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Article ; Online: Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19.

2021 Volume 13, Issue 2

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adult ; Aged ; Bradykinin/analogs & derivatives ; Bradykinin/therapeutic use ; COVID-19/drug therapy ; Case-Control Studies ; Complement C1 Inhibitor Protein/therapeutic use ; Drug Repositioning ; Female ; Humans ; Kallikrein-Kinin System/drug effects ; Kallikreins/antagonists & inhibitors ; Lung/drug effects ; Lung/pathology ; Male ; Middle Aged
Chemical Substances	Complement C1 Inhibitor Protein ; icatibant (7PG89G35Q7) ; Kallikreins (EC 3.4.21.-) ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2021-02-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13020309
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines

de Souza, William M. / Muraro, Stéfanie P. / Souza, Gabriela F. / Amorim, Mariene R. / Sesti-Costa, Renata / Mofatto, Luciana S. / Forato, Julia / Barbosa, Priscilla P. / Toledo-Teixeira, Daniel A. / Bispo-dos-Santos, Karina / Parise, Pierina L. / Brunetti, Natalia S. / Moreira, Joselia C. O. / Costa, Vitor A. / Cardozo, Daniela M. / Moretti, Maria L. / Barros-Mazon, Silvia / Marchesi, Gabriela F. / Ambrosio, Christiane /

Spilki, Fernando R. / Almeida, Valeria C. / Vieira, Andre S. / Zambon, Lair / Farias, Alessandro S. / Addas-Carvalho, Marcelo / Benites, Bruno D. / Marques, Rafael E. / Sabino, Ester C. / Zuben, Andrea B. Von / Weaver, Scott C. / Faria, Nuno R. / Granja, Fabiana / Angerami, Rodrigo N. / Proença-Módena, José Luiz

Viruses. 2021 Oct. 22, v. 13, no. 11

2021

Abstract: A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, ...

Abstract	A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8–3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.
Keywords	RNA ; Severe acute respiratory syndrome coronavirus 2 ; blood serum ; death ; disease severity ; elderly ; inactivated vaccines ; mortality ; risk reduction ; vaccination
Language	English
Dates of publication	2021-1022
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112127
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pharmacological inhibition of the kinin-kallikrein system in severe COVID-19 A proof-of-concept study

medRxiv

Abstract: Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only ... ...

Abstract	Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.
Keywords	covid19
Language	English
Publishing date	2020-08-14
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.08.11.20167353
Database	COVID19

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Article ; Online: Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines.

de Souza, William M / Muraro, Stéfanie P / Souza, Gabriela F / Amorim, Mariene R / Sesti-Costa, Renata / Mofatto, Luciana S / Forato, Julia / Barbosa, Priscilla P / Toledo-Teixeira, Daniel A / Bispo-Dos-Santos, Karina / Parise, Pierina L / Brunetti, Natalia S / Moreira, Joselia C O / Costa, Vitor A / Cardozo, Daniela M / Moretti, Maria L / Barros-Mazon, Silvia / Marchesi, Gabriela F / Ambrosio, Christiane /

Spilki, Fernando R / Almeida, Valeria C / Vieira, Andre S / Zambon, Lair / Farias, Alessandro S / Addas-Carvalho, Marcelo / Benites, Bruno D / Marques, Rafael E / Sabino, Ester C / Zuben, Andrea B Von / Weaver, Scott C / Faria, Nuno R / Granja, Fabiana / Angerami, Rodrigo N / Proença-Módena, José Luiz

Viruses

2021 Volume 13, Issue 11

Abstract	A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A,
MeSH term(s)	Adenoviridae ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology ; Brazil/epidemiology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Serological Testing ; COVID-19 Vaccines ; Cohort Studies ; Disease Outbreaks/statistics & numerical data ; Female ; Genetic Vectors ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; RNA, Viral ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; Vaccination ; Vaccines, Inactivated ; Whole Genome Sequencing ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; COVID-19 Vaccines ; Immunoglobulin G ; RNA, Viral ; Vaccines, Inactivated
Language	English
Publishing date	2021-10-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112127
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Article ; Online: Respiratory Viral Shedding in Healthcare Workers Reinfected with SARS-CoV-2, Brazil, 2020.

