PMID- 34937933 OWN - NLM STAT- MEDLINE DCOM- 20220111 LR - 20220111 IS - 1529-2916 (Electronic) IS - 1529-2908 (Linking) VI - 23 IP - 1 DP - 2022 Jan TI - Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2-specific CD8(+) T cell responses following COVID-19. PG - 23-32 LID - 10.1038/s41590-021-01095-w [doi] AB - Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates(1-6). Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c(+) natural killer (NK) cells and CD4(+) T effector cells during acute COVID-19. The mucosal proinflammatory populations positively associated with peripheral blood human leukocyte antigen (HLA)-DR(low) monocytes, CD38(+)PD1(+)CD4(+) T effector (T(eff)) cells and plasmablasts. However, there was no general lymphopenia in nasal mucosa, unlike in peripheral blood. Moreover, nasal neutrophils negatively associated with oxygen saturation levels in blood. Following convalescence, nasal immune cells mostly normalized, except for CD127(+) granulocytes and CD38(+)CD8(+) tissue-resident memory T cells (T(RM)). SARS-CoV-2-specific CD8(+) T cells persisted at least 2 months after viral clearance in the nasal mucosa, indicating that COVID-19 has both transient and long-term effects on upper respiratory tract immune responses. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Roukens, Anna H E AU - Roukens AHE AUID- ORCID: 0000-0002-1397-0992 AD - Department of Infectious Diseases, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Pothast, Cilia R AU - Pothast CR AUID- ORCID: 0000-0002-9761-3123 AD - Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Konig, Marion AU - Konig M AUID- ORCID: 0000-0002-9892-218X AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Huisman, Wesley AU - Huisman W AUID- ORCID: 0000-0002-5699-7087 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Dalebout, Tim AU - Dalebout T AUID- ORCID: 0000-0002-5916-7548 AD - Department of Medical Microbiology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Tak, Tamar AU - Tak T AUID- ORCID: 0000-0002-5959-7927 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Azimi, Shohreh AU - Azimi S AUID- ORCID: 0000-0002-3117-5722 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Kruize, Yvonne AU - Kruize Y AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Hagedoorn, Renate S AU - Hagedoorn RS AD - Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Zlei, Mihaela AU - Zlei M AUID- ORCID: 0000-0002-6865-8883 AD - Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Staal, Frank J T AU - Staal FJT AUID- ORCID: 0000-0003-1588-8519 AD - Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. FAU - de Bie, Fenna J AU - de Bie FJ AUID- ORCID: 0000-0003-3817-8616 AD - Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. FAU - van Dongen, Jacques J M AU - van Dongen JJM AUID- ORCID: 0000-0002-3650-7087 AD - Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Arbous, Sesmu M AU - Arbous SM AD - Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands. FAU - Zhang, Jaimie L H AU - Zhang JLH AUID- ORCID: 0000-0003-3064-5486 AD - Department of Infectious Diseases, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Verheij, Maaike AU - Verheij M AUID- ORCID: 0000-0001-9686-3676 AD - Department of Infectious Diseases, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Prins, Corine AU - Prins C AD - Department of Infectious Diseases, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - van der Does, Anne M AU - van der Does AM AD - Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Hiemstra, Pieter S AU - Hiemstra PS AUID- ORCID: 0000-0002-0238-5982 AD - Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. FAU - de Vries, Jutte J C AU - de Vries JJC AD - Department of Medical Microbiology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Janse, Jacqueline J AU - Janse JJ AUID- ORCID: 0000-0003-4884-5881 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Roestenberg, Meta AU - Roestenberg M AUID- ORCID: 0000-0002-5052-2830 AD - Department of Infectious Diseases, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Myeni, Sebenzile K AU - Myeni SK AD - Department of Medical Microbiology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Kikkert, Marjolein AU - Kikkert M AUID- ORCID: 0000-0002-5779-7386 AD - Department of Medical Microbiology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Yazdanbakhsh, Maria AU - Yazdanbakhsh M AUID- ORCID: 0000-0002-7666-1441 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Heemskerk, Mirjam