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Article ; Online: Risk factors for severe COVID-19 illness in healthcare workers: Too many unknowns.

Wander, Pandora L / Orlov, Marika / Merel, Susan E / Enquobahrie, Daniel A

Infection control and hospital epidemiology

2020 Volume 41, Issue 11, Page(s) 1369–1370

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus ; Coronavirus Infections/epidemiology ; Health Personnel ; Humans ; Pandemics ; Pneumonia, Viral ; Risk Factors ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-04-27
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2020.178
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Endotracheal aspirates contain a limited number of lower respiratory tract immune cells.

Orlov, Marika / Morrell, Eric D / Dmyterko, Victoria / Hamerman, Jessica A / Wurfel, Mark M / Mikacenic, Carmen

Critical care (London, England)

2021 Volume 25, Issue 1, Page(s) 14

MeSH term(s)	Adult ; Aged ; B-Lymphocytes/cytology ; Body Fluids/cytology ; Female ; Humans ; Lymphocytes/cytology ; Macrophages, Alveolar/cytology ; Male ; Middle Aged ; Monocytes/cytology ; Paracentesis/methods ; Respiratory System/cytology ; Respiratory System/physiopathology ; T-Lymphocytes/cytology
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Letter
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-020-03432-1
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Article: Risk factors for severe COVID-19 illness in healthcare workers: Too many unknowns

Wander, Pandora L / Orlov, Marika / Merel, Susan E / Enquobahrie, Daniel A

Infect Control Hosp Epidemiol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32336303
Database	COVID19

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Article ; Online: Risk factors for severe COVID-19 illness in healthcare workers

Wander, Pandora L. / Orlov, Marika / Merel, Susan E. / Enquobahrie, Daniel A.

Infection Control & Hospital Epidemiology

Too many unknowns

2020 Volume 41, Issue 11, Page(s) 1369–1370

Keywords	Microbiology (medical) ; Epidemiology ; Infectious Diseases ; covid19
Language	English
Publisher	Cambridge University Press (CUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2020.178
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Case for Targeting Th17 Cells and IL-17A in SARS-CoV-2 Infections.

Orlov, Marika / Wander, Pandora L / Morrell, Eric D / Mikacenic, Carmen / Wurfel, Mark M

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 205, Issue 4, Page(s) 892–898

Abstract: SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying ... ...

Abstract	SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.
MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Betacoronavirus/immunology ; COVID-19 ; Comorbidity ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Critical Illness ; Female ; Humans ; Interleukin-17/antagonists & inhibitors ; Interleukin-17/metabolism ; Male ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/virology ; Respiratory Distress Syndrome/immunology ; Respiratory Distress Syndrome/mortality ; Respiratory Distress Syndrome/virology ; Risk Factors ; SARS-CoV-2 ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Th17 Cells/drug effects ; Th17 Cells/immunology
Chemical Substances	Antibodies, Monoclonal, Humanized ; IL17A protein, human ; Interleukin-17
Keywords	covid19
Language	English
Publishing date	2020-07-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2000554
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure.

Morrell, Eric D / Holton, Sarah E / Lawrance, Matthew / Orlov, Marika / Franklin, Zoie / Mitchem, Mallorie A / DeBerg, Hannah / Gersuk, Vivian H / Garay, Ashley / Barnes, Elizabeth / Liu, Ted / Peltan, Ithan D / Rogers, Angela / Ziegler, Steven / Wurfel, Mark M / Mikacenic, Carmen

Nature communications

2023 Volume 14, Issue 1, Page(s) 7443

Abstract: The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein ... ...

