Patients with low ALT levels are at increased risk for severe COVID-19.

Introduction: Frailty is a known risk factor for many diseases, including COVID-19. However, many frail patients are undiagnosed as the diagnosis can be cumbersome. Alanine transaminase (ALT) is found not only in the liver but also in the muscle tissue, and multiple studies show that frail sarcopenic patients have lower ALT. Frail patients are at increased risk for severe COVID-19. We evaluated the association between pre-infection low ALT and the risk for severe COVID-19. Methods: We collected data regarding all subjects tested for SARS-CoV-2 between 1 March 2020 and 31 December 2021 from a national state-mandatory HMO in Israel, serving more than 1.3 million patients. Clinical and laboratory data were collected, including ALT from the year prior to infection. Severe COVID-19 was defined either as death, ICU admission, or ≥10 hospitalization days. Patients with low ALT (ALT ≤ 10 IU/l) were compared with patients with normal ALT (11-40 IU/l). Patients younger than 18 years with a diagnosis of liver disease and with ALT > 40 IU/l were excluded. Results: During the study period, 58,961 patients tested positive for SARS-CoV-2. The patients in the low ALT group were younger (40.53 vs. 42.73, p < 0.001), less likely to be males (12.3 vs. 38.7%, p < 0.001), and had lower BMI (25.97 vs. 27.15, p < 0.001). The patients in the low ALT group had higher mortality (2.36 vs. 0.57%, p < 0.001), more ICU hospitalizations (0.49 vs. 0.41%, p = 0.47), and more prolonged hospitalizations [2.63% (95% CI 2-3.2%) vs. 0.98% (95% CI 0.86-1.1%) p < 0.001]. In multivariate logistic regression analyses, low ALT was associated with an increased risk of severe COVID-19, with increased mortality (OR 1.88, 95% CI 1.37-2.56) and prolonged hospitalization (OR 1.78, 95% CI 1.33-2.35). Conclusion: Low ALT level prior to infection is a significant risk factor for morbidity and mortality from COVID-19 infection. Further studies are warranted to address treatment options for this population.