Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients

The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrop...

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Published inVirology (New York, N.Y.) Vol. 563; pp. 74 - 81
Main Authors Abdelhafiz, Ahmed S., Fouad, Mariam A., Sayed-Ahmed, Mohamed M., Kamel, Mahmoud M., Ali, Asmaa, Fouda, Merhan, Khalil, Mahmoud A., Abdel-Moneim, Ahmed S., Kamal, Lamyaa M.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.11.2021
Subjects
Adult
biomarkers
COVID-19
COVID-19 - metabolism
COVID-19 infection
COX-2
Cytokines - metabolism
disease severity
Female
Forkhead Transcription Factors - metabolism
FOXP3
Humans
hypoxia
Hypoxia - metabolism
IFN-γ
IL-6
Infectious Disease
interleukin-6
Male
messenger RNA
Middle Aged
mortality
neutrophils
patients
Prognosis
quantitative polymerase chain reaction
RNA, Messenger - metabolism
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
TNFα
virology
COVID-19
SARS-CoV-2
IFN-γ
TNFα
Prognosis
COX-2
FOXP3
IL-6
Online AccessGet full text
ISSN0042-6822
1096-0341
1096-0341
DOI10.1016/j.virol.2021.08.012

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Abstract The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2. •The immunological response to SARS-CoV-2 infection is still obscure.•Low mRNA expressions of IFN-γ, TNFα and FOXP3 were detected in COVID-19 patients.•IL-6 and COX-2 are highly expressed in patients suffering from severe COVID-19.•FOXP3 can be used as a potential biomarker for predicting disease severity.•COVID-19 coincides with downregulation of FOXP3 and upregulations of IL-6 and COX-2.
AbstractList The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRᵀᴹ green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.
The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBR green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.
The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.
The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2. •The immunological response to SARS-CoV-2 infection is still obscure.•Low mRNA expressions of IFN-γ, TNFα and FOXP3 were detected in COVID-19 patients.•IL-6 and COX-2 are highly expressed in patients suffering from severe COVID-19.•FOXP3 can be used as a potential biomarker for predicting disease severity.•COVID-19 coincides with downregulation of FOXP3 and upregulations of IL-6 and COX-2.
AbstractThe levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBR TM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.
The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.
Author Kamal, Lamyaa M.
Kamel, Mahmoud M.
Khalil, Mahmoud A.
Abdelhafiz, Ahmed S.
Sayed-Ahmed, Mohamed M.
Fouda, Merhan
Abdel-Moneim, Ahmed S.
Fouad, Mariam A.
Ali, Asmaa
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  surname: Sayed-Ahmed
  fullname: Sayed-Ahmed, Mohamed M.
  organization: Pharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo University, Cairo, Egypt
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  givenname: Mahmoud M.
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  fullname: Khalil, Mahmoud A.
  organization: Department of Tropical Medicine and Infectious Disease, Imbaba Fever Hospital, MOH, Cairo, Egypt
– sequence: 8
  givenname: Ahmed S.
  orcidid: 0000-0002-3148-6782
  surname: Abdel-Moneim
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  organization: Microbiology Department, College of Medicine, Taif University, P.O. Box 1109, Taif, 21944, Saudi Arabia
– sequence: 9
  givenname: Lamyaa M.
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Cites_doi 10.1126/sciimmunol.abg5669
10.1378/chest.118.2.503
10.1016/j.thromres.2020.07.047
10.1038/nri2785
10.1016/j.metabol.2020.154262
10.1016/j.cellsig.2005.10.009
10.1007/s40618-020-01366-7
10.1126/science.abc6027
10.1016/S0140-6736(20)30183-5
10.3389/fimmu.2016.00604
10.1016/S0924-8579(98)00091-0
10.1056/NEJMoa2002032
10.1016/S0016-5085(99)70496-8
10.1006/meth.2001.1262
10.1002/eji.200838318
10.1152/ajpheart.01075.2008
10.3389/fimmu.2020.01446
