Lymphocytes play a decisive role in maintaining immune homeostasis and inflammatory response throughout the body. Understanding the mechanism of reduced blood lymphocyte levels is expected to provide an effective strategy for the treatment of COVID-19. We speculated four potential mechanisms leading to lymphocyte deficiency. (1) The virus might directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes express the coronavirus receptor ACE2 and may be a direct target of viruses.5 (2) The virus might directly destroy lymphatic organs. Acute lymphocyte decline might be related to lymphocytic dysfunction, and the direct damage of novel coronavirus virus to organs such as thymus and spleen cannot be ruled out. This hypothesis needs to be confirmed by pathological dissection in the future. (3) Inflammatory cytokines continued to be disordered, perhaps leading to lymphocyte apoptosis. Basic researches confirmed that tumour necrosis factor (TNF)α, interleukin (IL)-6, and other pro-inflammatory cytokines could induce lymphocyte deficiency.6 (4) Inhibition of lymphocytes by metabolic molecules produced by metabolic disorders, such as hyperlactic acidemia. The severe type of COVID-19 patients had elevated blood lactic acid levels, which might suppress the proliferation of lymphocytes.7 Multiple mechanisms mentioned above or beyond might work together to cause lymphopenia, and further research is needed.

In conclusion, lymphopenia is an effective and reliable indicator of the severity and hospitalization in COVID-19 patients. We suggest that TLM should be included in the diagnosis and therapeutic guidelines of COVID-19.