PMC:7736111 / 116189-118360 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7736111","sourcedb":"PMC","sourceid":"7736111","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7736111","text":"In addition to the mechanism mentioned above associated with lymphocytopenia, secondary signaling mediated via engagement of death receptors, increased ROS, HMGB1 and other death-inducing agents released by the infected and damaged ATII cells may also be implicated in T cell decline (Kaminskyy and Zhivotovsky, 2010; Juno et al., 2017; Zhan et al., 2017). Thus, based on these early findings, lymphocyte exhaustion may be driven by multiple factors that actively engage in rendering these cells ineffective, followed by their subsequent elimination (lymphocytopenia). Overall, a clear picture is emerging, which strongly indicates lymphocytopenia as a predictive marker for COVID-19 disease severity. Along with increased neutrophil number, the blood lymphocyte count serves as a better prognostic marker and reflects the immunopathological state of the patients (Giamarellos-Bourboulis et al., 2020; Liu et al., 2020b). Further, based on these emerging studies, it is becoming evident that T cell response is heterogeneous during COVID-19 infection. While peripheral blood may exhibit lymphocytopenia, and mostly exhausted status of these cells, the site of infection is associated with an activated profile of the cells and hence determines the severity of the disease. Thus, caution should be exercised while designing therapeutic interventions for COVID-19. The underlying immunological state should be borne in mind while considering the treatment. Patients with lymphocytopenia and elevated functional and activation status of T cells may benefit from immunomodulatory approaches like mesenchymal stem cells, which are currently under clinical trials (NCT04377334). Patients with imperfect T cell and B cell responses may benefit from convalescent plasma therapy, whereas patients with impaired interferon response may respond better to interferon therapies (NCT04350671; NCT04388709). Thus, before a vaccine is available, a rational way to recommend therapy for severe cases of COVID-19 should be based on the patient’s underlying immunological state. However, the treatment options become challenging when the patients exhibit cytokine storm and associated 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