Activated CD8+CD38+ Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients

被引:12
作者
Bobcakova, Anna [1 ]
Barnova, Martina [2 ]
Vysehradsky, Robert [1 ]
Petriskova, Jela [2 ]
Kocan, Ivan [1 ]
Diamant, Zuzana [3 ,4 ,5 ,6 ]
Jesenak, Milos [1 ,2 ,7 ]
机构
[1] Comenius Univ, Martin Univ Hosp, Jessenius Fac Med, Ctr Primary Immunodeficiencies,Clin Pneumol & Pht, Martin, Slovakia
[2] Martin Univ Hosp, Dept Clin Immunol & Allergol, Martin, Slovakia
[3] Lund Univ, Inst Clin Sci, Dept Resp Med & Allergol, Skane Univ Hosp, Lund, Sweden
[4] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, KU Leuven, Leuven, Belgium
[5] Charles Univ Prague, Fac Med 1, Dept Resp Med, Prague, Czech Republic
[6] Thomayer Hosp, Prague, Czech Republic
[7] Comenius Univ, Martin Univ Hosp, Jessenius Fac Med, Ctr Primary Immunodeficiencies,Clin Pediat, Martin, Slovakia
关键词
SARS-CoV-2; COVID-19; immune cell dysregulation; activated CD8(+) cells; clinical outcome; immunologic predictors; CORONAVIRUS DISEASE 2019; CD8(+) T-CELLS; SARS-COV-2; WUHAN; NKG2A;
D O I
10.3389/fimmu.2022.861666
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3(+), CD4(+), CD8(+), CD19(+), NK cells, CD4(+)CD45RO(+)), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8(+)CD38(+) cells and significantly lower proportion of CD8(+)NKG2A(+) and NK NKG2A(+) cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8(+)CD38(+)cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.
引用
收藏
页数:15
相关论文
共 78 条
[1]   NKG2A and COVID-19: another brick in the wall [J].
Antonioli, Luca ;
Fornai, Matteo ;
Pellegrini, Carolina ;
Blandizzi, Corrado .
CELLULAR & MOLECULAR IMMUNOLOGY, 2020, 17 (06) :672-674
[2]   The Ability to Normalise Energy Metabolism in Advanced COVID-19 Disease Seems to Be One of the Key Factors Determining the Disease Progression-A Metabolomic NMR Study on Blood Plasma [J].
Baranovicova, Eva ;
Bobcakova, Anna ;
Vysehradsky, Robert ;
Dankova, Zuzana ;
Halasova, Erika ;
Nosal, Vladimir ;
Lehotsky, Jan .
APPLIED SCIENCES-BASEL, 2021, 11 (09)
[3]   Inhibitory Immune Checkpoint Molecules and Exhaustion of T cells in COVID-19 [J].
Barnova, Martina ;
Bobcakova, Anna ;
Urdova, Veronika ;
Kosturiak, Radovan ;
Kapustova, Lenka ;
Dobrota, Dusan ;
Jesenak, Milos .
PHYSIOLOGICAL RESEARCH, 2021, 70 :S227-S247
[4]   Complement cascade in severe forms of COVID-19: Recent advances in therapy [J].
Benmansour, Nassima Chouaki ;
Carvelli, Julien ;
Vivier, Eric .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2021, 51 (07) :1652-1659
[5]   Remdesivir significantly reduces SARS-CoV-2 viral load on nasopharyngeal swabs in hospitalized patients with COVID-19: A retrospective case-control study [J].
Biancofiore, Annalucia ;
Mirijello, Antonio ;
Puteo, Maria A. ;
Di Viesti, Maria P. ;
Labonia, Maria ;
Copetti, Massimiliano ;
De Cosmo, Salvatore ;
Lombardi, Renato .
JOURNAL OF MEDICAL VIROLOGY, 2022, 94 (05) :2284-2289
[6]   Immune Profile in Patients With COVID-19: Lymphocytes Exhaustion Markers in Relationship to Clinical Outcome [J].
Bobcakova, Anna ;
Petriskova, Jela ;
Vysehradsky, Robert ;
Kocan, Ivan ;
Kapustova, Lenka ;
Barnova, Martina ;
Diamant, Zuzana ;
Jesenak, Milos .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2021, 11
[7]   HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C [J].
Braud, VM ;
Allan, DSJ ;
O'Callaghan, CA ;
Söderström, K ;
D'Andrea, A ;
Ogg, GS ;
Lazetic, S ;
Young, NT ;
Bell, JI ;
Phillips, JH ;
Lanier, LL ;
McMichael, AJ .
NATURE, 1998, 391 (6669) :795-799
[8]   Baricitinib restrains the immune dysregulation in patients with severe COVID-19 [J].
Bronte, Vincenzo ;
Ugel, Stefano ;
Tinazzi, Elisa ;
Vella, Antonio ;
De Sanctis, Francesco ;
Cane, Stefania ;
Batani, Veronica ;
Trovato, Rosalinda ;
Fiore, Alessandra ;
Petrova, Varvara ;
Hofer, Francesca ;
Barouni, Roza Maria ;
Musiu, Chiara ;
Caligola, Simone ;
Pinton, Laura ;
Torroni, Lorena ;
Polati, Enrico ;
Donadello, Katia ;
Friso, Simonetta ;
Pizzolo, Francesca ;
Iezzi, Manuela ;
Facciotti, Federica ;
Pelicci, Pier Giuseppe ;
Righetti, Daniela ;
Bazzoni, Paolo ;
Rampudda, Mariaelisa ;
Comel, Andrea ;
Mosaner, Walter ;
Lunardi, Claudio ;
Olivieri, Oliviero .
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (12) :6409-6416
[9]   Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India [J].
Chandele, Anmol ;
Sewatanon, Jaturong ;
Gunisetty, Sivaram ;
Singla, Mohit ;
Onlamoon, Nattawat ;
Akondy, Rama S. ;
Kissick, Haydn Thomas ;
Nayak, Kaustuv ;
Reddy, Elluri Seetharami ;
Kalam, Haroon ;
Kumar, Dhiraj ;
Verma, Anil ;
Panda, HareKrushna ;
Wang, Siyu ;
Angkasekwinai, Nasikarn ;
Pattanapanyasat, Kovit ;
Chokephaibulkit, Kulkanya ;
Medigeshi, Guruprasad R. ;
Lodha, Rakesh ;
Kabra, Sushil ;
Ahmed, Rafi ;
Murali-Krishna, Kaja .
JOURNAL OF VIROLOGY, 2016, 90 (24) :11259-11278
[10]   Effects of dexamethasone on immune dysfunction and ventilator-associated pneumonia in COVID-19 acute respiratory distress syndrome: an observational study [J].
Cour, Martin ;
Simon, Marie ;
Argaud, Laurent ;
Monneret, Guillaume ;
Venet, Fabienne .
JOURNAL OF INTENSIVE CARE, 2021, 9 (01)