10.1016/j.jinf.2020.06.008
10.1152/physiolgenomics.00131.2009
10.1016/j.jaci.2007.06.023
10.1016/j.ijantimicag.2020.105924
10.1016/j.jinf.2020.03.037
10.1038/s41467-021-22713-z
10.1073/pnas.1202366109
10.1002/jmv.25948
10.1111/imm.12388
10.1002/JLB.MR1217-481R
10.1038/s41591-020-0901-9
10.1111/j.1742-7843.2009.00395.x
10.1371/journal.pmed.1003321
10.1016/j.autrev.2020.102567
10.1111/j.1365-2249.2007.03299.x
10.1111/1348-0421.12168
10.1007/s00134-013-3036-3
10.1016/j.mehy.2020.110284
10.1038/mi.2014.33
10.1016/j.biocel.2006.02.003
10.1007/s00134-020-06065-8
10.1038/s41392-020-0148-4
10.1001/jama.2020.2648
10.1016/j.biopha.2018.10.014
10.1007/s00125-009-1374-z
10.1172/JCI137244
10.1183/13993003.02182-2020
10.3389/fimmu.2020.02167
10.1016/j.virol.2021.02.007
10.1096/fj.06-6589com
10.1002/jcph.1644
10.1038/s41591-020-0819-2
10.1002/mco2.12
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Keywords COVID-19
SARS-CoV-2
IFN-γ
TNFα
Prognosis
COX-2
FOXP3
IL-6
Language English
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References Hsu, Lai (bib23) 2018; 104
Bacchetta, Gambineri, Roncarolo (bib6) 2007; 120
Yu, Qin, Chen, Wang, Tian (bib56) 2020; 195
Dinarello (bib13) 2000; 118
Verrall (bib50) 2020; 11
Duque, Díaz-Muñoz, Fresno, Iñiguez (bib14) 2006; 18
Halter, Aimade, Barbié, Brisson, Rouby, Langeron, Klatzmann, Rosenzwajg, Monsel (bib21) 2020; 39
Shimizu (bib44) 2019
Wang, Fei, Li, Zhao, Yu (bib51) 2020; 46
Jamilloux, Henry, Belot, Viel, Fauter, El Jammal, Walzer, François, Sève (bib25) 2020; 19
Alexandre-Ramos, Silva-Carvalho, Lacerda, Serejo, Franco, Pereira, Carvalho, Neves, Saldanha-Araujo (bib4) 2018; 108
Mallajosyula, Ganjavi, Chakraborty, McSween, Pavlovitch-Bedzyk, Wilhelmy, Nau, Manohar, Nadeau, Davis (bib35) 2021; 6
Lai, Shih, Ko, Tang, Hsueh (bib27) 2020; 55
Palaiodimos, Kokkinidis, Li, Karamanis, Ognibene, Arora, Southern, Mantzoros (bib40) 2020; 108
Ben‐Shoshan, Maysel‐Auslender, Mor, Keren, George (bib7) 2008; 38
Stephen Victor, Das, Karnam, Pitard, Gautier, Bayry (bib46) 2020; 56
Harrison, Fazio-Eynullayeva, Lane, Underhill, Lip (bib22) 2020; 17
Liao, Liu, Yuan, Wen, Xu, Zhao, Cheng, Li, Wang, Wang, Liu, Amit, Zhang, Zhang (bib29) 2020; 26
Aggarwal, D'Alessio, Tsushima, Sidhaye, Cheadle, Grigoryev, Barnes, King (bib3) 2010; 41
Abdel-Moneim, Abdelwhab, Memish (bib1) 2021; 558
Luo, Zheng (bib33) 2016; 7
Ragab, Salah Eldin, Taeimah, Khattab, Salem (bib41) 2020; 11
Rysz, Al-Saadi, Sjöström, Farm, Campoccia Jalde, Plattén, Eriksson, Klein, Vargas-Paris, Nyrén, Abdula, Ouellette, Granberg, Jonsson Fagerlund, Lundberg (bib42) 2021; 12
Bruzzese, Lazzarino (bib8) 2020; 144
Galeotti, Bayry (bib16) 2020
Lee, Cheung, Peiris (bib28) 2013; 4
Huang, Wang, Li, Ren, Zhao, Hu, Zhang, Fan, Xu, Gu (bib24) 2020; 395
Tan, Wang, Zhang, Ding, Huang, Tang, Wang, Miao (bib48) 2020; 5
Grifoni, Valoriani, Cei, Lamanna, Gelli, Ciambotti, Vannucchi, Moroni, Pelagatti, Tarquini (bib18) 2020; 81
Liu, Qi, Bellanti, Moser, Ryffel, Zheng (bib31) 2020; 1
Wu, McGoogan (bib53) 2020; 323
Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui (bib19) 2020; 382
Mateu-Salat, Urgell, Chico (bib36) 2020; 43
Sakaguchi, Miyara, Costantino, Hafler (bib43) 2010; 10
Sugiyama, Shirai, Mukae, Ishimoto, Nagata, Sakamoto, Ishii, Nakayama, Yanagihara, Mizuta, Kohno (bib47) 2007; 147
Madec, Mallone, Afonso, Abou Mrad, Mesnier, Eljaafari, Thivolet (bib34) 2009; 52
Hadjadj, Yatim, Barnabei, Corneau, Boussier, Pere, Charbit, Bondet, Chenevier-Gobeaux, Breillat (bib20) 2020; 369
Adamzik, Broll, Steinmann, Westendorf, Rehfeld, Kreissig, Peters (bib2) 2013; 39
Gallelli, Zhang, Wang, Fu (bib17) 2020; 60
Mencarelli, Renga, Distrutti, Fiorucci (bib37) 2009; 296
Thevarajan, Nguyen, Koutsakos, Druce, Caly, van de Sandt, Jia, Nicholson, Catton, Cowie, Tong, Lewin, Kedzierska (bib49) 2020; 26
Livak, Schmittgen (bib32) 2001; 25
Daneshmand, Saliminejad, Dehghan Shasaltaneh, Kamali, Riazi, Nazari, Azimzadeh, Khorram Khorshid (bib12) 2016; 8
Khan, Slifer, Araujo, Remington (bib26) 1999; 11
