Skip to main content
Top
Published in: Annals of Intensive Care 1/2021

Open Access 01-12-2021 | Septicemia | Research

Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

Authors: Clémence Marais, Caroline Claude, Nada Semaan, Ramy Charbel, Simon Barreault, Brendan Travert, Jean-Eudes Piloquet, Zoé Demailly, Luc Morin, Zied Merchaoui, Jean-Louis Teboul, Philippe Durand, Jordi Miatello, Pierre Tissières, for The COVID-19 Immune Suppression (CLOVIS) Study Group

Published in: Annals of Intensive Care | Issue 1/2021

Login to get access

Abstract

Background

De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit.

Methods

Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression.

Results

Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression.

Conclusions

Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.
Appendix
Available only for authorised users
Literature
2.
go back to reference Giacobbe DR, Battaglini D, Ball L, Brunetti I, Bruzzone B, Codda G, Crea F, De Maria A, Dentone C, Di Biagio A, Icardi G, Magnasco L, Marchese A, Mikulska M, Orsi A, Patroniti N, Robba C, Signori A, Taramasso L, Vena A, Pelosi P, Bassetti M. Bloodstream infections in critically ill patients with COVID-19. Eur J Clin Investig. 2020. https://doi.org/10.1111/eci.13319.CrossRef Giacobbe DR, Battaglini D, Ball L, Brunetti I, Bruzzone B, Codda G, Crea F, De Maria A, Dentone C, Di Biagio A, Icardi G, Magnasco L, Marchese A, Mikulska M, Orsi A, Patroniti N, Robba C, Signori A, Taramasso L, Vena A, Pelosi P, Bassetti M. Bloodstream infections in critically ill patients with COVID-19. Eur J Clin Investig. 2020. https://​doi.​org/​10.​1111/​eci.​13319.CrossRef
9.
go back to reference Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, Almire C, Hénon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel TA, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur AS, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng LG, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pène F, Gachot B, André F, Zitvogel L, Ginhoux F, Fontenay M, Solary E. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020;182(6):1401-1418.e18. https://doi.org/10.1016/j.cell.2020.08.002 (Epub 2020 Aug 5).CrossRefPubMedPubMedCentral Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, Almire C, Hénon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel TA, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur AS, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng LG, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pène F, Gachot B, André F, Zitvogel L, Ginhoux F, Fontenay M, Solary E. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020;182(6):1401-1418.e18. https://​doi.​org/​10.​1016/​j.​cell.​2020.​08.​002 (Epub 2020 Aug 5).CrossRefPubMedPubMedCentral
10.
go back to reference Remy KE, Mazer M, Striker DA, Ellebedy AH, Walton AH, Unsinger J, Blood TM, Mudd PA, Yi DJ, Mannion DA, Osborne DF, Martin RS, Anand NJ, Bosanquet JP, Blood J, Drewry AM, Caldwell CC, Turnbull IR, Brakenridge SC, Moldwawer LL, Hotchkiss RS. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020;5(17):e140329. https://doi.org/10.1172/jci.insight.140329.CrossRefPubMedCentral Remy KE, Mazer M, Striker DA, Ellebedy AH, Walton AH, Unsinger J, Blood TM, Mudd PA, Yi DJ, Mannion DA, Osborne DF, Martin RS, Anand NJ, Bosanquet JP, Blood J, Drewry AM, Caldwell CC, Turnbull IR, Brakenridge SC, Moldwawer LL, Hotchkiss RS. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020;5(17):e140329. https://​doi.​org/​10.​1172/​jci.​insight.​140329.CrossRefPubMedCentral
13.
go back to reference O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad II, Randolph AG, Rupp ME, Saint S, Healthcare Infection Control Practices Advisory Committee. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4 Suppl 1):S1-34. https://doi.org/10.1016/j.ajic.2011.01.003.CrossRefPubMed O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad II, Randolph AG, Rupp ME, Saint S, Healthcare Infection Control Practices Advisory Committee. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4 Suppl 1):S1-34. https://​doi.​org/​10.​1016/​j.​ajic.​2011.​01.​003.CrossRefPubMed
14.
