PMID- 34347801
OWN - NLM
STAT- MEDLINE
DCOM- 20210813
LR  - 20231107
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 8
DP  - 2021
TI  - Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 
      disease.
PG  - e0255335
LID - 10.1371/journal.pone.0255335 [doi]
LID - e0255335
AB  - The SARS-CoV-2 coronavirus has led to a pandemic with millions of people 
      affected. The present study finds that risk-factors for severe COVID-19 disease 
      courses, i.e. male sex, older age and sedentary life style are associated with 
      higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected 
      subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and 
      correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation 
      and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase 
      (COX)-2 and reducing the PG-degrading enzyme 
      15-hydroxyprostaglandin-dehydrogenase. Also living human precision cut lung 
      slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular 
      exercise in aged individuals lowers PGE2 serum levels, which leads to increased 
      Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell 
      survival, proliferation and differentiation also towards long lived memory 
      B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 
      patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 
      inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, 
      SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, 
      which may reduce the early anti-viral defense as well as the development of 
      immunity promoting severe disease courses and multiple infections. Regular 
      exercise and Taxifolin treatment may reduce these risks and prevent severe 
      disease courses.
FAU - Ricke-Hoch, Melanie
AU  - Ricke-Hoch M
AUID- ORCID: 0000-0001-5479-2275
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
FAU - Stelling, Elisabeth
AU  - Stelling E
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
FAU - Lasswitz, Lisa
AU  - Lasswitz L
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
FAU - Gunesch, Antonia P
AU  - Gunesch AP
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
AD  - German Center for Infection Research, Hanover-Braunschweig Site, Braunschweig, 
      Germany.
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hanover, Germany.
FAU - Kasten, Martina
AU  - Kasten M
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
FAU - Zapatero-Belinchon, Francisco J
AU  - Zapatero-Belinchon FJ
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
AD  - Department of Clinical Microbiology, Virology & Wallenberg Centre for Molecular 
      Medicine (WCMM), Umea University, Umea, Sweden.
FAU - Brogden, Graham
AU  - Brogden G
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
FAU - Gerold, Gisa
AU  - Gerold G
AUID- ORCID: 0000-0002-1326-5038
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
AD  - Department of Clinical Microbiology, Virology & Wallenberg Centre for Molecular 
      Medicine (WCMM), Umea University, Umea, Sweden.
AD  - Department of Biochemistry, University of Veterinary Medicine Hannover, Hanover 
      Germany.
FAU - Pietschmann, Thomas
AU  - Pietschmann T
AD  - Institute of Experimental Virology, TWINCORE, Center for Experimental and 
      Clinical Infection Research Hannover, Hanover, Germany.
AD  - German Center for Infection Research, Hanover-Braunschweig Site, Braunschweig, 
      Germany.
FAU - Montiel, Virginie
AU  - Montiel V
AD  - Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et 
      Clinique, and Cliniques Universitaires Saint-Luc, Universite catholique de 
      Louvain (UCLouvain), Brussels, Belgium.
FAU - Balligand, Jean-Luc
AU  - Balligand JL
AD  - Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et 
      Clinique, and Cliniques Universitaires Saint-Luc, Universite catholique de 
      Louvain (UCLouvain), Brussels, Belgium.
FAU - Facciotti, Federica
AU  - Facciotti F
AD  - Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, 
      Italy.
FAU - Hirsch, Emilio
AU  - Hirsch E
AD  - Department of Molecular Biotechnology and Health Sciences, Molecular 
      Biotechnology Center, University of Torino, Torino, Italy.
FAU - Gausepohl, Thomas
AU  - Gausepohl T
AUID- ORCID: 0000-0003-1669-5911
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
FAU - Elbahesh, Husni
AU  - Elbahesh H
AUID- ORCID: 0000-0003-1243-0967
AD  - Research Center for Emerging Infections and Zoonoses (RIZ), University of 
      Veterinary Medicine in Hannover (TiHo), Hannover, Germany.
FAU - Rimmelzwaan, Guus F
AU  - Rimmelzwaan GF
AD  - Research Center for Emerging Infections and Zoonoses (RIZ), University of 
      Veterinary Medicine in Hannover (TiHo), Hannover, Germany.
FAU - Hofer, Anne
AU  - Hofer A
AD  - Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German 
      Center for Lung Research, Hanover, Germany.
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany.
FAU - Kuhnel, Mark P
AU  - Kuhnel MP
AD  - Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German 
      Center for Lung Research, Hanover, Germany.
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany.
FAU - Jonigk, Danny
AU  - Jonigk D
AD  - Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German 
      Center for Lung Research, Hanover, Germany.
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany.
FAU - Eigendorf, Julian
AU  - Eigendorf J
AD  - Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
FAU - Tegtbur, Uwe
AU  - Tegtbur U
AD  - Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
FAU - Mink, Lena
AU  - Mink L
AD  - Institute of Sports Medicine, Hannover Medical School, Hanover, Germany.
FAU - Scherr, Michaela
AU  - Scherr M
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hanover, Germany.
FAU - Illig, Thomas
AU  - Illig T
AD  - Hannover Unified Biobank (HUB), Hannover Medical School, Hanover, Germany.
FAU - Schambach, Axel
AU  - Schambach A
AD  - Institute of Experimental Hematology, Hannover Medical School, Hanover, Germany.
AD  - Division of Hematology and Oncology, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, United States of America.
FAU - Pfeffer, Tobias J
AU  - Pfeffer TJ
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
FAU - Hilfiker, Andres
AU  - Hilfiker A
AD  - Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover 
      Medical School, Hanover, Germany.
FAU - Haverich, Axel
AU  - Haverich A
AD  - Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover 
      Medical School, Hanover, Germany.
FAU - Hilfiker-Kleiner, Denise
AU  - Hilfiker-Kleiner D
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hanover, 
      Germany.
AD  - Department of Cardiovascular Complications of Oncologic Therapies, Medical 
      Faculty of the Philipps University Marburg, Marburg, Germany.
LA  - eng
GR  - ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210804
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - COVID-19/blood/immunology/*pathology
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Dinoprostone/*blood/pharmacology/physiology
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - *Immunity/drug effects/physiology
MH  - Male
MH  - Middle Aged
MH  - SARS-CoV-2/drug effects/physiology
MH  - Vero Cells
MH  - Young Adult
PMC - PMC8336874
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/08/05 06:00
MHDA- 2021/08/14 06:00
PMCR- 2021/08/04
CRDT- 2021/08/04 17:21
PHST- 2021/03/11 00:00 [received]
PHST- 2021/07/14 00:00 [accepted]
PHST- 2021/08/04 17:21 [entrez]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2021/08/14 06:00 [medline]
PHST- 2021/08/04 00:00 [pmc-release]
AID - PONE-D-21-08028 [pii]
AID - 10.1371/journal.pone.0255335 [doi]
PST - epublish
SO  - PLoS One. 2021 Aug 4;16(8):e0255335. doi: 10.1371/journal.pone.0255335. 
      eCollection 2021.