Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity

Glen Huang; Alex J. Kovalic; Christopher J. Graber


Emerging Infectious Diseases. 2020;26(8):1839-1841. 

In This Article


Pooled data across early studies validate a significant correlation between elevated leukocyte count and decreased lymphocyte count among patients with severe cases of COVID-19 compared with those with mild cases. Why lymphopenia is associated with severe illness remains unclear. It has been hypothesized that this association could result from direct lymphocyte infection, destruction of lymphatic tissue, inflammation leading to lymphocyte apoptosis, or inhibition of lymphocytes by metabolic disorders such as lactic acidosis.[12] Lymphopenia as a marker of severity does not seem to be specific to COVID-19; it has been used to prognosticate other viral pneumonias such as influenza.[13] Neutrophilia may be more specific to severe disease than leukocytosis, but neutrophil count was not uniformly reported across the studies included in our analysis.

Despite our findings regarding clinical characteristics of severe COVID-19, our study had several limitations. First, our literature search found an expected paucity of data surrounding this topic because published characterizations of patients with COVID-19 remain minimal. More COVID-19 data from other nations and patient populations will aid in the comparison and validation of our clinical findings. Second, we noted significant heterogeneity in both the leukocyte and lymphocyte analyses. This phenomenon probably resulted from the small sample size, limited and early data, and skewed representation of the patient population. Third, the definitions of severe cases were somewhat inconsistent across these studies, varying from acute hypoxic respiratory failure to requiring mechanical ventilation. This variability could further compound the heterogeneity found across these studies. Last, only a minority of the manuscripts reported the proportion of patients with lymphopenia, and variable cutoffs based on the articles' reference ranges made it difficult to ascertain a cutoff for severe disease.

With the rising cases of COVID-19 and limited resources,[14] being able to prioritize patients with severe disease is crucial. Some therapeutic agents are being investigated;[15] however, supplies are often low and procurement may be delayed. The sooner patients with severe disease can be identified, the sooner the process of obtaining therapy can be initiated.