go back to reference Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5): e61–e111. https://doi.org/10.1093/cid/ciw353. (Epub 2016 Jul 14). Erratum in: Clin Infect Dis. 2017;64(9):1298. Erratum in: Clin Infect Dis. 2017;65(8):1435. Erratum in: Clin Infect Dis. 2017;65(12):2161. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5): e61–e111. https://​doi.​org/​10.​1093/​cid/​ciw353. (Epub 2016 Jul 14). Erratum in: Clin Infect Dis. 2017;64(9):1298. Erratum in: Clin Infect Dis. 2017;65(8):1435. Erratum in: Clin Infect Dis. 2017;65(12):2161.
20.
go back to reference Carter MJ, Fish M, Jennings A, Doores KJ, Wellman P, Seow J, Acors S, Graham C, Timms E, Kenny J, Neil S, Malim MH, Tibby SM, Shankar-Hari M. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020;26(11):1701–7. https://doi.org/10.1038/s41591-020-1054-6 (Epub 2020 Aug 18).CrossRefPubMed Carter MJ, Fish M, Jennings A, Doores KJ, Wellman P, Seow J, Acors S, Graham C, Timms E, Kenny J, Neil S, Malim MH, Tibby SM, Shankar-Hari M. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020;26(11):1701–7. https://​doi.​org/​10.​1038/​s41591-020-1054-6 (Epub 2020 Aug 18).CrossRefPubMed
24.
go back to reference Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992-1000.e3. https://doi.org/10.1016/j.chom.2020.04.009 (Epub 2020 Apr 21).CrossRefPubMedPubMedCentral Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992-1000.e3. https://​doi.​org/​10.​1016/​j.​chom.​2020.​04.​009 (Epub 2020 Apr 21).CrossRefPubMedPubMedCentral
25.
27.
go back to reference Arunachalam PS, Wimmers F, Mok CKP, Perera RAPM, Scott M, Hagan T, Sigal N, Feng Y, Bristow L, Tak-Yin Tsang O, Wagh D, Coller J, Pellegrini KL, Kazmin D, Alaaeddine G, Leung WS, Chan JMC, Chik TSH, Choi CYC, Huerta C, Paine McCullough M, Lv H, Anderson E, Edupuganti S, Upadhyay AA, Bosinger SE, Maecker HT, Khatri P, Rouphael N, Peiris M, Pulendran B. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020;369(6508):1210–20. https://doi.org/10.1126/science.abc6261 (Epub 2020 Aug 11).CrossRefPubMedPubMedCentral Arunachalam PS, Wimmers F, Mok CKP, Perera RAPM, Scott M, Hagan T, Sigal N, Feng Y, Bristow L, Tak-Yin Tsang O, Wagh D, Coller J, Pellegrini KL, Kazmin D, Alaaeddine G, Leung WS, Chan JMC, Chik TSH, Choi CYC, Huerta C, Paine McCullough M, Lv H, Anderson E, Edupuganti S, Upadhyay AA, Bosinger SE, Maecker HT, Khatri P, Rouphael N, Peiris M, Pulendran B. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020;369(6508):1210–20. https://​doi.​org/​10.​1126/​science.​abc6261 (Epub 2020 Aug 11).CrossRefPubMedPubMedCentral
28.
go back to reference Reyes M, Filbin MR, Bhattacharyya RP, Sonny A, Mehta A, Billman K, Kays KR, Pinilla-Vera M, Benson ME, Cosimi LA, Hung DT, Levy BD, Villani AC, Sade-Feldman M, Baron RM, Goldberg MB, Blainey PC, Hacohen N. Induction of a regulatory myeloid program in bacterial sepsis and severe COVID-19. bioRxiv. 2020:2020.09.02.280180. https://doi.org/10.1101/2020.09.02.280180. (Preprint). Reyes M, Filbin MR, Bhattacharyya RP, Sonny A, Mehta A, Billman K, Kays KR, Pinilla-Vera M, Benson ME, Cosimi LA, Hung DT, Levy BD, Villani AC, Sade-Feldman M, Baron RM, Goldberg MB, Blainey PC, Hacohen N. Induction of a regulatory myeloid program in bacterial sepsis and severe COVID-19. bioRxiv. 2020:2020.09.02.280180. https://​doi.​org/​10.​1101/​2020.​09.​02.​280180. (Preprint).
29.
go back to reference Thompson E, Cascino K, Ordonez A, Zhou W, Vaghasia A, Hamacher-Brady A, Brady N, Sun IH, Wang R, Rosenberg A, Delanoy M, Rothman RE, Fenstermacher K, Sauer L, Shaw-Saliba K, Bloch EM, Redd A, Tobian AA, Horton M, Smith K, Pekosz A, D'Alessio F, Yegnasubramanian S, Ji H, Cox AL, Powell JD. Mitochondrial induced T cell apoptosis and aberrant myeloid metabolic programs define distinct immune cell subsets during acute and recovered SARS-CoV-2 infection. medRxiv. 2020:2020.09.10.20186064. https://doi.org/10.1101/2020.09.10.20186064. (Preprint). Thompson E, Cascino K, Ordonez A, Zhou W, Vaghasia A, Hamacher-Brady A, Brady N, Sun IH, Wang R, Rosenberg A, Delanoy M, Rothman RE, Fenstermacher K, Sauer L, Shaw-Saliba K, Bloch EM, Redd A, Tobian AA, Horton M, Smith K, Pekosz A, D'Alessio F, Yegnasubramanian S, Ji H, Cox AL, Powell JD. Mitochondrial induced T cell apoptosis and aberrant myeloid metabolic programs define distinct immune cell subsets during acute and recovered SARS-CoV-2 infection. medRxiv. 2020:2020.09.10.20186064. https://​doi.​org/​10.​1101/​2020.​09.​10.​20186064. (Preprint).
30.
