Microvascular disease in diabetes and severe COVID-19 outcomes

We read with great interest the Article by Stuart McGurnaghan and colleagues¹ on the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes compared with people without diabetes in Scotland. We would like to comment on and emphasise the importance of microvascular complications and indices of diabetic microangiopathy, such as retinopathy, albuminuria, and advanced diabetic kidney disease, as risk factors for more severe outcomes of COVID-19.

Microvascular disease has been associated with worse outcomes in people with diabetes admitted to hospital for COVID-19.2, 3 Pre-existing endothelial dysfunction and diffuse microangiopathy, particularly in the pulmonary microcirculation, may help to explain worse outcomes in people with diabetes.3, 4 McGurnaghan and colleagues found a significantly higher risk of fatal or critical care unit-treated COVID-19 in people with diabetes and albuminuria, with an odds ratio of 1·352 (95% CI 1·155–1·583; p=0·0002) and 1·922 (1·519–2·430; p<0·0001) for microalbuminuria and macroalbuminuria compared with people with diabetes and normoalbuminuria. However, albuminuria status was unknown for 470 (43·4%) of 1082 people with fatal or critical care unit-treated COVID-19 and for 120 305 (37·8%) of 318 267 without fatal or critical care unit-treated COVID-19. These missing data might have affected why albuminuria, a biomarker of endothelial damage, was not selected in the final multivariable risk prediction model. Moreover, the strong biological association and probable statistical collinearity between microvascular complications and duration of diabetes could be another explanation why albuminuria and retinopathy were not included in the final risk prediction model. Whether imputation was used for albuminuria measurements or categories is unclear. Furthermore, it is not reported if there was any significant association observed between albuminuria results entered as a continuous variable and worse COVID-19 outcomes. The authors also observed that estimated glomerular filtration rate was significantly lower in people with fatal or critical care unit-treated COVID-19, even after adjustment for age and duration of diabetes. It would be valuable to know whether more advanced stages of chronic kidney disease were associated with worse outcomes, as observed in another study.⁵

Pre-existing pulmonary endothelial dysfunction and microangiopathy can affect gas exchange.⁴ Homoeostasis, through capillary recruitment, will then no longer be achieved in severe COVID-19, contributing to the severity of adult respiratory distress syndrome in patients with COVID-19.⁶ Retinopathy or albuminuria may represent a burden of pre-existing pulmonary microangiopathy. Further research is needed to assess the role of microvascular disease in diabetes and severe COVID-19 outcomes.