Abstract: Irish Journal of Medical Science (1971 -) https://doi.org/10.1007/s11845-022-02952-9 ORIGINAL ARTICLE A combined role for low vitamin D and low albumin circulating levels as strong predictors of worse outcome in COVID‑19 patients Gianfranco Sanson1 · Amedeo De Nicolò2 · Verena Zerbato3 · Ludovica Segat4 · Raffaella Koncan4 Stefano Di Bella1,3,8 · Jessica Cusato2 · Alessandra di Masi5 · Andrea Palermo6 · Pietro Caironi7 · Pierlanfranco D’Agaro4 · Roberto Luzzati1,3 · Antonio D’Avolio2 · Received: 28 August 2021 / Accepted: 8 February 2022 © The Author(s) 2022 Abstract Purpose We aimed to assess the combined role of vitamin D and albumin serum levels as predictors of COVID-19 disease progression. Methods We conducted a prospective observational study on adult patients hospitalized for SARS-CoV-2 pneumonia (March–September 2020). Vitamin D and albumin serum levels were measured on admission. These variables were categorized in albumin < 3.5 or ≥ 3.5 g/dL and vitamin D < 30 ng/mL or ≥ 30 ng/mL. We excluded patients with known bone diseases, renal failure, hypercalcemia and/or treated with antiepileptic drugs and steroids, and patients who received previous vitamin D supplementation. A composite outcome including any ventilatory support, P ­ aO2/FiO2 ratio, and 60-day mortality was defined. Results Sixty-nine patients were enrolled, of whom 50% received non-invasive (NIV) or invasive mechanical ventilation (IMV), 10% died, whereas 89% and 66% presented low albumin and low vitamin D serum levels, respectively. No correlation between vitamin D and albumin levels was found. In multivariable logistic regression analyses adjusted for sex and age-corrected comorbidities, patients having albumin < 3.5 g/dL and vitamin D < 30 ng/mL showed a significant increased risk for all study outcomes, namely NIV/IMV (OR 3.815; 95% CI 1.122–12.966; p = 0.032), NIV/IMV or death (OR 3.173; 95% CI 1.002–10.043; p = 0.049) and ­PaO2/FIO2 ≤ 100 (OR 3.410; 95% CI 1.138–10.219; p = 0.029). Conclusion The measurement of both vitamin D and serum albumin levels on COVID-19 patients’ admission, and their combined evaluation, provides a simple prognostic tool that could be employed to guide prompt clinical decisions. Keywords COVID-19 · Human serum albumin · SARS-CoV-2 · Vitamin D