Lymphocytopenia is a low lymphocyte count which may occur due to the body not producing enough lymphocytes, lymphocytes being destroyed in the body or lymphocytes getting trapped in the spleen or lymph nodes. Lymphocytopenia refers to a total lymphocyte count of less than 1000/mcL (less than 1 x 109/L) in adults for less than 3000/mcL (less than 3 x 109/L) in children under 2 years old. Lymphocytopenia may lead to opportunistic infections and an increased risk of malignant and autoimmune disorders. Lymphocytopenia is most commonly caused by protein-energy undernutrition, AIDS and other viral infections. Lymphocytopenia may occur with lymphomas and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis or myasthenia gravis and protein-losing enteropathy caused by gastrointestinal disease or contrictive pericarditis. Inherited lymphocytopenia occurs in severe combine immunodeficiency disorder and Wiskott-Aldrich syndrome.
In COVID-19 disease caused by coronavirus SARS-CoV-2, blood lymphocyte percentage is suggested to be an indicator of disease progression. A Time-LYM% model (TLM) was established for disease classification and prognosis prediction. Patients have varying lymphocyte percentage after the onset of COVID-19. At 10-12 days after onset of symptoms, patients with lymphocyte percentage of more than 20% are classified as moderate and may recover quickly. Patients with less than 20% lymphocytes in the blood are classified as severe. At the second time point 17-19 days after symptom onset, patients with more than 20% lymphocytes in blood are in recovery and patients with between 5% and 20% lymphocytes are in danger and those with less than 5% lymphocytes become critically ill with high mortality rate.
Tan et al. (2020) suggested the following mechanisms by which SARS-CoV-2 may cause lymphocytopenia: 1) The virus may directly infect lymphocytes which express ACE2 the coronavirus receptor; 2) The virus may destroy lymphatic organs; 3) Abnormal inflammatory cytokine response may lead to lymphocyte apoptosis; 4) Severe type COVID-19 patients may have elevated metabolic molecules such as blood lactic acid that could suppress proliferation of lymphocytes.
In a meta-analysis, lymphopenia was been associated with a 3-fold higher risk of developing severe COVID-19. The authors suggested that a lymphocyte count of less than 1.5 x 109/L may be useful for predicting clinical outcomes.