Interaction Effect Between Hemoglobin and Hypoxemia on COVID-19 Mortality: an observational study from Bogotá, Colombia

Andrés Felipe Patiño-Aldana,1 Ángela María Ruíz Sternberg,1 Ángela María Pinzón Rondón,1 Nicolás Molano-Gonzalez,1 David Rene Rodriguez Lima1,2 1Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia; 2CIMED, Hospital Universitario Mayor - Méderi, Bogotá, ColombiaCorrespondence: Andrés Felipe Patiño-Aldana, Email andresf.patino@urosario.edu.coPurpose: We aimed to assess the effect of hemoglobin (Hb) concentration and oxygenation index on COVID-19 patients’ mortality risk.Patients and Methods: We retrospectively reviewed sociodemographic and clinical characteristics, laboratory findings, and clinical outcomes from patients admitted to a tertiary care hospital in Bogotá, Colombia, from March to July 2020. We assessed exploratory associations between oxygenation index and Hb concentration at admission and clinical outcomes. We used a generalized additive model (GAM) to evaluate the observed nonlinear relations and the classification and regression trees (CART) algorithm to assess the interaction effects.Results: We included 550 patients, of which 52% were male. The median age was 57 years old, and the most frequent comorbidity was hypertension (29%). The median value of SpO2/FiO2 was 424, and the median Hb concentration was 15 g/dL. The mortality was 15.1% (83 patients). Age, sex, and SpO2/FiO2, were independently associated with mortality. We described a nonlinear relationship between Hb concentration and neutrophil-to-lymphocyte ratio with mortality and an interaction effect between SpO2/FiO2 and Hb concentration. Patients with a similar oxygenation index had different mortality likelihoods based upon their Hb at admission. CART showed that patients with SpO2/FiO2 < 324, who were less than 81 years with an NLR > 9.9, and Hb > 15 g/dl had the highest mortality risk (91%). Additionally, patients with SpO2/FiO2 > 324 but Hb of < 12 g/dl and a history of hypertension had a higher mortality likelihood (59%). In contrast, patients with SpO2/FiO2 > 324 and Hb of > 12 g/dl had the lowest mortality risk (9%).Conclusion: We found that a decreased SpO2/FiO2 increased mortality risk. Extreme values of Hb, either low or high, showed an increase in the likelihood of mortality. However, Hb concentration modified the SpO2/FiO2 effect on mortality; the probability of death in patients with low SpO2/FiO2 increased as Hb increased.Keywords: hypoxia, erythrocytosis, acute respiratory infection, SARS-CoV-2, neutrophil-to-lymphocyte ratio, generalized additive model, classification and regression tree, inflammation, altitude, acute lung injury