgG subclasses and IgE…, 2026, Elangovan+

[SNT Gatchaman]

Mass-Standardised IgG Response to Fourteen SARS-CoV-2 Spike Protein variants and Antibody Subclass analysis for IgG subclasses and IgE for a Long COVID Patient Cohort

Spoiler: Authors

Abishek Elangovan; Daniel Harper; Philip James-Pemberton; Shivali Kohli; Ciara Watson; Andrew Shaw

A multivariant total subclass analysis has been performed for a control cohort (n=15) and a long COVID patient cohort (n=15) measuring the IgG1, IgG2, IgG3, IgG4 and IgE response to the following 14 variants of SARS-CoV-2: Wuhan, Alpha, Delta, BA.1, BA.2, BA.5, EG.5.1, XBB.1.5, BA.2.75, CH.1.1, BA.2.12.1, BQ.1.1, JN.1, and KP.3.

Significant differences (p < 0.05 and p < 0.005) between concentrations of IgG subclasses by variant were found in 24% of variants and in mean-normalised distributions. The medians of the mean-normalised distributions were significantly lower for IgG1 (p < 0.05) in long COVID patients compared with controls, and significantly higher (p < 0.005) for levels of IgG3, IgG4 and IgE for long COVID patients.

A preliminary diagnostics classification analysis performed by variation of the mean-normalised upper and lower percentiles symmetrically for IgG3 showed a long COVID diagnostic sensitivity of 80%, and specificity of 80% for the 60th percentile threshold of the control cohort.

Three types of long COVID can be identified: patients with at least one variant below the threshold (hypo-immune), patients with at least one variant above the threshold (hyperimmune) and patients with IgG3 levels within the reference range. The multivariant subclass spectrum indicates IgG4 and IgE elevations due to potential chronic antigen exposure from persistent virus or autoimmunity and may indicate potential therapeutic interventions.


Web | DOI | PDF | Preprint: MedRxiv | Open Access

 

[SNT Gatchaman]

Funding
The project was funded by Attomarker Ltd, the alumni of the University of Exeter donating to the COVID appeal in Prof Shaw’s group, and the patients taking the COVID Antibody Spectrum Test. Abishek Elangovan worked on the study as part of their undergraduate studies at the University of Exeter.

Declaration of Interests
Prof Shaw is the Founder, CEO and Director of Attomarker Ltd, a spin-out company from his research group at the University of Exeter, which is also a shareholder.

Thread for the company at Exeter firm excited over long Covid test success [BBC News].

 

[hotblack]

Can we be sure these shifts observed are real and identifiable? I don’t know enough about this or the techniques but seem to remember people being unsure about general fluctuations in antibodies?

They seem to jump to the persistent virus or autoimmunity angle, could this be just as much due to or linked with the sort of immune changes that have been hypothesised in other papers?

 

[Jonathan Edwards]

Can we be sure these shifts observed are real and identifiable?

I think this study suffers from all the usual sort of circular arguments about discriminatory tests. The comment about persistent virus and autoimmunity is just pasting in received dogma.

Differences in IgG class responses might be a clue to a mechanism but Long Covid is so vague and generalisation beyond Covid is so uncertain that I cannot get excited about this.