Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.

Circulating myeloid-derived suppressor cells may be a useful biomarker in the follow-up of unvaccinated COVID-19 patients after hospitalization

“…Furthermore, blood M-MDSCs showed a negative correlation with activated T cells ( 12 ). In a recent study, we also found that peripheral blood G-MDSCs could serve as a marker for mortality in ICU-admitted patients with COVID-19 ( 13 ). Other studies have also suggested that MDSCs might influence both disease severity and mortality ( 14 , 15 ).…”

Advances in the study of myeloid-derived suppressor cells in infectious lung diseases

“…Significantly, a link between MDSCs and COVID-19 has been identified in a number of recent investigations ( Table 1 ). Compared with healthy subjects or patients with mild COVID-19, the frequency of PMN-MDSCs in the peripheral blood of COVID-19 increases with disease exacerbation, especially in severe instances and deceased patients, and proliferating PMN-MDSCs will further suppress T cells, resulting in a reduction in lymphocytes and further compromising the host immune response, so establishing a vicious cycle ( 7 , 20 , 44 , 45 ). Comparison with indicators reflecting disease severity (levels of C-reactive protein, ferritin, and lactate dehydrogenase) demonstrated that these indicators were elevated with PMN-MDSCs in severe cases, especially immature PMN-MDSCs, confirming a positive correlation between PMN-MDSCs and COVID-19 severity ( 41 ).…”

“…In contrast to these results, Japanese researchers found that the frequency of PMN-MDSCs (but not other MDSC subgroups) may be transiently elevated in patients surviving severe COVID-19 compared to patients dying from severe COVID-19, and the investigators suggest that PMN-MDSCs may reduce detrimental immune responses and be associated with genetic factors ( 36 ). In severely sick individuals, low levels of PMN-MDSCs may aid in survival ( 45 ). However, the majority of investigations have revealed that the frequency of M-MDSCs in peripheral blood following COVID-19 therapy is substantially linked with disease severity ( 8 , 37 ).…”

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

“…The results of the follow-up demonstrated steadily elevated counts of MDSCs until death in the peripheral blood of patients who eventually died. Discharged patients experienced a transitory increase in the counts of MDSCs during the first two weeks after ICU admission with a subsequent decline to baseline levels at discharge [ 103 ]. Similarly, Trombetta et a .…”