Science

Yan Xie, Ziyad Al-Aly

Background
There is growing evidence suggesting that beyond the acute phase of SARS-CoV-2 infection, people with COVID-19 could experience a wide range of post-acute sequelae, including diabetes. However, the risks and burdens of diabetes in the post-acute phase of the disease have not yet been comprehensively characterised. To address this knowledge gap, we aimed to examine the post-acute risk and burden of incident diabetes in people who survived the first 30 days of SARS-CoV-2 infection.

Methods
In this cohort study, we used the national databases of the US Department of Veterans Affairs to build a cohort of 181280 participants who had a positive COVID-19 test between March 1, 2020, and Sept 30, 2021, and survived the first 30 days of COVID-19; a contemporary control (n=4 118 441) that enrolled participants between March 1, 2020, and Sept 30, 2021; and a historical control (n=4286911) that enrolled participants between March 1, 2018, and Sept 30, 2019. Both control groups had no evidence of SARS-CoV-2 infection. Participants in all three comparison groups were free of diabetes before cohort entry and were followed up for a median of 352 days (IQR 245–406). We used inverse probability weighted survival analyses, including predefined and algorithmically selected high dimensional variables, to estimate post-acute COVID-19 risks of incident diabetes, antihyperglycaemic use, and a composite of the two outcomes. We reported two measures of risk: hazard ratio (HR) and burden per 1000 people at 12 months.

Findings
In the post-acute phase of the disease, compared with the contemporary control group, people with COVID-19 exhibited an increased risk (HR 1·40, 95% CI 1·36–1·44) and excess burden (13·46, 95% CI 12·11–14·84, per 1000 people at 12 months) of incident diabetes; and an increased risk (1·85, 1·78–1·92) and excess burden (12·35, 11·36–13·38) of incident antihyperglycaemic use. Additionally, analyses to estimate the risk of a composite endpoint of incident diabetes or antihyperglycaemic use yielded a HR of 1·46 (95% CI 1·43–1·50) and an excess burden of 18·03 (95% CI 16·59–19·51) per 1000 people at 12 months. Risks and burdens of post-acute outcomes increased in a graded fashion according to the severity of the acute phase of COVID-19 (whether patients were non-hospitalised, hospitalised, or admitted to intensive care). All the results were consistent in analyses using the historical control as the reference category.

Interpretation
In the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre- pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.