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Article ; Online: Detection of SARS-CoV-2 in placental but not fetal tissues in the second trimester.

Valk, Jacob E / Chong, Alexander M / Uhlemann, Anne-Catrin / Debelenko, Larisa

Journal of perinatology : official journal of the California Perinatal Association

2020 Volume 41, Issue 5, Page(s) 1184–1186

MeSH term(s)	Adolescent ; Adult ; COVID-19/diagnosis ; Female ; Humans ; Infant, Newborn ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/virology ; Pregnancy Trimester, Second ; SARS-CoV-2/isolation & purification ; Stillbirth
Language	English
Publishing date	2020-11-30
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	645021-0
ISSN	1476-5543 ; 0743-8346
ISSN (online)	1476-5543
ISSN	0743-8346
DOI	10.1038/s41372-020-00877-8
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Zs.A 2412: Show issues

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Article ; Online: Trophoblast damage with acute and chronic intervillositis: disruption of the placental barrier by severe acute respiratory syndrome coronavirus 2.

Debelenko, Larisa / Katsyv, Igor / Chong, Alexander M / Peruyero, Leonore / Szabolcs, Matthias / Uhlemann, Anne-Catrin

Human pathology

2020 Volume 109, Page(s) 69–79

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was demonstrated in the placenta; however, the data on the prevalence of placental infection and associated histopathology are limited. To identify the frequency and features of SARS-CoV-2 ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was demonstrated in the placenta; however, the data on the prevalence of placental infection and associated histopathology are limited. To identify the frequency and features of SARS-CoV-2 involvement, we performed a clinicopathologic analysis of 75 placental cases from women infected at the time of delivery and 75 uninfected controls. Placental samples were studied with anti-SARS-CoV-2 immunohistochemistry and/or in situ hybridization. Positive results were confirmed by electron microscopy and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). During delivery, only one woman had symptoms of coronavirus disease 2019, six women reported previous symptoms, and 68 women were asymptomatic. All neonates tested negative for SARS-CoV-2 as per nasopharyngeal swab PCR results. Obstetric histories were unremarkable in 29 of 75 SARS-CoV-2-positive and 8 of 75 SARS-CoV-2-negative women. Placental examination was normal in 12 of 75 infected and 3 of 75 uninfected subjects, respectively. In the remaining cases, placental pathology correlated with obstetric comorbidities without significant differences between SARS-CoV-2-positive and SARS-CoV-2-negative women. SARS-CoV-2 was identified in one placenta of an infected, but asymptomatic, parturient. Viral staining was predominantly localized to the syncytiotrophoblast (STB) which demonstrated marked damage accompanied by perivillous fibrin deposition and mixed intervillositis. A significant decrease of viral titers was detected in the attached umbilical cord compared with the villous parenchyma as per qRT-PCR. SARS-CoV-2 is seldom identified in placentas of infected women. Placental involvement by the virus is characterized by STB damage disrupting the placental barrier and can be seen in asymptomatic mothers without evidence of vertical transmission.
MeSH term(s)	Adult ; COVID-19/virology ; Female ; Humans ; In Situ Hybridization/methods ; Placenta/pathology ; Placenta/virology ; Pregnancy ; RNA, Viral ; SARS-CoV-2/pathogenicity ; Trophoblasts/chemistry ; Trophoblasts/pathology ; Trophoblasts/virology ; Viral Load
Chemical Substances	RNA, Viral
Language	English
Publishing date	2020-12-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2020.12.004
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Zs.A 722: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Intrathymic differentiation of natural antibody-producing plasma cells in human neonates.

Cordero, Hector / King, Rodney G / Dogra, Pranay / Dufeu, Chloe / See, Sarah B / Chong, Alexander M / Uhlemann, Anne-Catrin / Ho, Siu-Hong / Kalfa, David M / Bacha, Emile A / Kearney, John F / Zorn, Emmanuel

Nature communications

2021 Volume 12, Issue 1, Page(s) 5761

Abstract: The thymus is a central lymphoid organ primarily responsible for the development of T cells. A small proportion of B cells, however, also reside in the thymus to assist negative selection of self-reactive T cells. Here we show that the thymus of human ... ...