Neildez‐Nguyen, Bigot, Da Rocha, Corre, Boisgerault, Paldi, Galy (bib39) 2015; 144
Srivastava, Jha, Salhan, Mittal (bib45) 2009; 104
Chen, Wu, Guo, Cao, Huang, Wang, Wang, Zhang, Chen, Yu (bib9) 2020; 130
Conti, Younes (bib11) 2020; 34
Yan, Hao, Mu, Timani, Ye, Zhu, Wu (bib54) 2006; 38
Fu, Ramanujam, Wong, Fantry, Drachenberg, James, Meltzer, Wilson (bib15) 1999; 116
Wu, Cui, Zhu, Wang, Li, Wang (bib52) 2014; 58
Ye, Wang, Mao (bib55) 2020; 80
Aziz, Fatima, Assaly (bib5) 2020; 92
Clambey, McNamee, Westrich, Glover, Campbell, Jedlicka, de Zoeten, Cambier, Stenmark, Colgan (bib10) 2012; 109
Liu, Yang, Gu, Yue, Wu, Wu, Zhu (bib30) 2007; 21
Mock, Garibaldi, Aggarwal, Jenkins, Limjunyawong, Singer, Chau, Rabold, Files, Sidhaye (bib38) 2014; 7
Mateu-Salat (10.1016/j.virol.2021.08.012_bib36) 2020; 43
Harrison (10.1016/j.virol.2021.08.012_bib22) 2020; 17
Guan (10.1016/j.virol.2021.08.012_bib19) 2020; 382
Yan (10.1016/j.virol.2021.08.012_bib54) 2006; 38
Fu (10.1016/j.virol.2021.08.012_bib15) 1999; 116
Jamilloux (10.1016/j.virol.2021.08.012_bib25) 2020; 19
Stephen Victor (10.1016/j.virol.2021.08.012_bib46) 2020; 56
Neildez‐Nguyen (10.1016/j.virol.2021.08.012_bib39) 2015; 144
Ye (10.1016/j.virol.2021.08.012_bib55) 2020; 80
Grifoni (10.1016/j.virol.2021.08.012_bib18) 2020; 81
Clambey (10.1016/j.virol.2021.08.012_bib10) 2012; 109
Abdel-Moneim (10.1016/j.virol.2021.08.012_bib1) 2021; 558
Aggarwal (10.1016/j.virol.2021.08.012_bib3) 2010; 41
Lai (10.1016/j.virol.2021.08.012_bib27) 2020; 55
Verrall (10.1016/j.virol.2021.08.012_bib50) 2020; 11
Halter (10.1016/j.virol.2021.08.012_bib21) 2020; 39
Duque (10.1016/j.virol.2021.08.012_bib14) 2006; 18
Madec (10.1016/j.virol.2021.08.012_bib34) 2009; 52
Luo (10.1016/j.virol.2021.08.012_bib33) 2016; 7
Wang (10.1016/j.virol.2021.08.012_bib51) 2020; 46
Lee (10.1016/j.virol.2021.08.012_bib28) 2013; 4
Mencarelli (10.1016/j.virol.2021.08.012_bib37) 2009; 296
Bacchetta (10.1016/j.virol.2021.08.012_bib6) 2007; 120
Chen (10.1016/j.virol.2021.08.012_bib9) 2020; 130
Ben‐Shoshan (10.1016/j.virol.2021.08.012_bib7) 2008; 38
Bruzzese (10.1016/j.virol.2021.08.012_bib8) 2020; 144
Wu (10.1016/j.virol.2021.08.012_bib53) 2020; 323
Livak (10.1016/j.virol.2021.08.012_bib32) 2001; 25
Liu (10.1016/j.virol.2021.08.012_bib31) 2020; 1
Ragab (10.1016/j.virol.2021.08.012_bib41) 2020; 11
Srivastava (10.1016/j.virol.2021.08.012_bib45) 2009; 104
Hsu (10.1016/j.virol.2021.08.012_bib23) 2018; 104
Thevarajan (10.1016/j.virol.2021.08.012_bib49) 2020; 26
Wu (10.1016/j.virol.2021.08.012_bib52) 2014; 58
Tan (10.1016/j.virol.2021.08.012_bib48) 2020; 5
Mallajosyula (10.1016/j.virol.2021.08.012_bib35) 2021; 6
Yu (10.1016/j.virol.2021.08.012_bib56) 2020; 195
Aziz (10.1016/j.virol.2021.08.012_bib5) 2020; 92
Galeotti (10.1016/j.virol.2021.08.012_bib16) 2020
Sugiyama (10.1016/j.virol.2021.08.012_bib47) 2007; 147
Palaiodimos (10.1016/j.virol.2021.08.012_bib40) 2020; 108
Khan (10.1016/j.virol.2021.08.012_bib26) 1999; 11
Hadjadj (10.1016/j.virol.2021.08.012_bib20) 2020; 369
Liao (10.1016/j.virol.2021.08.012_bib29) 2020; 26
Sakaguchi (10.1016/j.virol.2021.08.012_bib43) 2010; 10
Gallelli (10.1016/j.virol.2021.08.012_bib17) 2020; 60
Shimizu (10.1016/j.virol.2021.08.012_bib44) 2019
Alexandre-Ramos (10.1016/j.virol.2021.08.012_bib4) 2018; 108
Dinarello (10.1016/j.virol.2021.08.012_bib13) 2000; 118
Adamzik (10.1016/j.virol.2021.08.012_bib2) 2013; 39
Daneshmand (10.1016/j.virol.2021.08.012_bib12) 2016; 8
Liu (10.1016/j.virol.2021.08.012_bib30) 2007; 21
Mock (10.1016/j.virol.2021.08.012_bib38) 2014; 7
Rysz (10.1016/j.virol.2021.08.012_bib42) 2021; 12
Conti (10.1016/j.virol.2021.08.012_bib11) 2020; 34
Huang (10.1016/j.virol.2021.08.012_bib24) 2020; 395
References_xml – volume: 395
  start-page: 497
  year: 2020
  end-page: 506
  ident: bib24
  article-title: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
  publication-title: Lancet
– volume: 147
  start-page: 540
  year: 2007
  end-page: 546
  ident: bib47
  article-title: Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells
  publication-title: Clin. Exp. Immunol.
