The enduring effect of the COVID-19 pandemic on diabetes

The acute clinical manifestations of COVID-19 have been well characterized1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

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 181 280 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=4 286 911) 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. Funding US Department of Veterans Affairs and the American Society of Nephrology.