Abstract

The lymphopenia as a major immunological abnormality occurs in the majority of severe COVID-19 patients, which is strongly associated with mortality rate. A low proportion of lymphocytes may express the main receptor for SARS-CoV-2, called angiotensin-converting enzyme 2 (ACE2). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also use ACE2-independent pathways to enter lymphocytes. Both SARS-CoV-2- and immune-mediated mechanisms may contribute to the occurrence of lymphopenia through influencing the lymphocyte production, survival or tissue re-distribution. The metabolic and biochemical changes can also affect the production and survival of lymphocytes in COVID-19 patients. Lymphopenia can cause general immunosuppression and promote cytokine storm, both of them play an important role in the viral persistence, viral replication, multi-organ failure and eventually death. Here, a comprehensive view concerning the possible mechanisms that may lead to the lymphocyte reduction in COVID-19 patients is provided, while highlighting the potential intervention approaches to prevent lymphopenia.