Can Lymphocytes Be Low in Viral Infections?
Yes, lymphocyte counts can be low in viral infections, and lymphopenia is a well-recognized hematologic finding in many viral illnesses, including COVID-19, RSV, and other respiratory viruses.
Lymphopenia as a Common Viral Infection Finding
In COVID-19 infections, lymphopenia is one of the most prominent laboratory abnormalities, with the early stage of disease characterized by decreased total leukocyte counts or normal counts with decreased lymphocyte counts 1.
Specific attention should be paid when the absolute lymphocyte value falls below 0.8 × 10⁹/L, as this threshold warrants rechecking blood routine changes after 3 days 1.
Lymphopenia occurs in the majority of severe COVID-19 patients and is strongly associated with mortality rate 2. The presence of lymphopenia (less than 1.5 × 10⁹/L) is associated with nearly threefold increased risk of severe COVID-19 3.
Mechanisms and Clinical Significance
Both viral-mediated and immune-mediated mechanisms contribute to lymphopenia through influencing lymphocyte production, survival, or tissue redistribution 2.
Lymphopenia can cause general immunosuppression and promote cytokine storm, both playing important roles in viral persistence, viral replication, multi-organ failure, and death 2.
Circulating CD4+ cells, CD8+ cells, regulatory T cells, and natural killer cells may all be reduced, with greater reductions observed in critically ill patients 4.
Lymphopenia in Immunocompromised Patients
In immunocompromised patients with RSV infection, profound lymphopenia (<100 cells/mm³) is associated with progression from upper to lower respiratory tract disease 1.
An absolute lymphocyte count of 100 cells/mm³ or less at the time of RSV upper tract infection predicts progression to lower respiratory tract disease, while progression did not occur in patients with lymphocyte counts greater than 1000 cells/mm³ 1.
In HIV-infected patients, CD4+ lymphocyte counts below 200 cells/μL indicate increased susceptibility to opportunistic infections, and these patients should be suspected of having Pneumocystis pneumonia, tuberculosis, and other opportunistic infections when presenting with unexplained cough 1.
Prognostic Value
Delta lymphocytes at 24 hours (the difference between lymphocyte values at H24 and upon admission) is a significant biochemical factor associated with mortality in COVID-19 patients, with a delta <135 cells/mm³ being one of the most significant predictors (OR: 2.23) 5.
The most accurate threshold for delta lymphocytes H24 is 75 to predict severity and 135 for mortality in SARS-CoV-2 infection 5.
Common Pitfalls
Do not assume that normal or elevated white blood cell counts exclude significant viral infection, as the total WBC may be normal while lymphocyte counts are specifically decreased 1.
Avoid relying solely on a single lymphocyte measurement—serial monitoring is essential, particularly in the first 3 days of illness, as dynamic changes provide more prognostic information than static values 1, 5.
Do not overlook lymphopenia in the context of other viral infections beyond COVID-19, as similar alterations occur in various viral infections including RSV, influenza, and other respiratory viruses 4, 6.