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IntroductionFrailty 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.MethodsWe 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.ResultsDuring 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 ConclusionLow 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.</p