Abstract	The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein quantification) to bronchoalveolar lavage and blood specimens longitudinally collected from participants with AHRF to identify alveolar myeloid subsets, and then validate their identity in an external cohort using flow cytometry. We identify alveolar myeloid subsets with transcriptional profiles that differ from other lung diseases as well as several subsets with similar transcriptional profiles as reported in healthy participants (Metallothionein) or patients with COVID-19 (CD163/LGMN). We use information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86 and CD44). In the external cohort, we find a higher proportion of CD163/LGMN alveolar macrophages are associated with mortality in AHRF. We report a parsimonious set of cell-surface proteins that distinguish alveolar myeloid subsets using scalable approaches that can be applied to clinical cohorts.
MeSH term(s)	Humans ; Macrophages, Alveolar/metabolism ; Macrophages/metabolism ; Monocytes/metabolism ; Lung Diseases/metabolism ; Respiratory Insufficiency/genetics
Language	English
Publishing date	2023-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43223-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Th17 cells are associated with protection from ventilator associated pneumonia.

Orlov, Marika / Dmyterko, Victoria / Wurfel, Mark M / Mikacenic, Carmen

PloS one

2017 Volume 12, Issue 8, Page(s) e0182966

Abstract: Background: CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial ... ...

Abstract	Background: CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial pneumonia in humans. Methods: We collected bronchoalveolar lavage (BAL) fluid from mechanically ventilated (n = 25) patients undergoing quantitative bacterial culture to evaluate for ventilator associated pneumonia (VAP). We identified Th17 cells by positive selection of CD4+ cells, stimulation with ionomycin and PMA, then staining for CD4, CD45, CCR6, IL-17A, and IFN-γ followed by flow cytometric analysis (n = 21). We measured inflammatory cytokine levels, including IL-17A, in BAL fluid by immunoassay. Results: VAP was detected in 13 of the 25 subjects. We identified a decreased percentage of IL-17A producing Th17 cells in BAL fluid from patients with VAP compared to those without (p = 0.02). However, we found no significant difference in levels of IL-17A in patients with VAP compared to those without (p = 0.07). Interestingly, IL-17A levels did not correlate with Th17 cell numbers. IL-17A levels did show strong positive correlations with alveolar neutrophil numbers and total protein levels. Conclusions: Th17 cells are found at lower percentages in BAL fluid from mechanically ventilated patients with VAP and IL-17A levels correlated with Th17 cell percentages in non-VAP subjects, but not those with VAP. These findings suggest that Th17 cells may be protective against development of nosocomial pneumonia in patients receiving mechanical ventilation and that alveolar IL-17A in VAP may be derived from sources other than alveolar Th17 cells.
MeSH term(s)	Bronchoalveolar Lavage Fluid ; Demography ; Female ; Flow Cytometry ; Humans ; Inflammation Mediators/metabolism ; Interleukin-17/metabolism ; Male ; Middle Aged ; Neutrophil Infiltration ; Pneumonia, Ventilator-Associated/immunology ; Pneumonia, Ventilator-Associated/prevention & control ; Th17 Cells/immunology
Chemical Substances	IL17A protein, human ; Inflammation Mediators ; Interleukin-17
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0182966
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Th17 cells are associated with protection from ventilator associated pneumonia.

Marika Orlov / Victoria Dmyterko / Mark M Wurfel / Carmen Mikacenic

PLoS ONE, Vol 12, Iss 8, p e

2017 Volume 0182966

Abstract: CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial pneumonia in humans ... ...

Abstract	CD4+ T-helper 17 (Th17) cells and Interleukin (IL)-17A play an important role in clearing pathogens in mouse models of pneumonia. We hypothesized that numbers of Th17 cells and levels of IL-17A are associated with risk for nosocomial pneumonia in humans.We collected bronchoalveolar lavage (BAL) fluid from mechanically ventilated (n = 25) patients undergoing quantitative bacterial culture to evaluate for ventilator associated pneumonia (VAP). We identified Th17 cells by positive selection of CD4+ cells, stimulation with ionomycin and PMA, then staining for CD4, CD45, CCR6, IL-17A, and IFN-γ followed by flow cytometric analysis (n = 21). We measured inflammatory cytokine levels, including IL-17A, in BAL fluid by immunoassay.VAP was detected in 13 of the 25 subjects. We identified a decreased percentage of IL-17A producing Th17 cells in BAL fluid from patients with VAP compared to those without (p = 0.02). However, we found no significant difference in levels of IL-17A in patients with VAP compared to those without (p = 0.07). Interestingly, IL-17A levels did not correlate with Th17 cell numbers. IL-17A levels did show strong positive correlations with alveolar neutrophil numbers and total protein levels.Th17 cells are found at lower percentages in BAL fluid from mechanically ventilated patients with VAP and IL-17A levels correlated with Th17 cell percentages in non-VAP subjects, but not those with VAP. These findings suggest that Th17 cells may be protective against development of nosocomial pneumonia in patients receiving mechanical ventilation and that alveolar IL-17A in VAP may be derived from sources other than alveolar Th17 cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A Case for Targeting Th17 Cells and IL-17A in SARS-CoV-2 Infections