– volume: 56
  year: 2020
  ident: bib46
  article-title: Potential of regulatory T-cell-based therapies in the management of severe COVID-19
  publication-title: Eur. Respir. J.
– volume: 26
  start-page: 842
  year: 2020
  end-page: 844
  ident: bib29
  article-title: Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
  publication-title: Nat. Med.
– volume: 43
  start-page: 1527
  year: 2020
  end-page: 1528
  ident: bib36
  article-title: SARS-COV-2 as a trigger for autoimmune disease: report of two cases of Graves' disease after COVID-19
  publication-title: J. Endocrinol. Invest.
– volume: 55
  start-page: 105924
  year: 2020
  ident: bib27
  article-title: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges
  publication-title: Int. J. Antimicrob. Agents
– volume: 11
  start-page: 2167
  year: 2020
  ident: bib50
  article-title: Scientific rationale for a bottom-up approach to target the host response in order to try and reduce the numbers presenting with adult respiratory distress syndrome associated with COVID-19. Is there a role for statins and COX-2 inhibitors in the prevention and early treatment of the disease?
  publication-title: Front. Immunol.
– volume: 6
  year: 2021
  ident: bib35
  article-title: CD8(+) T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients
  publication-title: Sci. Immunol.
– volume: 108
  start-page: 154262
  year: 2020
  ident: bib40
  article-title: Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx
  publication-title: Metabolism
– volume: 80
  start-page: 607
  year: 2020
  end-page: 613
  ident: bib55
  article-title: The pathogenesis and treatment of the Cytokine Storm'in COVID-19
  publication-title: J. Infect.
– volume: 19
  start-page: 102567
  year: 2020
  ident: bib25
  article-title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions
  publication-title: Autoimmun. Rev.
– volume: 130
  year: 2020
  ident: bib9
  article-title: Clinical and immunological features of severe and moderate coronavirus disease 2019
  publication-title: J. Clin. Invest.
– volume: 81
  start-page: 452
  year: 2020
  end-page: 482
  ident: bib18
  article-title: Interleukin-6 as prognosticator in patients with COVID-19: IL-6 and Covid-19
  publication-title: J. Infect.
– volume: 21
  start-page: 1586
  year: 2007
  end-page: 1596
  ident: bib30
  article-title: Spike protein of SARS‐CoV stimulates cyclooxygenase‐2 expression via both calcium‐dependent and calcium‐independent protein kinase C pathways
  publication-title: Faseb. J.
– start-page: 31
  year: 2019
  end-page: 41
  ident: bib44
  article-title: Clinical Features of Cytokine Storm Syndrome, Cytokine Storm Syndrome
– volume: 116
  start-page: 1319
  year: 1999
  end-page: 1329
  ident: bib15
  article-title: Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis
  publication-title: Gastroenterology
– volume: 60
  start-page: 815
  year: 2020
  end-page: 825
  ident: bib17
  article-title: Severe acute lung injury related to COVID-19 infection: a review and the possible role for escin
  publication-title: J. Clin. Pharmacol.
– volume: 34
  start-page: 71
  year: 2020
  ident: bib11
  article-title: Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection
  publication-title: J. Biol. Regul. Homeost. Agents
– volume: 8
  start-page: 120
  year: 2016
  end-page: 125
  ident: bib12
  article-title: Neuroprotective effects of herbal extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on rat model of sporadic alzheimer's disease
  publication-title: Avicenna J. Med. Biotechnol. (AJMB)
– volume: 18
  start-page: 1262
  year: 2006
  end-page: 1269
  ident: bib14
  article-title: Up-regulation of cyclooxygenase-2 by interleukin-1beta in colon carcinoma cells
  publication-title: Cell. Signal.
– volume: 52
  start-page: 1391
  year: 2009
  end-page: 1399
  ident: bib34
  article-title: Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells
  publication-title: Diabetologia
– volume: 7
  start-page: 1440
  year: 2014
  end-page: 1451
  ident: bib38
  article-title: Foxp3+ regulatory T cells promote lung epithelial proliferation
  publication-title: Mucosal Immunol.
