Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis

Abstract Objective Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Methods Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. Results There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). Conclusion This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.