Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis
Open accessAbstract
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; I 2 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; I 2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I 2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I 2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I 2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I 2 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.
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COVID-19 severity is associated with lymphopenia.
“COVID-19 severity is associated with lymphopenia, and many studies have shown a correlation between poor disease outcome and reduced total numbers of peripheral T cells in the blood136.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [136]
Poor COVID-19 outcome correlates with reduced total numbers of peripheral T cells in the blood.
“COVID-19 severity is associated with lymphopenia, and many studies have shown a correlation between poor disease outcome and reduced total numbers of peripheral T cells in the blood136.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [136]
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- Authors
- Huang, I., & Pranata, R.
- Affiliations
- Pelita Harapan University (ID)
- Corresponding author
- Pranata, Raymond
- Venue
- Journal of Intensive Care
- Published
- 2020-05-24
- Volume
- 8
- Issue
- 1
- Pages
- 36-36
- ISSN
- 2052-0492 (ISSN-L)
- PMC
- PMC7245646
- OpenAlex
- W3026888299
- Cited by
- 662
- References
- 41
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 68 · 2023: 117 · 2022: 147 · 2021: 198 · 2020: 96
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Intensive Care (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- lymphopenia, COVID-19 pandemic, lymphocyte count, disease severity, mortality, acute respiratory distress syndrome, intensive care unit admission, prognostic factors, comorbidities, age, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, smoking, cardiovascular comorbidity, resource allocation, SARS-CoV-2, cytokine storm
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