– volume: 296
  start-page: H272
  year: 2009
  end-page: H281
  ident: bib37
  article-title: Antiatherosclerotic effect of farnesoid X receptor
  publication-title: Am. J. Physiol. Heart Circ. Physiol.
– volume: 558
  start-page: 1
  year: 2021
  end-page: 12
  ident: bib1
  article-title: Insights into SARS-CoV-2 evolution, potential antivirals, and vaccines
  publication-title: Virology
– volume: 7
  start-page: 604
  year: 2016
  ident: bib33
  article-title: Hall of fame among pro-inflammatory cytokines: interleukin-6 gene and its transcriptional regulation mechanisms
  publication-title: Front. Immunol.
– volume: 144
  start-page: 431
  year: 2015
  end-page: 443
  ident: bib39
  article-title: Hypoxic culture conditions enhance the generation of regulatory T cells
  publication-title: Immunology
– volume: 12
  start-page: 2417
  year: 2021
  ident: bib42
  article-title: COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
  publication-title: Nat. Commun.
– volume: 120
  start-page: 227
  year: 2007
  end-page: 235
  ident: bib6
  article-title: Role of regulatory T cells and FOXP3 in human diseases
  publication-title: J. Allergy Clin. Immunol.
– volume: 118
  start-page: 503
  year: 2000
  end-page: 508
  ident: bib13
  article-title: Proinflammatory cytokines
  publication-title: Chest
– volume: 41
  start-page: 109
  year: 2010
  end-page: 119
  ident: bib3
  article-title: Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling
  publication-title: Physiol. Genom.
– volume: 5
  start-page: 33
  year: 2020
  ident: bib48
  article-title: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study
  publication-title: Signal Transduct. Target Ther.
– volume: 369
  start-page: 718
  year: 2020
  end-page: 724
  ident: bib20
  article-title: Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients
  publication-title: Science
– volume: 39
  start-page: 35
  year: 2020
  end-page: 44
  ident: bib21
  article-title: T regulatory cells activation and distribution are modified in critically ill patients with acute respiratory distress syndrome: a prospective single-centre observational study
  publication-title: Anaesth. Crit. Care Pain Med.
– volume: 104
  start-page: 478
  year: 2009
  end-page: 482
  ident: bib45
  article-title: Azithromycin treatment modulates cytokine production in Chlamydia trachomatis infected women
  publication-title: Basic Clin. Pharmacol. Toxicol.
– volume: 4
  start-page: 29
  year: 2013
  end-page: 35
  ident: bib28
  article-title: Role of cyclooxygenase-2 in H5N1 viral pathogenesis and the potential use of its inhibitors
  publication-title: Hong Kong Med. J.
– volume: 10
  start-page: 490
  year: 2010
  end-page: 500
  ident: bib43
  article-title: FOXP3+ regulatory T cells in the human immune system
  publication-title: Nat. Rev. Immunol.
– volume: 46
  start-page: 1475
  year: 2020
  end-page: 1476
  ident: bib51
  article-title: IL-6 may be a good biomarker for earlier detection of COVID-19 progression
  publication-title: Intensive Care Med.
– volume: 382
  start-page: 1708
  year: 2020
  end-page: 1720
  ident: bib19
  article-title: Clinical characteristics of coronavirus disease 2019 in China
  publication-title: N. Engl. J. Med.
– volume: 25
  start-page: 402
  year: 2001
  end-page: 408
  ident: bib32
  article-title: Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method
  publication-title: Methods
– volume: 144
  year: 2020
  ident: bib8
  article-title: The paradoxical effect of IL-6 and implications for the use of Tocilizumab in Covid-19 patients
  publication-title: Med. Hypotheses
– volume: 11
  start-page: 1446
  year: 2020
  ident: bib41
  article-title: The COVID-19 cytokine storm; what we know so far
  publication-title: Front. Immunol.
– volume: 195
  start-page: 219
  year: 2020
  end-page: 225
  ident: bib56
  article-title: D-dimer level is associated with the severity of COVID-19
  publication-title: Thromb. Res.
– volume: 11
  start-page: 121
  year: 1999
  end-page: 132
  ident: bib26
  article-title: Effect of clarithromycin and azithromycin on production of cytokines by human monocytes
  publication-title: Int. J. Antimicrob. Agents
– volume: 58
  start-page: 409
  year: 2014
  end-page: 415
  ident: bib52
  article-title: Effect of HIF1α on Foxp3 expression in CD4+ CD25− T lymphocytes
  publication-title: Microbiol. Immunol.
– volume: 38
  start-page: 1417
  year: 2006
  end-page: 1428
  ident: bib54
  article-title: Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein
  publication-title: Int. J. Biochem. Cell Biol.
– volume: 39
  start-page: 1743
  year: 2013
  end-page: 1751
  ident: bib2
  article-title: An increased alveolar CD4+ CD25+ Foxp3+ T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality
  publication-title: Intensive Care Med.
– volume: 17
  year: 2020
  ident: bib22
  article-title: Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: a federated electronic medical record analysis
  publication-title: PLoS Med.
– volume: 323
  start-page: 1239
  year: 2020
  end-page: 1242
  ident: bib53
  article-title: Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention
  publication-title: JAMA
– volume: 92
  start-page: 2283
  year: 2020
  end-page: 2285
  ident: bib5
  article-title: Elevated interleukin‐6 and severe COVID‐19: a meta‐analysis
  publication-title: J. Med. Virol.