Orlov, Marika / Wander, Pandora L / Morrell, Eric D / Mikacenic, Carmen / Wurfel, Mark M

J Immunol

Abstract	SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #638521
Database	COVID19

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Article ; Online: Presence of Plasmodium falciparum DNA in Plasma Does Not Predict Clinical Malaria in an HIV-1 Infected Population.

Orlov, Marika / Smeaton, Laura M / Kumwenda, Johnstone / Hosseinipour, Mina C / Campbell, Thomas B / Schooley, Robert T

PloS one

2015 Volume 10, Issue 6, Page(s) e0129519

Abstract: Background: HIV-1 and Plasmodium falciparum malaria cause substantial morbidity in Sub-Saharan Africa, especially as co-infecting pathogens. We examined the relationship between presence of P. falciparum DNA in plasma samples and clinical malaria as ... ...

Abstract	Background: HIV-1 and Plasmodium falciparum malaria cause substantial morbidity in Sub-Saharan Africa, especially as co-infecting pathogens. We examined the relationship between presence of P. falciparum DNA in plasma samples and clinical malaria as well as the impact of atazanavir, an HIV-1 protease inhibitor (PI), on P. falciparum PCR positivity. Methods: ACTG study A5175 compared two NNRTI-based regimens and one PI-based anti-retroviral (ARV) regimen in antiretroviral therapy naïve participants. We performed nested PCR on plasma samples for the P. falciparum 18s rRNA gene to detect the presence of malaria DNA in 215 of the 221 participants enrolled in Blantyre and Lilongwe, Malawi. We also studied the closest sample preceding the first malaria diagnosis from 102 persons with clinical malaria and randomly selected follow up samples from 88 persons without clinical malaria. Results: PCR positivity was observed in 18 (8%) baseline samples and was not significantly associated with age, sex, screening CD4+ T-cell count, baseline HIV-1 RNA level or co-trimoxazole use within the first 8 weeks. Neither baseline PCR positivity (p = 0.45) nor PCR positivity after initiation of antiretroviral therapy (p = 1.0) were significantly associated with subsequent clinical malaria. Randomization to the PI versus NNRTI ARV regimens was not significantly associated with either PCR positivity (p = 0.5) or clinical malaria (p = 0.609). Clinical malaria was associated with a history of tuberculosis (p = 0.006) and a lower BMI (p = 0.004). Conclusion: P. falciparum DNA was detected in 8% of participants at baseline, but was not significantly associated with subsequent development of clinical malaria. HIV PI therapy did not decrease the prevalence of PCR positivity or incidence of clinical disease.
MeSH term(s)	Adolescent ; Adult ; Aged ; DNA, Protozoan/blood ; Female ; HIV Infections/blood ; HIV Infections/complications ; HIV Infections/parasitology ; HIV Infections/virology ; HIV-1/physiology ; Humans ; Malaria/blood ; Malaria/complications ; Malaria/parasitology ; Malaria/virology ; Male ; Middle Aged ; Parasitemia/blood ; Parasitemia/epidemiology ; Parasitemia/parasitology ; Plasmodium falciparum/metabolism ; Prevalence ; Young Adult
Chemical Substances	DNA, Protozoan
Language	English
Publishing date	2015-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0129519
Database	MEDical Literature Analysis and Retrieval System OnLINE

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