tetano
Editor, Senior Moderator
Front Immunol
. 2021 Sep 29;12:748097.
doi: 10.3389/fimmu.2021.748097. eCollection 2021.
Mild and Asymptomatic COVID-19 Convalescents Present Long-Term Endotype of Immunosuppression Associated With Neutrophil Subsets Possessing Regulatory Functions
Izabela Siemińska[SUP] 1 [/SUP], Kazimierz Węglarczyk[SUP] 1 [/SUP], Marcin Surmiak[SUP] 2 [/SUP], Dorota Kurowska-Baran[SUP] 3 [/SUP], Marek Sanak[SUP] 2 [/SUP], Maciej Siedlar[SUP] 1 [/SUP], Jarek Baran[SUP] 1 [/SUP]
Affiliations
Abstract
The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8[SUP]+[/SUP] and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.
Keywords: COVID-19 convalescents; granulocyte-macrophage colony stimulating factor (GM-CSF); granulocytic myeloid-derived suppressor cells (PMN-MDSCs); immunosuppression; low-density neutrophils (LDNs); normal density neutrophils.
. 2021 Sep 29;12:748097.
doi: 10.3389/fimmu.2021.748097. eCollection 2021.
Mild and Asymptomatic COVID-19 Convalescents Present Long-Term Endotype of Immunosuppression Associated With Neutrophil Subsets Possessing Regulatory Functions
Izabela Siemińska[SUP] 1 [/SUP], Kazimierz Węglarczyk[SUP] 1 [/SUP], Marcin Surmiak[SUP] 2 [/SUP], Dorota Kurowska-Baran[SUP] 3 [/SUP], Marek Sanak[SUP] 2 [/SUP], Maciej Siedlar[SUP] 1 [/SUP], Jarek Baran[SUP] 1 [/SUP]
Affiliations
- PMID: 34659245
- PMCID: PMC8511487
- DOI: 10.3389/fimmu.2021.748097
Abstract
The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8[SUP]+[/SUP] and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.
Keywords: COVID-19 convalescents; granulocyte-macrophage colony stimulating factor (GM-CSF); granulocytic myeloid-derived suppressor cells (PMN-MDSCs); immunosuppression; low-density neutrophils (LDNs); normal density neutrophils.