Amorim, Mariene R / Souza, William M / Barros, Antonio C G / Toledo-Teixeira, Daniel A / Dos-Santos, Karina Bispo / Simeoni, Camila L / Parise, Pierina L / Vieira, Aline / Forato, Julia / Claro, Ingra M / Mofatto, Luciana S / Barbosa, Priscila P / Brunetti, Natalia S / França, Emerson S S / Pedroso, Gisele A / Carvalho, Barbara F N / Zaccariotto, Tania R / Krywacz, Kamila C S / Vieira, André S /

Mori, Marcelo A / Farias, Alessandro S / Pavan, Maria H P / Bachur, Luís Felipe / Cardoso, Luís G O / Spilki, Fernando R / Sabino, Ester C / Faria, Nuno R / Santos, Magnun N N / Angerami, Rodrigo / Leme, Patricia A F / Schreiber, Angelica / Moretti, Maria L / Granja, Fabiana / Proenca-Modena, José Luiz

Emerging infectious diseases

2021 Volume 27, Issue 6, Page(s) 1737–1740

Abstract: We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection ... ...

Abstract	We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.
MeSH term(s)	Adult ; Brazil/epidemiology ; COVID-19/diagnosis ; COVID-19/epidemiology ; Female ; Health Personnel ; Humans ; Middle Aged ; Reinfection/diagnosis ; Reinfection/therapy ; Reinfection/virology ; SARS-CoV-2/isolation & purification ; Virus Shedding
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2706.210558
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Article ; Online: SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

Brunetti, Natalia S / Davanzo, Gustavo G / de Moraes, Diogo / Ferrari, Allan J R / Souza, Gabriela F / Muraro, Stéfanie Primon / Knittel, Thiago L / Boldrini, Vinicius O / Monteiro, Lauar B / Virgílio-da-Silva, João Victor / Profeta, Gerson S / Wassano, Natália S / Nunes Santos, Luana / Carregari, Victor C / Dias, Artur H S / Veras, Flavio P / Tavares, Lucas A / Forato, Julia / Castro, Icaro M S /

Silva-Costa, Lícia C / Palma, André C / Mansour, Eli / Ulaf, Raisa G / Bernardes, Ana F / Nunes, Thyago A / Ribeiro, Luciana C / Agrela, Marcus V / Moretti, Maria Luiza / Buscaratti, Lucas I / Crunfli, Fernanda / Ludwig, Raissa G / Gerhardt, Jaqueline A / Munhoz-Alves, Natália / Marques, Ana Maria / Sesti-Costa, Renata / Amorim, Mariene R / Toledo-Teixeira, Daniel A / Parise, Pierina Lorencini / Martini, Matheus Cavalheiro / Bispos-Dos-Santos, Karina / Simeoni, Camila L / Granja, Fabiana / Silvestrini, Virgínia C / de Oliveira, Eduardo B / Faca, Vitor M / Carvalho, Murilo / Castelucci, Bianca G / Pereira, Alexandre B / Coimbra, Laís D / Dias, Marieli M G / Rodrigues, Patricia B / Gomes, Arilson Bernardo S P / Pereira, Fabricio B / Santos, Leonilda M B / Bloyet, Louis-Marie / Stumpf, Spencer / Pontelli, Marjorie C / Whelan, Sean / Sposito, Andrei C / Carvalho, Robson F / Vieira, André S / Vinolo, Marco A R / Damasio, André / Velloso, Licio / Figueira, Ana Carolina M / da Silva, Luis L P / Cunha, Thiago Mattar / Nakaya, Helder I / Marques-Souza, Henrique / Marques, Rafael E / Martins-de-Souza, Daniel / Skaf, Munir S / Proenca-Modena, Jose Luiz / Moraes-Vieira, Pedro M M / Mori, Marcelo A / Farias, Alessandro S

eLife

2023 Volume 12

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; CD8-Positive T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Lung
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.84790
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Article ; Online: Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.

