Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C)
Samuel Soff, Yun Jae Yoo, Carolyn Bramante, Jane E B Reusch, Jared Davis Huling, Margaret A Hall, Daniel Brannock, Til Sturmer, Zachary Butzin-Dozier, Rachel Wong, Dr Richard Moffitt
BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2024-004536
Introduction Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear. Objective Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).
Research design and methods We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30-180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control. Results Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to <10% (OR 1.20, 95% CI 1.02 to 1.41) and ≥10% (OR 1.40, 95% CI 1.14 to 1.72) compared with those with HbA1c 6.5% to <8%. This association was not seen in the COVID-negative group. Higher HbA1c levels were associated with increased risk of Long COVID symptoms, especially respiratory and brain fog. There was no association between HbA1c levels and risk of death within 30-180 days following COVID-19. NLP identified more patients with Long COVID symptoms compared with diagnosis codes. Conclusion Poor glycemic control (HbA1c≥8%) in people with T2D was associated with higher risk of Long COVID symptoms 30-180 days following COVID-19. Notably, this risk increased as HbA1c levels rose. However, this association was not observed in patients with T2D without a history of COVID-19. An NLP-based definition of Long COVID identified more patients than diagnosis codes and should be considered in future studies. ⇒ Clinicians should be aware of the increased risk of Long COVID in patients with poor glycemic control, especially respiratory and brain fog symptoms. Additionally, this study highlights that only textual data from clinical notes contained sufficient information to capture Long COVID in these patients, indicating the potential insensitivity of diagnosis codes in identifying Long COVID.
Contributors SS, RW, and RM conceived the study. SS and YJY performed the analysis. JEBR and RW provided clinical expertise and reviewed/edited the manuscript. RM, MAH, TS, ZB-D, JDH and DB provided statistical or analytical expertise and reviewed/edited the manuscript. CB provided expertise on diabetes and obesity. SS drafted the manuscript and is the guarantor of this work, and as such had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Disclaimer The N3C Publication Committee confirmed that this manuscript (MSID:1915.021) is in accordance with N3C data use and attribution policies; however, this content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the N3C program. Competing interests TS receives funding and support from the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Takeda, AbbVie, Boehringer Ingelheim, Astellas, and Sarepta) and owns stock in Novartis, Roche, and Novo Nordisk. JEBR has affiliations with or receives funding from Springer Nature Switzerland-Exercise Book, Medtronic Diabetes, and AstraZeneca.
Patient consent for publication Not applicable. Ethics approval N3C Attribution. The analyses..
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"abstract": "<jats:sec><jats:title>Introduction</jats:title><jats:p>Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).</jats:p></jats:sec><jats:sec><jats:title>Research design and methods</jats:title><jats:p>We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30–180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to <10% (OR 1.20, 95% CI 1.02 to 1.41) and ≥10% (OR 1.40, 95% CI 1.14 to 1.72) compared with those with HbA1c 6.5% to <8%. This association was not seen in the COVID-negative group. Higher HbA1c levels were associated with increased risk of Long COVID symptoms, especially respiratory and brain fog. There was no association between HbA1c levels and risk of death within 30–180 days following COVID-19. NLP identified more patients with Long COVID symptoms compared with diagnosis codes.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Poor glycemic control (HbA1c≥8%) in people with T2D was associated with higher risk of Long COVID symptoms 30–180 days following COVID-19. Notably, this risk increased as HbA1c levels rose. However, this association was not observed in patients with T2D without a history of COVID-19. An NLP-based definition of Long COVID identified more patients than diagnosis codes and should be considered in future studies.</jats:p></jats:sec>",
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