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Immunoglobulin G glycome and severity of COVID-19: more likely a quantification of bias than a true association. A comment on Petrović et al., "Composition of the immunoglobulin G glycome associates with the severity of COVID-19"

A recent manuscript (Petrović et al. 2020) suggested an association between certain aspects of the total immunoglobulin G (IgG) glycosylation pattern and severity of the disease in hospitalized COVID-19 patients. More specifically, the authors claimed that their data supported a conclusion about “cross-sectional association” (Petrović et al. 2020) between higher percentage of bisecting N-acetlyglucosamine (GlcNAc) in the total IgG N-glycome and less severe disease (or, in reverse, between lower GlcNAc percentage and a “severe” disease, as opposed to “mild”). Comments on biological plausibility or on potential practical relevance of the IgG glycome research in the COVID-19 setting are beyond our scope—we draw the attention to methodological flaws (apart from a clearly superior bioanalytics) of the manuscript in question due to which we consider the reported “effects” by far more likely to represent quantification of bias than of a true association. We elaborate our view by addressing potential “doors” through which bias could have been introduced (Altman 1994), i.e., design, analysis, reporting and interpretation. We then use the reported data (Petrović et al. 2020) to reconstruct information about uncertainty that was not reported, reanalyze data to illustrate this uncertainty, and subject reported effects to the analysis of sensitivity to unmeasured confounding.

COVID-19 ; immunoglobulin

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