We thank Antonella Corcillo and colleagues for their interest in our Article.1 We fully agree with them on the importance of the association between microvascular disease and severe COVID-19 and its manifestation as associations with reduced estimated glomerular filtration rate (eGFR), albuminuria, and retinopathy. We also agree that the role of endothelial dysfunction in microvascular disease in diabetes suggests a common mechanism for the association with severe COVID-19. Indeed, in preliminary drafts from our Article we discussed this point, but space requirements meant that it was not included in the final version. Indeed, there is increasing recognition of the involvement of endothelial damage and microvascular dysfunction in COVID-19.2 Endothelial dysfunction and microvascular disease are common in diabetes.3 Albuminuria, reduced renal function, and retinopathy are all manifestations of endothelial damage and microvascular disease and all were associated with severe COVID-19 in our study. Regarding whether more advanced stages of chronic kidney disease were associated with worse COVID-19 outcomes, as observed in several studies,4 we note that this association is reported in Supplementary Table 6 of the appendix of our Article where we show that an eGFR of less than 30 mL/min per 1·73 m2 or being on renal replacement therapy was associated with a 2·37 times increased risk of severe COVID-19.1
As Corcillo and colleagues note, albuminuria was not selected in the prediction model. Missing values were imputed but, as Corcillo and colleagues also point out, collinearity with other variables can mean that strongly associated variables do not get selected. Because of the very strong association between albuminuria and reduced eGFR, and because eGFR was selected, the fact that albuminuria was not is unsurprising. As we note in our Article, “The variables retained in the model are those that are the most predictive and not necessarily causal”.1
Acknowledgments
HMC reports grants and personal fees from Eli Lilly and Novo Nordisk; grants from AstraZeneca, Regeneron, and Pfizer; institutional fees from Novartis and Sanofi Aventis; and being a shareholder with Roche Pharmaceuticals. All other authors declare no competing interests.
References
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