H M AU - Heemskerk MHM AUID- ORCID: 0000-0001-6320-9133 AD - Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Smits, Hermelijn H AU - Smits HH AUID- ORCID: 0000-0001-9279-2890 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. FAU - Jochems, Simon P AU - Jochems SP AUID- ORCID: 0000-0002-4835-1032 AD - Department of Parasitology, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. s.p.jochems@lumc.nl. CN - in collaboration with BEAT-COVID group CN - in collaboration with COVID-19 LUMC group LA - eng GR - Gisela Thier Fellowship/Leids Universitair Medisch Centrum (Leiden University Medical Center)/ GR - 114025007/ZonMw (Netherlands Organisation for Health Research and Development)/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20211222 PL - United States TA - Nat Immunol JT - Nature immunology JID - 100941354 RN - 0 (Antibodies, Viral) RN - 0 (HLA-DR Antigens) SB - IM MH - Antibodies, Viral/blood MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - COVID-19/immunology/pathology MH - Granulocytes/immunology MH - HLA-DR Antigens/metabolism MH - Humans MH - Killer Cells, Natural/immunology MH - Memory T Cells/immunology MH - Monocytes/immunology MH - Nasopharynx/cytology/*immunology/virology MH - Neutrophils/immunology MH - Nose/*cytology/immunology/virology MH - Prospective Studies MH - Respiratory Mucosa/cytology/*immunology/virology MH - SARS-CoV-2/*immunology FIR - Arbous, M S IR - Arbous MS FIR - van den Berg, B M IR - van den Berg BM FIR - de Bruin-Versteeg, S IR - de Bruin-Versteeg S FIR - Cannegieter, S IR - Cannegieter S FIR - Cante, K IR - Cante K FIR - Cobbaert, C M IR - Cobbaert CM FIR - van der Does, A M IR - van der Does AM FIR - van Dongen, J J M IR - van Dongen JJM FIR - Eikenboom, J IR - Eikenboom J FIR - Feltkamp, M C W IR - Feltkamp MCW FIR - Geluk, A IR - Geluk A FIR - Goeman, J J IR - Goeman JJ FIR - Giera, M IR - Giera M FIR - Groenland, R J IR - Groenland RJ FIR - Hankemeier, T IR - Hankemeier T FIR - Heemskerk, M H M IR - Heemskerk MHM FIR - Hiemstra, P S IR - Hiemstra PS FIR - Hokke, C H IR - Hokke CH FIR - van der Holst, R IR - van der Holst R FIR - Janse, J J IR - Janse JJ FIR - Jochems, S P IR - Jochems SP FIR - Joosten, S A IR - Joosten SA FIR - Kikkert, M IR - Kikkert M FIR - Flores, S Klaver IR - Flores SK FIR - Lamont, L IR - Lamont L FIR - Mannien, J IR - Mannien J FIR - de Mooij, B IR - de Mooij B FIR - Ottenhoff, T H M IR - Ottenhoff THM FIR - Pike-Overzet, K IR - Pike-Overzet K FIR - Pongracz, T IR - Pongracz T FIR - Del Prado, M R IR - Del Prado MR FIR - Rosinach, N Queralt IR - Rosinach NQ FIR - Roestenberg, M IR - Roestenberg M FIR - Roos, M IR - Roos M FIR - Roukens, A H E IR - Roukens AHE FIR - van der Sluijs-Gelling, Alita J IR - van der Sluijs-Gelling AJ FIR - Smits, H H IR - Smits HH FIR - Snijder, E J IR - Snijder EJ FIR - Staal, F J T IR - Staal FJT FIR - Trouw, L A IR - Trouw LA FIR - Tsonaka, R IR - Tsonaka R FIR - Verhoeven, A IR - Verhoeven A FIR - Visser, L G IR - Visser LG FIR - de Vries, J J C IR - de Vries JJC FIR - van Westerloo, D J IR - van Westerloo DJ FIR - Wigbers, J IR - Wigbers J FIR - van der Wijk, H J IR - van der Wijk HJ FIR - van Wissen, R C IR - van Wissen RC FIR - Wuhrer, M IR - Wuhrer M FIR - Yazdanbakhsh, M IR - Yazdanbakhsh M FIR - Zlei, M IR - Zlei M FIR - Oud, Josine A IR - Oud JA FIR - Baysan, Meryem IR - Baysan M FIR - Wigbers, Jeanette IR - Wigbers J FIR - van Heurn, Lieke J IR - van Heurn LJ FIR - Ter Haar, Susan B IR - Ter Haar SB FIR - Toppenberg, Alexandra G L IR - Toppenberg AGL FIR - Heerdink, Laura IR - Heerdink L FIR - van IJlzinga Veenstra, Annekee A IR - van IJlzinga Veenstra AA FIR - Eikenboom, Anna M IR - Eikenboom AM FIR - Wubbolts, Julia M IR - Wubbolts JM FIR - Uzorka, Jonathan IR - Uzorka J FIR - Lijfering, Willem IR - Lijfering W FIR - Meier, Romy IR - Meier R FIR - de Jonge, Ingeborg IR - de Jonge I FIR - de Boer, Mark G J IR - de Boer MGJ FIR - van der Bom, Anske G IR - van der Bom AG FIR - Dekkers, Olaf M IR - Dekkers OM FIR - Rosendaal, Frits IR - Rosendaal F EDAT- 2021/12/24 06:00 MHDA- 2022/01/12 06:00 CRDT- 2021/12/23 05:43 PHST- 2021/04/19 00:00 [received] PHST- 2021/11/16 00:00 [accepted] PHST- 2021/12/24 06:00 [pubmed] PHST- 2022/01/12 06:00 [medline] PHST- 2021/12/23 05:43 [entrez] AID - 10.1038/s41590-021-01095-w [pii] AID - 10.1038/s41590-021-01095-w [doi] PST - ppublish SO - Nat Immunol. 2022 Jan;23(1):23-32. doi: 10.1038/s41590-021-01095-w. Epub 2021 Dec 22.