– start-page: 1
  year: 2020
  end-page: 2
  ident: bib16
  article-title: Autoimmune and inflammatory diseases following COVID-19
  publication-title: Nat. Rev. Rheumatol.
– volume: 108
  start-page: 1584
  year: 2018
  end-page: 1590
  ident: bib4
  article-title: LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation
  publication-title: Biomed. Pharmacother. Biomed. pharmacother.
– volume: 109
  year: 2012
  ident: bib10
  article-title: Hypoxia-inducible factor-1 alpha–dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa
  publication-title: Proc. Natl. Acad. Sci. U.S.A.
– volume: 26
  start-page: 453
  year: 2020
  end-page: 455
  ident: bib49
  article-title: Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19
  publication-title: Nat. Med.
– volume: 38
  start-page: 2412
  year: 2008
  end-page: 2418
  ident: bib7
  article-title: Hypoxia controls CD4+ CD25+ regulatory T‐cell homeostasis via hypoxia‐inducible factor‐1α
  publication-title: Eur. J. Iimmunol.
– volume: 104
  start-page: 911
  year: 2018
  end-page: 918
  ident: bib23
  article-title: Hypoxia‐inducible factor 1α plays a predominantly negative role in regulatory T cell functions
  publication-title: J. Leukoc. Biol.
– volume: 1
  start-page: 157
  year: 2020
  end-page: 164
  ident: bib31
  article-title: Regulatory T cells: a potential weapon to combat COVID‐19?
  publication-title: MedComm
– volume: 34
  start-page: 71
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib11
  article-title: Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection
  publication-title: J. Biol. Regul. Homeost. Agents
– volume: 6
  year: 2021
  ident: 10.1016/j.virol.2021.08.012_bib35
  article-title: CD8(+) T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients
  publication-title: Sci. Immunol.
  doi: 10.1126/sciimmunol.abg5669
– volume: 118
  start-page: 503
  year: 2000
  ident: 10.1016/j.virol.2021.08.012_bib13
  article-title: Proinflammatory cytokines
  publication-title: Chest
  doi: 10.1378/chest.118.2.503
– volume: 195
  start-page: 219
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib56
  article-title: D-dimer level is associated with the severity of COVID-19
  publication-title: Thromb. Res.
  doi: 10.1016/j.thromres.2020.07.047
– volume: 10
  start-page: 490
  year: 2010
  ident: 10.1016/j.virol.2021.08.012_bib43
  article-title: FOXP3+ regulatory T cells in the human immune system
  publication-title: Nat. Rev. Immunol.
  doi: 10.1038/nri2785
– volume: 108
  start-page: 154262
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib40
  article-title: Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx
  publication-title: Metabolism
  doi: 10.1016/j.metabol.2020.154262
– volume: 18
  start-page: 1262
  year: 2006
  ident: 10.1016/j.virol.2021.08.012_bib14
  article-title: Up-regulation of cyclooxygenase-2 by interleukin-1beta in colon carcinoma cells
  publication-title: Cell. Signal.
  doi: 10.1016/j.cellsig.2005.10.009
– volume: 43
  start-page: 1527
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib36
  article-title: SARS-COV-2 as a trigger for autoimmune disease: report of two cases of Graves' disease after COVID-19
  publication-title: J. Endocrinol. Invest.
  doi: 10.1007/s40618-020-01366-7
– volume: 369
  start-page: 718
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib20
  article-title: Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients
  publication-title: Science
  doi: 10.1126/science.abc6027
– start-page: 31
  year: 2019
  ident: 10.1016/j.virol.2021.08.012_bib44
– volume: 395
  start-page: 497
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib24
  article-title: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
  publication-title: Lancet
  doi: 10.1016/S0140-6736(20)30183-5
– volume: 7
  start-page: 604
  year: 2016
  ident: 10.1016/j.virol.2021.08.012_bib33
  article-title: Hall of fame among pro-inflammatory cytokines: interleukin-6 gene and its transcriptional regulation mechanisms
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2016.00604
– volume: 11
  start-page: 121
  year: 1999
  ident: 10.1016/j.virol.2021.08.012_bib26
  article-title: Effect of clarithromycin and azithromycin on production of cytokines by human monocytes
  publication-title: Int. J. Antimicrob. Agents
  doi: 10.1016/S0924-8579(98)00091-0
– volume: 382
  start-page: 1708
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib19
  article-title: Clinical characteristics of coronavirus disease 2019 in China
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa2002032
– volume: 116
  start-page: 1319
  year: 1999
  ident: 10.1016/j.virol.2021.08.012_bib15
  article-title: Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis
  publication-title: Gastroenterology
  doi: 10.1016/S0016-5085(99)70496-8
– volume: 25
  start-page: 402
  year: 2001
  ident: 10.1016/j.virol.2021.08.012_bib32
  article-title: Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method
  publication-title: Methods
  doi: 10.1006/meth.2001.1262
– volume: 38
  start-page: 2412
  year: 2008
  ident: 10.1016/j.virol.2021.08.012_bib7
  article-title: Hypoxia controls CD4+ CD25+ regulatory T‐cell homeostasis via hypoxia‐inducible factor‐1α
  publication-title: Eur. J. Iimmunol.
