Hojat Dehghanbanadaki
1,2 
, Hossein Aazami
3,4 , Mahya Shabani
5 , Dorsa Amighi
5, Farhad Seif
6 , Ali Zare Dehnavi
5 , Abdolkarim Hajighadery
7 , Mohammad-Mehdi Mehrabi Nejad
7 , Mohammad Ghafouri
5 , Nima Hajizadeh
8 , Fateme Abedin
5 , Zahra Hajizadeh
8 , Mehrdad Heravi
9 , Parsa Panahi
10 , Ali Kabir
11* 1 Metabolomics and Genomics Research Center Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2 Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
4 Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
5 Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
6 Department of Immunology and Allergy, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran
7 Department of Radiology, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
8 School of Medicine, Iran University of Medical Sciences, Tehran, Iran
9 School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
10 Student Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
11 Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Prominent prognostic parameters that reflect the severity of coronavirus disease 2019 (COVID-19) to adopt an appropriate therapeutic approach are not fully identified. This systematic review and meta-analysis aimed to explore the association between lymphocyte variation and disease severity in COVID-19 individuals.
Methods: We searched Web of Science, Scopus, PubMed, EMBASE and WHO website to retrieve studies investigating lymphocyte subset counts in non-severe and severe cases of COVID-19. The pooled standardized mean difference (SMD) between two groups and the pooled average count of each lymphocyte subset were assessed by employing a random-effect model.
Results: Thirty-nine investigations on 5087 participants, including 3578 non-severe patients and 1509 severe patients, were included. The pooled analysis showed that non-severe patients had higher total T lymphocytes (SMD = 1.01; 95% CI: 0.82, 1.20; I2 = 75.7%), T helper cells (SMD = 1.07; 95% CI: 0.85, 1.28; I2 = 85.4%), T cytotoxic cells (SMD = 1.07; 95% CI: 0.82, 1.32; I2 = 87.1%), B cells (SMD = 0.72; 95% CI: 0.45, 0.98; I2 = 79.7%), and natural killer cells (SMD = 0.65; 95% CI: 0.47, 0.84; I2 = 63.1%) than severe patients and the average count of the corresponding lymphocyte signatures in non-severe patients/severe patients were 878.88/448.40, 493.12/268.96, 311.91/158.91, 177.09/110.37, and 155.02/103.09 cells/μL, respectively.
Conclusion: Lymphopenia may be a dilemma in COVID-19 management because over-activation of lymphocytes may lead to cytokine storm or acute respiratory distress syndrome (ARDS). In contrast, lymphopenia may increase SARS-CoV-2 amplification and COVID-19 severity. Therefore, novel therapies targeting lymphocyte proliferation or contraction may counterbalance lymphocyte counts in these patients.