go back to reference Sacchi A, Grassi G, Bordoni V, Lorenzini P, Cimini E, Casetti R, Tartaglia E, Marchioni L, Petrosillo N, Palmieri F, D’Offizi G, Notari S, Tempestilli M, Capobianchi MR, Nicastri E, Maeurer M, Zumla A, Locatelli F, Antinori A, Ippolito G, Agrati C. Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome. Cell Death Dis. 2020;11(10):921. https://doi.org/10.1038/s41419-020-03125-1.CrossRefPubMedPubMedCentral Sacchi A, Grassi G, Bordoni V, Lorenzini P, Cimini E, Casetti R, Tartaglia E, Marchioni L, Petrosillo N, Palmieri F, D’Offizi G, Notari S, Tempestilli M, Capobianchi MR, Nicastri E, Maeurer M, Zumla A, Locatelli F, Antinori A, Ippolito G, Agrati C. Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome. Cell Death Dis. 2020;11(10):921. https://​doi.​org/​10.​1038/​s41419-020-03125-1.CrossRefPubMedPubMedCentral
31.
go back to reference Bordoni V, Sacchi A, Cimini E, Notari S, Grassi G, Tartaglia E, Casetti R, Giancola L, Bevilacqua N, Maeurer M, Zumla A, Locatelli F, De Benedetti F, Palmieri F, Marchioni L, Capobianchi MR, D’Offizi G, Petrosillo N, Antinori A, Nicastri E, Ippolito G, Agrati C. An inflammatory profile correlates with decreased frequency of cytotoxic cells in COVID-19. Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa577 (Epub ahead of print).CrossRefPubMedPubMedCentral Bordoni V, Sacchi A, Cimini E, Notari S, Grassi G, Tartaglia E, Casetti R, Giancola L, Bevilacqua N, Maeurer M, Zumla A, Locatelli F, De Benedetti F, Palmieri F, Marchioni L, Capobianchi MR, D’Offizi G, Petrosillo N, Antinori A, Nicastri E, Ippolito G, Agrati C. An inflammatory profile correlates with decreased frequency of cytotoxic cells in COVID-19. Clin Infect Dis. 2020. https://​doi.​org/​10.​1093/​cid/​ciaa577 (Epub ahead of print).CrossRefPubMedPubMedCentral
36.
go back to reference Uhel F, Azzaoui I, Grégoire M, Pangault C, Dulong J, Tadié JM, Gacouin A, Camus C, Cynober L, Fest T, Le Tulzo Y, Roussel M, Tarte K. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(3):315–27. https://doi.org/10.1164/rccm.201606-1143OC.CrossRefPubMed Uhel F, Azzaoui I, Grégoire M, Pangault C, Dulong J, Tadié JM, Gacouin A, Camus C, Cynober L, Fest T, Le Tulzo Y, Roussel M, Tarte K. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(3):315–27. https://​doi.​org/​10.​1164/​rccm.​201606-1143OC.CrossRefPubMed
37.
go back to reference Mathias B, Delmas AL, Ozrazgat-Baslanti T, Vanzant EL, Szpila BE, Mohr AM, Moore FA, Brakenridge SC, Brumback BA, Moldawer LL, Efron PA, the Sepsis, Critical Illness Research Center Investigators. Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg. 2017;265(4):827–34. https://doi.org/10.1097/SLA.0000000000001783.CrossRefPubMed Mathias B, Delmas AL, Ozrazgat-Baslanti T, Vanzant EL, Szpila BE, Mohr AM, Moore FA, Brakenridge SC, Brumback BA, Moldawer LL, Efron PA, the Sepsis, Critical Illness Research Center Investigators. Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg. 2017;265(4):827–34. https://​doi.​org/​10.​1097/​SLA.​0000000000001783​.CrossRefPubMed
38.
39.
go back to reference Coopersmith CM, Antonelli M, Bauer SR, Deutschman CS, Evans LE, Ferrer R, Hellman J, Jog S, Kesecioglu J, Kissoon N, Martin-Loeches I, Nunnally ME, Prescott HC, Rhodes A, Talmor D, Tissieres P, De Backer D. Surviving sepsis campaign: research priorities for COVID-19 in critical illness. Crit Care Med. 2021;49(4):598–622. https://doi.org/10.1097/CCM.0000000000004895.CrossRefPubMed Coopersmith CM, Antonelli M, Bauer SR, Deutschman CS, Evans LE, Ferrer R, Hellman J, Jog S, Kesecioglu J, Kissoon N, Martin-Loeches I, Nunnally ME, Prescott HC, Rhodes A, Talmor D, Tissieres P, De Backer D. Surviving sepsis campaign: research priorities for COVID-19 in critical illness. Crit Care Med. 2021;49(4):598–622. https://​doi.​org/​10.​1097/​CCM.​0000000000004895​.CrossRefPubMed
Metadata
Title
Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study
Authors
Clémence Marais
Caroline Claude
Nada Semaan
Ramy Charbel
Simon Barreault
Brendan Travert
Jean-Eudes Piloquet
Zoé Demailly
Luc Morin
Zied Merchaoui
Jean-Louis Teboul
Philippe Durand
Jordi Miatello
Pierre Tissières
for The COVID-19 Immune Suppression (CLOVIS) Study Group
Publication date
01-12-2021
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2021
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-021-00896-4

Other articles of this Issue 1/2021

Annals of Intensive Care 1/2021 Go to the issue