  doi: 10.1002/eji.200838318
– volume: 296
  start-page: H272
  year: 2009
  ident: 10.1016/j.virol.2021.08.012_bib37
  article-title: Antiatherosclerotic effect of farnesoid X receptor
  publication-title: Am. J. Physiol. Heart Circ. Physiol.
  doi: 10.1152/ajpheart.01075.2008
– volume: 11
  start-page: 1446
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib41
  article-title: The COVID-19 cytokine storm; what we know so far
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2020.01446
– volume: 81
  start-page: 452
  issue: 3
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib18
  article-title: Interleukin-6 as prognosticator in patients with COVID-19: IL-6 and Covid-19
  publication-title: J. Infect.
  doi: 10.1016/j.jinf.2020.06.008
– volume: 41
  start-page: 109
  year: 2010
  ident: 10.1016/j.virol.2021.08.012_bib3
  article-title: Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling
  publication-title: Physiol. Genom.
  doi: 10.1152/physiolgenomics.00131.2009
– volume: 120
  start-page: 227
  year: 2007
  ident: 10.1016/j.virol.2021.08.012_bib6
  article-title: Role of regulatory T cells and FOXP3 in human diseases
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/j.jaci.2007.06.023
– volume: 55
  start-page: 105924
  issue: 3
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib27
  article-title: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges
  publication-title: Int. J. Antimicrob. Agents
  doi: 10.1016/j.ijantimicag.2020.105924
– volume: 80
  start-page: 607
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib55
  article-title: The pathogenesis and treatment of the Cytokine Storm'in COVID-19
  publication-title: J. Infect.
  doi: 10.1016/j.jinf.2020.03.037
– volume: 12
  start-page: 2417
  year: 2021
  ident: 10.1016/j.virol.2021.08.012_bib42
  article-title: COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-22713-z
– volume: 109
  year: 2012
  ident: 10.1016/j.virol.2021.08.012_bib10
  article-title: Hypoxia-inducible factor-1 alpha–dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa
  publication-title: Proc. Natl. Acad. Sci. U.S.A.
  doi: 10.1073/pnas.1202366109
– volume: 92
  start-page: 2283
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib5
  article-title: Elevated interleukin‐6 and severe COVID‐19: a meta‐analysis
  publication-title: J. Med. Virol.
  doi: 10.1002/jmv.25948
– volume: 144
  start-page: 431
  year: 2015
  ident: 10.1016/j.virol.2021.08.012_bib39
  article-title: Hypoxic culture conditions enhance the generation of regulatory T cells
  publication-title: Immunology
  doi: 10.1111/imm.12388
– volume: 104
  start-page: 911
  year: 2018
  ident: 10.1016/j.virol.2021.08.012_bib23
  article-title: Hypoxia‐inducible factor 1α plays a predominantly negative role in regulatory T cell functions
  publication-title: J. Leukoc. Biol.
  doi: 10.1002/JLB.MR1217-481R
– volume: 26
  start-page: 842
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib29
  article-title: Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
  publication-title: Nat. Med.
  doi: 10.1038/s41591-020-0901-9
– volume: 104
  start-page: 478
  year: 2009
  ident: 10.1016/j.virol.2021.08.012_bib45
  article-title: Azithromycin treatment modulates cytokine production in Chlamydia trachomatis infected women
  publication-title: Basic Clin. Pharmacol. Toxicol.
  doi: 10.1111/j.1742-7843.2009.00395.x
– volume: 17
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib22
  article-title: Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: a federated electronic medical record analysis
  publication-title: PLoS Med.
  doi: 10.1371/journal.pmed.1003321
– volume: 19
  start-page: 102567
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib25
  article-title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions
  publication-title: Autoimmun. Rev.
  doi: 10.1016/j.autrev.2020.102567
– volume: 147
  start-page: 540
  year: 2007
  ident: 10.1016/j.virol.2021.08.012_bib47
  article-title: Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells
  publication-title: Clin. Exp. Immunol.
  doi: 10.1111/j.1365-2249.2007.03299.x
– volume: 58
  start-page: 409
  year: 2014
  ident: 10.1016/j.virol.2021.08.012_bib52
  article-title: Effect of HIF1α on Foxp3 expression in CD4+ CD25− T lymphocytes
  publication-title: Microbiol. Immunol.
  doi: 10.1111/1348-0421.12168
– volume: 39
  start-page: 1743
  year: 2013
  ident: 10.1016/j.virol.2021.08.012_bib2
  article-title: An increased alveolar CD4+ CD25+ Foxp3+ T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality
  publication-title: Intensive Care Med.
  doi: 10.1007/s00134-013-3036-3
– volume: 144
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib8
  article-title: The paradoxical effect of IL-6 and implications for the use of Tocilizumab in Covid-19 patients
  publication-title: Med. Hypotheses
  doi: 10.1016/j.mehy.2020.110284
– volume: 8
  start-page: 120
  year: 2016
  ident: 10.1016/j.virol.2021.08.012_bib12
  article-title: Neuroprotective effects of herbal extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on rat model of sporadic alzheimer's disease
  publication-title: Avicenna J. Med. Biotechnol. (AJMB)
– volume: 7
  start-page: 1440
  year: 2014
  ident: 10.1016/j.virol.2021.08.012_bib38
  article-title: Foxp3+ regulatory T cells promote lung epithelial proliferation
  publication-title: Mucosal Immunol.
  doi: 10.1038/mi.2014.33
– volume: 39
  start-page: 35
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib21
  article-title: T regulatory cells activation and distribution are modified in critically ill patients with acute respiratory distress syndrome: a prospective single-centre observational study
  publication-title: Anaesth. Crit. Care Pain Med.