Abstract	The thymus is a central lymphoid organ primarily responsible for the development of T cells. A small proportion of B cells, however, also reside in the thymus to assist negative selection of self-reactive T cells. Here we show that the thymus of human neonates contains a consistent contingent of CD138
MeSH term(s)	Adult ; Antigens, CD/metabolism ; B-Lymphocytes/cytology ; B-Lymphocytes/metabolism ; B-Lymphocytes/ultrastructure ; Cell Differentiation ; Fetal Blood/cytology ; Gene Expression Profiling ; Humans ; Immunity, Innate ; Immunoglobulin G/metabolism ; Immunoglobulin Heavy Chains/immunology ; Immunoglobulin Variable Region/immunology ; Infant, Newborn ; Lymphocyte Subsets/cytology ; Plasma Cells/cytology ; Principal Component Analysis ; RNA-Seq ; Single-Cell Analysis ; Somatic Hypermutation, Immunoglobulin/genetics ; Thymus Gland/cytology ; Transcriptome/genetics
Chemical Substances	Antigens, CD ; Immunoglobulin G ; Immunoglobulin Heavy Chains ; Immunoglobulin Variable Region
Language	English
Publishing date	2021-10-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-26069-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 RNA Shedding in Semen and Oligozoospermia of Patient with Severe Coronavirus Disease 11 Weeks after Infection.

Purpura, Lawrence J / Alukal, Joseph / Chong, Alexander M / Liu, Lihong / Cantos, Anyelina / Shah, Jayesh / Medrano, Nicola / Chang, Jennifer Y / Tsuji, Moriya / Mohri, Hiroshi / Uhlemann, Anne Catrin / Ho, David / Yin, Michael T

Emerging infectious diseases

2021 Volume 28, Issue 1, Page(s) 196–200

Abstract: We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of ... ...

Abstract	We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.
MeSH term(s)	COVID-19 ; Humans ; Male ; Oligospermia ; RNA, Viral/genetics ; SARS-CoV-2 ; Semen ; Semen Analysis ; Virus Shedding
Chemical Substances	RNA, Viral
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2801.211521
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Article ; Online: Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

Miller, Emily Happy / Annavajhala, Medini K / Chong, Alexander M / Park, Heekuk / Nobel, Yael R / Soroush, Ali / Blackett, John W / Krigel, Anna / Phipps, Meaghan M / Freedberg, Daniel E / Zucker, Jason / Sano, Ellen D / Uhlemann, Anne-Catrin / Abrams, Julian A

Microbiology spectrum

2021 Volume 9, Issue 2, Page(s) e0005521

Abstract: Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to ...

Abstract	Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (
MeSH term(s)	Bacteria/classification ; Bacteria/genetics ; COVID-19/pathology ; Dysbiosis/microbiology ; Female ; Humans ; Male ; Microbial Interactions/physiology ; Microbiota/genetics ; Middle Aged ; Nasopharynx/microbiology ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2/isolation & purification ; Saliva/microbiology ; Viral Load
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/Spectrum.00055-21
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Article ; Online: An acquired acyltransferase promotes Klebsiella pneumoniae ST258 respiratory infection.

Ahn, Danielle / Bhushan, Gitanjali / McConville, Thomas H / Annavajhala, Medini K / Soni, Rajesh Kumar / Wong Fok Lung, Tania / Hofstaedter, Casey E / Shah, Shivang S / Chong, Alexander M / Castano, Victor G / Ernst, Robert K / Uhlemann, Anne-Catrin / Prince, Alice

Cell reports

2021 Volume 35, Issue 9, Page(s) 109196

Abstract: Klebsiella pneumoniae ST258 is a human pathogen associated with poor outcomes worldwide. We identify a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation ... ...

