A meta‐analysis of SARS‐CoV‐2 patients identifies the combinatorial significance of D‐dimer, C‐reactive protein, lymphocyte, and neutrophil values as a predictor of disease severity

Singh, Kunwar; Mittal, Sasha; Gollapudi, Sumanth; Butzmann, Alexandra; Kumar, Jyoti; Ohgami, Robert S.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), known to be the causative agent of COVID‐19, has led to a worldwide pandemic. At presentation, individual clinical laboratory blood values, such as lymphocyte counts or C‐reactive protein (CRP) levels, may be abnormal and associated with disease severity. However, combinatorial interpretation of these laboratory blood values, in the context of COVID‐19, remains a challenge. METHODS: To assess the significance of multiple laboratory blood values in patients with SARS‐CoV‐2 and develop a COVID‐19 predictive equation, we conducted a literature search using PubMed to seek articles that included defined laboratory data points along with clinical disease progression. We identified 9846 papers, selecting primary studies with at least 20 patients for univariate analysis to identify clinical variables predicting nonsevere and severe COVID‐19 cases. Multiple regression analysis was performed on a training set of patient studies to generate severity predictor equations, and subsequently tested on a validation cohort of 151 patients who had a median duration of observation of 14 days. RESULTS: Two COVID‐19 predictive equations were generated: one using four variables (CRP, D‐dimer levels, lymphocyte count, and neutrophil count), and another using three variables (CRP, lymphocyte count, and neutrophil count). In adult and pediatric populations, the predictive equations exhibited high specificity, sensitivity, positive predictive values, and negative predictive values. CONCLUSION: Using the generated equations, the outcomes of COVID‐19 patients can be predicted using commonly obtained clinical laboratory data. These predictive equations may inform future studies evaluating the long‐term follow‐up of COVID‐19 patients.