Lymphopenia as a Biological Predictor of Outcomes in COVID-19 Patients: A Nationwide Cohort Study

SIMPLE SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a major global health crisis. Owing to the rising number of cases and limited global resources, being able to predict patients with a severe disease course is crucial for the initial allocation of the limited medical resources. This study aimed to identify whether lymphopenia is a reliable prognostic marker for COVID-19 using Korean nationwide cohort. Lymphopenia and its severity levels may serve as reliable predictive factors for COVID-19 clinical outcomes including mortality, needs for intensive care, and oxygen requirements. Current study suggests that lymphopenia at the initial presentation of COVID-19 is associated with poor prognosis. ABSTRACT: We aimed to identify whether lymphopenia is a reliable prognostic marker for COVID-19. Using data derived from a Korean nationwide longitudinal cohort of 5628 COVID-19 patients, we identified propensity-matched cohorts (n = 770) with group I of severe lymphopenia (absolute lymphocyte counts [ALC]: <500/mm(3), n = 110), group II of mild-to-moderate lymphopenia (ALC: ≥500–<1000/mm(3), n = 330), and group III, no lymphopenia (ALC: ≥1000/mm(3), n = 330). A significantly higher mortality rate was associated with lymphopenia severity: 40% in group I, 22.7% in group II, and 13.0% in group III (p < 0.001). At 28 days, the estimated inferior overall survival associated with intensified lymphopenia: 62.7% in group I, 79.9% in group II, and 89.0% in group III (p < 0.001). Lymphopenia contributed significantly toward a greater need for interventions in all groups but at varying degrees: requirements of invasive ventilation, intensive oxygen supply, or adequate oxygen supply, respectively (p < 0.001). The lymphopenia intensity was independently associated with higher COVID-19 mortality in multivariable analysis; adjusted odds ratios of 5.63 (95% CI, 3.0–10.72), and 2.47 (95% CI, 1.5–4.13) for group I and group II, respectively. Lymphopenia and its severity levels may serve as reliable predictive factors for COVID-19 clinical outcomes; thus, lymphopenia may provide the prognostic granularity required for clinical use in the management of patients with COVID-19.