Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients

AimTo investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients.MethodsWe retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission.ResultsThe median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index).ConclusionRDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a systemic infectious disease usually presenting with fever and respiratory symptoms (1). Although the most frequent serious manifestation of COVID-19 is pneumonia, the disease has been associated with cardiovascular, neurological, and gastrointestinal symptoms (2). Systemic inflammatory response mediated by high interleukin-6 concentrations induced by SARS-CoV-2 infection is associated with more severe clinical presentation, respiratory deterioration, and death (3,4). The presence of prior chronic comorbidities substantially affects the survival of COVID-19 patients (1).Anisocytosis, ie, unequal red blood cells (RBC) size, is a sensitive marker of distress in erythropoiesis or RBC destruction. It can be induced by various metabolic and inflammatory stimuli, nutrient deficiencies, infections, spleen disorders, and specific drugs interfering with RBC production (5). Anisocytosis can be quantified as a coefficient of variation of mean cell volume termed red blood cell distribution width (RDW), which is obtained by automatic cell counters. Higher RDW levels have recently gained attention as they are uniformly associated with unfavorable presentation and inferior outcomes in many chronic metabolic and malignant diseases (6-12). More severe clinical presentation and higher mortality rates were also found in COVID-19 patients with higher RDW levels (13-16). However, an association of RDW with other clinical outcomes in hospitalized COVID-19 patients, as well as the relationship with increased mortality in the context of other established prognostic scores, are not well defined. Thus, we aimed to investigate clinical and prognostic significance of RDW in a large cohort of hospitalized COVID-19 patients from our institution. We hypothesized that RDW was associated with more severe COVID-19 on admission and higher death rate.