Insulin Resistance Predicts Severe Acute COVID-and Long COVID

ABSTRACT

Background: Obesity and diabetes are known risk factors for severe acute COVID-19. About half of individuals with obesity have insulin resistance (IR) , which may potentiate severe acute disease and/or predispose to long COVID. Methods: We identified 596 adults from Stanford hospital or clinics confirmed COVID-19+ by rtPCR and categorized according to severity of illness based on the NIH categories1. Pre-COVID predictors including BMI, fasting plasma glucose (FPG) , and triglyceride/HDL-cholesterol ratio (TG/HDL) as a surrogate2 for IR were ed from the EMR using the Stanford Research Repository Tools software. Follow-up surveys were administered via REDCap 2-4x in the first month and 1x per month for 1 year thereafter to assess symptom type and duration. Long COVID was defined as symptom duration > 30 days. Metabolic predictors of acute COVID-severity (BMI, FPG, TG/HDL) were evaluated via multiple linear regression adjusted for sex, age, ethnicity, and other metabolic predictors. A logistic regression to predict long COVID included all metabolic predictors along with age, sex, and ethnicity. Models were repeated with a stepwise approach to increase statistical power given the smaller number of participants with complete data. Results: Participants were 51±18 years of age, 49% female, and 62% racial and ethnic minorities. Mean BMI was 29.5±7.9 kg/m2. NIH illness severity was 7.9% asymptomatic, 37.2% mild, 25.9% moderate, 15.1% severe, and 13.9% critical. Diabetes, lung disease, and hypertension prevalence were 27%, 18%, and 34%, respectively. Mean follow-up was 94±99 and incidence of long COVID was 47.1%. BMI, FPG, and TG/HDL were independently associated with acute COVID-severity in the cohort as a whole (r=0.187, P<0.001;r=0.180, P=0.002;r=0.180, P=0.009) , while only TG/HDL was associated with long COVID (r=0.173, p=0.013) . Conclusions: Findings suggest that IR, independent of sex, age, ethnicity, obesity and hyperglycemia, confers increased risk for both severe acute COVID-and long COVID.