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Mild and Asymptomatic COVID-19 Convalescents Present Long-Term Endotype of Immunosuppression Associated With Neutrophil Subsets Possessing Regulatory Functions.
Sieminska, Izabela; Weglarczyk, Kazimierz; Surmiak, Marcin; Kurowska-Baran, Dorota; Sanak, Marek; Siedlar, Maciej; Baran, Jarek.
  • Sieminska I; Department of Clinical Immunology, Jagiellonian University Medical College, Krakow, Poland.
  • Weglarczyk K; Department of Clinical Immunology, Jagiellonian University Medical College, Krakow, Poland.
  • Surmiak M; Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
  • Kurowska-Baran D; Department of Clinical Microbiology, Laboratory of Virology and Serology, University Children's Hospital, Krakow, Poland.
  • Sanak M; Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
  • Siedlar M; Department of Clinical Immunology, Jagiellonian University Medical College, Krakow, Poland.
  • Baran J; Department of Clinical Immunology, Jagiellonian University Medical College, Krakow, Poland.
Front Immunol ; 12: 748097, 2021.
Article in English | MEDLINE | ID: covidwho-1477829
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+ 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Myeloid-Derived Suppressor Cells / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Prognostic study Topics: Long Covid Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.748097

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Myeloid-Derived Suppressor Cells / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Prognostic study Topics: Long Covid Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.748097