The clinical and immunological characteristics of COVID-19 patients with delayed SARS-CoV-2 virus clearance

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a great threat to human health. Some severe COVID-19 patients still carried detectable levels of SARS-CoV-2 even after prolonged intensive care unit treatment. However, the immunological features of these COVID-19 patients with delayed virus clearance (CDVC) are still unclear.MethodsWe retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (n = 9) and recovered (n = 52) cases. The expression of the exhaustion marker PD-1 on circulating T cells of these patients was measured by flow cytometry.ResultsHigh levels of serum interleukin-6 (IL-6), IL-1 & beta;, IL-8, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9 x 109/L), CD4+ T cells (0.35 x 109/L), and CD8+ T cells (0.28 x 109/L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25+Foxp3+ regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD-1 on CCR7-CD45RA+ effector, CCR7+CD45RA- central memory, and CCR7-CD45RA- effector memory CD4+ and CD8+ T cells were also observed in CDVC cases.ConclusionCDVC patients still have SARS-CoV-2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS-CoV-2. Therefore, enhancing lymphocyte counts and reversing T-cell exhaustion might be key methods to boost immune responses and eliminate SARS-CoV-2 in CDVC patients. CDVC patients still have SARS-CoV-2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS-CoV-2. Therefore, enhancing lymphocyte counts and reversing T-cell exhaustion might be key methods to boost immune responses and eliminate SARS-CoV-2 in CDVC patients.image