The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes

Abstract

ObjectivesThe longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.MethodsParameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.ResultsThis study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR−CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers.ConclusionsThis study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.

“The Good, the Bad and the Ugly”: Interplay of Innate Immunity and Inflammation

“…However, it would be the early immunological features which define the prognosis of the disease in these patients. Notably, proinflammatory monocytes were found to be elevated in the circulation at early stages of the disease in deceased patients [75] together with delayed antibody response which correlated with poor clinical outcome of the disease [82]. This late onset in the humoral response is in line with the delay in differentiation of plasma cells in severe [83].…”

“…Interestingly, although not all COVID-19 patients develop severe respiratory illness [73], some cases would progress to a cytokine storm, acute respiratory distress syn-drome (ARDS), and multiorgan dysfunction [74]. As a matter of act in fatal cases, inflammatory increased cytokines [75] together with mononuclear infiltrate in the lungs have been observed throughout the time [76]. Moreover, inflammatory CD14+/CD16+ monocytes, which are related to chronic inflammation and autoimmunity [77][78][79], have been found to be expanded in the peripheral blood of those patients who require hospitalization [80,81] reinforcing the idea that innate immune cells determine the outcome of cytokine dysregulation.…”

Myeloid-derived suppressor cells in COVID-19: A review

“… No change in e-MDSC (proportion) No [ 2 ] 14 N = 58 (COVID-19: 13 moderate, 37 severe; HD: 8) PB No Fresh M-MDSC: HLA-DR -/dim CD11b + CD14 + CD15 − PMN-MDSC: HLA-DR -/dim CD11b + CD14 − CD15 + Increase in M-MDSC and PMN-MDSC (proportion, in patients as compared to HD) No [ 84 ] 15 N = 26 (COVID-19: 13 convalescent; HD: 13) PB Yes Fresh M-MDSC: Lin − HLA-DR -/dim CD11b + CD14 + CD15 − PMN-MDSC: Lin − HLA-DR -/dim CD11b + CD14 − CD15 + e-MDSC: Lin − HLA-DR − CD11b + CD14 − CD15 − Increase in PMN-MDSC (proportion, in convalescent patients as compared to HD). No change in M-MDSC and e-MDSC (proportion) Inhibition of antigen-nonspecific T cell proliferation [ 68 ] 16 N = 67 (COVID-19: 26 mild, 15 severe; HD: 26) PB Yes Fresh M-MDSC: HLA-DR − CD11b + CD66b − CD14 + CD15 − PMN-MDSC: HLA-DR − CD11b + CD66b + CD14 − CD15 + Increase in M-MDSC and PMN-MDSC (proportion, in patients as compared to HD; increase in PMN-MDSC in mild patients as compared to severe patients) No [ 70 ] 17 N = 120 (COVID-19: 27 mild, 47 severe, 46 deceased) PB No Fresh M-MDSC: HLA-DR − CD14 + Increase in M-MDSC (proportion, in deceased patients as compared to mild and severe patients) No [ 3 ] 18 N = 80 (COVID-19: 40 ICU discharged, 40 ICU deceased) PB No Fresh <...>…”

“…Falck-Jones et al demonstrated that an early increase in M-MDSC frequency was associated with later disease severity [ 63 ]. A study by Tang et al , which enrolled 27 mild, 47 severe and 46 deceased COVID-19 patients, demonstrated that an M-MDSC cutoff value of ≥10%, as estimated in the CD14 + gate, predicted COVID-19 mortality [ 3 ]. On the other hand, a study by Mortaz et al of 37 severe and 13 moderate COVID-19 patients showed that neither the frequency of M-MDSC nor PMN-MDSCs in peripheral blood predicted either the survival of patients or severity of infection [ 84 ].…”

“…Massive expansion of the myeloid cell compartment and a decrease in the leukocyte compartment have been repeatedly observed in patients with severe COVID-19, emphasizing an important role of myeloid cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [ [1] , [2] , [3] ]. Myeloid cells in COVID-19 are characterized by diminished antigen-presenting and increased immunosuppressive characteristics, both of which are consistent with the MDSC profile [ 4 , 5 ].…”