– volume: 38
  start-page: 1417
  year: 2006
  ident: 10.1016/j.virol.2021.08.012_bib54
  article-title: Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein
  publication-title: Int. J. Biochem. Cell Biol.
  doi: 10.1016/j.biocel.2006.02.003
– volume: 46
  start-page: 1475
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib51
  article-title: IL-6 may be a good biomarker for earlier detection of COVID-19 progression
  publication-title: Intensive Care Med.
  doi: 10.1007/s00134-020-06065-8
– volume: 5
  start-page: 33
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib48
  article-title: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study
  publication-title: Signal Transduct. Target Ther.
  doi: 10.1038/s41392-020-0148-4
– volume: 323
  start-page: 1239
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib53
  article-title: Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention
  publication-title: JAMA
  doi: 10.1001/jama.2020.2648
– volume: 108
  start-page: 1584
  year: 2018
  ident: 10.1016/j.virol.2021.08.012_bib4
  article-title: LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation
  publication-title: Biomed. Pharmacother. Biomed. pharmacother.
  doi: 10.1016/j.biopha.2018.10.014
– volume: 52
  start-page: 1391
  year: 2009
  ident: 10.1016/j.virol.2021.08.012_bib34
  article-title: Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells
  publication-title: Diabetologia
  doi: 10.1007/s00125-009-1374-z
– volume: 130
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib9
  article-title: Clinical and immunological features of severe and moderate coronavirus disease 2019
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI137244
– volume: 56
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib46
  article-title: Potential of regulatory T-cell-based therapies in the management of severe COVID-19
  publication-title: Eur. Respir. J.
  doi: 10.1183/13993003.02182-2020
– volume: 11
  start-page: 2167
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib50
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2020.02167
– volume: 558
  start-page: 1
  year: 2021
  ident: 10.1016/j.virol.2021.08.012_bib1
  article-title: Insights into SARS-CoV-2 evolution, potential antivirals, and vaccines
  publication-title: Virology
  doi: 10.1016/j.virol.2021.02.007
– volume: 21
  start-page: 1586
  year: 2007
  ident: 10.1016/j.virol.2021.08.012_bib30
  article-title: Spike protein of SARS‐CoV stimulates cyclooxygenase‐2 expression via both calcium‐dependent and calcium‐independent protein kinase C pathways
  publication-title: Faseb. J.
  doi: 10.1096/fj.06-6589com
– volume: 60
  start-page: 815
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib17
  article-title: Severe acute lung injury related to COVID-19 infection: a review and the possible role for escin
  publication-title: J. Clin. Pharmacol.
  doi: 10.1002/jcph.1644
– start-page: 1
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib16
  article-title: Autoimmune and inflammatory diseases following COVID-19
  publication-title: Nat. Rev. Rheumatol.
– volume: 4
  start-page: 29
  issue: 19
  year: 2013
  ident: 10.1016/j.virol.2021.08.012_bib28
  article-title: Role of cyclooxygenase-2 in H5N1 viral pathogenesis and the potential use of its inhibitors
  publication-title: Hong Kong Med. J.
– volume: 26
  start-page: 453
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib49
  article-title: Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19
  publication-title: Nat. Med.
  doi: 10.1038/s41591-020-0819-2
– volume: 1
  start-page: 157
  year: 2020
  ident: 10.1016/j.virol.2021.08.012_bib31
  article-title: Regulatory T cells: a potential weapon to combat COVID‐19?
  publication-title: MedComm
  doi: 10.1002/mco2.12
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Snippet The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using...
AbstractThe levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated...
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StartPage 74
SubjectTerms Adult
biomarkers
COVID-19
COVID-19 - metabolism
COVID-19 infection
COX-2
Cytokines - metabolism
disease severity
Female
Forkhead Transcription Factors - metabolism
FOXP3
Humans
hypoxia
Hypoxia - metabolism
IFN-γ
IL-6
Infectious Disease
interleukin-6
Male
messenger RNA
Middle Aged
mortality
neutrophils
patients
Prognosis
quantitative polymerase chain reaction
RNA, Messenger - metabolism
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
TNFα
virology
Title Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients
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https://dx.doi.org/10.1016/j.virol.2021.08.012
https://www.ncbi.nlm.nih.gov/pubmed/34478955
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https://www.proquest.com/docview/2636496732
https://pubmed.ncbi.nlm.nih.gov/PMC8397927
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