BMJ Open Diabetes Research & Care (Feb 2025)

Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C)

  • ,
  • Jane E B Reusch,
  • Rachel Wong,
  • Nasia Safdar,
  • Harold Lehmann,
  • Brijesh Patel,
  • Til Stürmer,
  • Hongfang Liu,
  • Peter Robinson,
  • Elaine Hill,
  • Richard Moffitt,
  • Justin Guinney,
  • Joel Gagnier,
  • Cavin Ward-Caviness,
  • Noha Sharafeldin,
  • Justin Starren,
  • Amit Saha,
  • Lesley Cottrell,
  • Melissa A Haendel,
  • Margaret A Hall,
  • Vignesh Subbian,
  • Kristin Kostka,
  • Farrukh M Koraishy,
  • Andrew E Williams,
  • Robert Hurley,
  • Steve Johnson,
  • Usman Sheikh,
  • Rishi Kamaleswaran,
  • Christopher Dillon,
  • Michele Morris,
  • Randeep Jawa,
  • Hemalkumar Mehta,
  • Benjamin Bates,
  • Tellen D Bennett,
  • Nabeel Qureshi,
  • Katie Rebecca Bradwell,
  • Federico Mariona,
  • Adam B Wilcox,
  • Adam M Lee,
  • Alexis Graves,
  • Amin Manna,
  • Amy Olex,
  • Andrea Zhou,
  • Andrew Southerland,
  • Andrew T Girvin,
  • Anita Walden,
  • Anjali A Sharathkumar,
  • Benjamin Amor,
  • Brian Hendricks,
  • Caleb Alexander,
  • Carolyn Bramante,
  • Charisse Madlock-Brown,
  • Christine Suver,
  • Christopher Chute,
  • Chunlei Wu,
  • Clare Schmitt,
  • Cliff Takemoto,
  • Dan Housman,
  • Davera Gabriel,
  • David A Eichmann,
  • Diego Mazzotti,
  • Eilis Boudreau Don Brown,
  • Elizabeth Zampino,
  • Emily Carlson Marti,
  • Emily R Pfaff,
  • Evan French,
  • Fred Prior,
  • George Sokos,
  • Greg Martin,
  • Heidi Spratt,
  • Hythem Sidky,
  • JW Awori Hayanga,
  • Jami Pincavitch,
  • Jaylyn Clark,
  • Jeremy Richard Harper,
  • Jessica Islam,
  • Jin Ge,
  • Joel H Saltz,
  • Joel Saltz,
  • Johanna Loomba,
  • John Buse,
  • Jomol Mathew,
  • Joni L Rutter,
  • Julie A McMurry,
  • Karen Crowley,
  • Kellie M Walters,
  • Ken Wilkins,
  • Kenneth R Gersing,
  • Kenrick Dwain Cato,
  • Kimberly Murray,
  • Lavance Northington,
  • Lee Allan Pyles,
  • Leonie Misquitta,
  • Lili Portilla,
  • Mariam Deacy,
  • Mark M Bissell,
  • Marshall Clark,
  • Mary Emmett,
  • Mary Morrison Saltz,
  • Matvey B Palchuk,
  • Meredith Adams,
  • Meredith Temple-O'Connor,
  • Michael G Kurilla,
  • Nicole Garbarini,
  • Ofer Sadan,
  • Patricia A Francis,
  • Penny Wung Burgoon,
  • Rafael Fuentes,
  • Rebecca Erwin-Cohen,
  • Richard A Moffitt,
  • Richard L Zhu,
  • Robert T Miller,
  • Saiju Pyarajan,
  • Sam G Michael,
  • Samuel Bozzette,
  • Sandeep Mallipattu,
  • Satyanarayana Vedula,
  • Scott Chapman,
  • T Shawn,
  • Soko Setoguchi O'Neil,
  • Stephanie S Hong,
  • Tiffany Callahan,
  • Umit Topaloglu,
  • Valery Gordon,
  • Warren A Kibbe,
  • Wenndy Hernandez,
  • Will Beasley,
  • Will Cooper,
  • William Hillegass,
  • Xiaohan Tanner Zhang,
  • Samuel Soff,
  • Yun Jae Yoo,
  • Jared Davis Huling,
  • Daniel Brannock,
  • Zachary Butzin-Dozier,
  • Alfred Jerrod Anzalone,
  • Philip RO. Payne,
  • Rena Patel

DOI
https://doi.org/10.1136/bmjdrc-2024-004536
Journal volume & issue
Vol. 13, no. 1

Abstract

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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.