Codo, Ana Campos / Davanzo, Gustavo Gastão / Monteiro, Lauar de Brito / de Souza, Gabriela Fabiano / Muraro, Stéfanie Primon / Virgilio-da-Silva, João Victor / Prodonoff, Juliana Silveira / Carregari, Victor Corasolla / de Biagi Junior, Carlos Alberto Oliveira / Crunfli, Fernanda / Jimenez Restrepo, Jeffersson Leandro / Vendramini, Pedro Henrique / Reis-de-Oliveira, Guilherme / Bispo Dos Santos, Karina / Toledo-Teixeira, Daniel A / Parise, Pierina Lorencini / Martini, Matheus Cavalheiro / Marques, Rafael Elias / Carmo, Helison R /

Borin, Alexandre / Coimbra, Laís Durço / Boldrini, Vinícius O / Brunetti, Natalia S / Vieira, Andre S / Mansour, Eli / Ulaf, Raisa G / Bernardes, Ana F / Nunes, Thyago A / Ribeiro, Luciana C / Palma, Andre C / Agrela, Marcus V / Moretti, Maria Luiza / Sposito, Andrei C / Pereira, Fabrício Bíscaro / Velloso, Licio Augusto / Vinolo, Marco Aurélio Ramirez / Damasio, André / Proença-Módena, José Luiz / Carvalho, Robson Francisco / Mori, Marcelo A / Martins-de-Souza, Daniel / Nakaya, Helder I / Farias, Alessandro S / Moraes-Vieira, Pedro M

Cell metabolism

2020 Volume 32, Issue 3, Page(s) 437–446.e5

Abstract: COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what ... ...

Abstract	COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
MeSH term(s)	Adult ; Betacoronavirus/physiology ; Blood Glucose/metabolism ; COVID-19 ; Cell Line ; Coronavirus Infections/complications ; Coronavirus Infections/metabolism ; Diabetes Complications/complications ; Diabetes Complications/metabolism ; Diabetes Mellitus/metabolism ; Female ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammation/complications ; Inflammation/metabolism ; Male ; Middle Aged ; Monocytes/metabolism ; Monocytes/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/metabolism ; Reactive Oxygen Species/metabolism ; SARS-CoV-2 ; Signal Transduction
Chemical Substances	Blood Glucose ; HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; Reactive Oxygen Species
Keywords	covid19
Language	English
Publishing date	2020-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2020.07.007
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Article ; Online: Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.

Cell metabolism

2020 Volume 32, Issue 3, Page(s) 498–499

Keywords	covid19
Language	English
Publishing date	2020-08-30
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2020.07.015
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Article ; Online: Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.

Souza, William M / Amorim, Mariene R / Sesti-Costa, Renata / Coimbra, Lais D / Brunetti, Natalia S / Toledo-Teixeira, Daniel A / de Souza, Gabriela F / Muraro, Stefanie P / Parise, Pierina L / Barbosa, Priscilla P / Bispo-Dos-Santos, Karina / Mofatto, Luciana S / Simeoni, Camila L / Claro, Ingra M / Duarte, Adriana S S / Coletti, Thais M / Zangirolami, Audrey B / Costa-Lima, Carolina / Gomes, Arilson B S P /

Buscaratti, Lucas I / Sales, Flavia C / Costa, Vitor A / Franco, Lucas A M / Candido, Darlan S / Pybus, Oliver G / de Jesus, Jaqueline G / Silva, Camila A M / Ramundo, Mariana S / Ferreira, Giulia M / Pinho, Mariana C / Souza, Leandro M / Rocha, Esmenia C / Andrade, Pamela S / Crispim, Myuki A E / Maktura, Grazielle C / Manuli, Erika R / Santos, Magnun N N / Camilo, Cecilia C / Angerami, Rodrigo N / Moretti, Maria L / Spilki, Fernando R / Arns, Clarice W / Addas-Carvalho, Marcelo / Benites, Bruno D / Vinolo, Marco A R / Mori, Marcelo A S / Gaburo, Nelson / Dye, Christopher / Marques-Souza, Henrique / Marques, Rafael E / Farias, Alessandro S / Diamond, Michael S / Faria, Nuno R / Sabino, Ester C / Granja, Fabiana / Proença-Módena, Jose Luiz

The Lancet. Microbe

2021 Volume 2, Issue 10, Page(s) e527–e535

Abstract: Background: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B. ...

Abstract	Background: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. Methods: We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17-38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134-230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT Findings: In terms of VNT Interpretation: SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. Funding: São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. Translation: For the Portuguese translation of the abstract see Supplementary Materials section.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; Brazil/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2/genetics ; United States ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2021-07-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-5247
ISSN (online)	2666-5247
DOI	10.1016/S2666-5247(21)00129-4
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Article: Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis

Cell Metab

Abstract	COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1É may have great therapeutic potential for the development of novel drugs to treat COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #670096
Database	COVID19

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