Abstract	Klebsiella pneumoniae ST258 is a human pathogen associated with poor outcomes worldwide. We identify a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of these organisms in vivo. Comparison of a wild-type ST258 strain (KP35) and a Δatf3 isogenic mutant generated by CRISPR-Cas9 targeting reveals greater NADH:ubiquinone oxidoreductase transcription and ATP generation, fueled by increased glycolysis. The acquisition of atf3 induces changes in the bacterial acetylome, promoting lysine acetylation of multiple proteins involved in central metabolism, specifically Zwf (glucose-6 phosphate dehydrogenase). The atf3-mediated metabolic boost leads to greater consumption of glucose in the host airway and increased bacterial burden in the lung, independent of cytokine levels and immune cell recruitment. Acquisition of this acyltransferase enhances fitness of a K. pneumoniae ST258 isolate and may contribute to the success of this clonal complex as a healthcare-associated pathogen.
MeSH term(s)	Acetylation ; Acyltransferases/metabolism ; Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carbapenems/pharmacology ; Citric Acid Cycle ; Gene Deletion ; Glucose/metabolism ; Glycolysis/drug effects ; Klebsiella Infections/enzymology ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/enzymology ; Klebsiella pneumoniae/growth & development ; Klebsiella pneumoniae/isolation & purification ; Klebsiella pneumoniae/physiology ; Lipid A/metabolism ; Lung/drug effects ; Lung/microbiology ; Lung/pathology ; Lysine/metabolism ; Male ; Metabolome/drug effects ; Metabolomics ; Mice, Inbred C57BL ; Phylogeny ; Protein Processing, Post-Translational/drug effects ; Respiratory Tract Infections/enzymology ; Respiratory Tract Infections/microbiology ; Mice
Chemical Substances	Bacterial Proteins ; Carbapenems ; Lipid A ; Acyltransferases (EC 2.3.-) ; Glucose (IY9XDZ35W2) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109196
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Article: Cerebrospinal Analysis in Patients With COVID-19.

Miller, Emily Happy / Namale, Vivian S / Kim, Carla / Dugue, Rachelle / Waldrop, Greer / Ciryam, Prajwal / Chong, Alexander M / Zucker, Jason / Miller, Eliza C / Bain, Jennifer M / Willey, Joshua Z / Doyle, Kevin / Boehme, Amelia / Claassen, Jan / Uhlemann, Anne-Catrin / Thakur, Kiran T

Open forum infectious diseases

2020 Volume 7, Issue 11, Page(s) ofaa501

Abstract: Background: Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care.: Methods: In this ... ...

Abstract	Background: Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care. Methods: In this case series, we review patients diagnosed with SARS-CoV-2 undergoing lumbar puncture (LP) admitted to Columbia University Irving Medical Center (New York, NY, USA) from March 1 to May 26, 2020. In a subset of patients, CSF SARS-CoV-2 quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) testing is performed. Results: The average age of 27 patients who underwent LP with definitive SARS-CoV-2 (SD) was 37.5 (28.7) years. CSF profiles showed elevated white blood cell counts and protein in 44% and 52% of patients, respectively. LP results impacted treatment decisions in 10 (37%) patients, either by change of antibiotics, influence in disposition decision, or by providing an alternative diagnosis. CSF SARS-CoV-2 qRT-PCR was performed on 8 (30%) patients, with negative results in all samples. Conclusions: Among patients diagnosed with SARS-CoV-2, CSF results changed treatment decisions or disposition in over one-third of our patient cohort. CSF was frequently abnormal, though CSF SARS-CoV-2 qRT-PCR was negative in all samples. Further studies are required to define whether CSF SARS-CoV-2 testing is warranted in certain clinical contexts.
Language	English
Publishing date	2020-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofaa501
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Article ; Online: Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data.

Lagana, Stephen M / Kudose, Satoru / Iuga, Alina C / Lee, Michael J / Fazlollahi, Ladan / Remotti, Helen E / Del Portillo, Armando / De Michele, Simona / de Gonzalez, Anne Koehne / Saqi, Anjali / Khairallah, Pascale / Chong, Alexander M / Park, Heekuk / Uhlemann, Anne-Catrin / Lefkowitch, Jay H / Verna, Elizabeth C

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2020 Volume 33, Issue 11, Page(s) 2147–2155

Abstract: The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic evaluation. The histologic pattern of injury has not been ... ...

Abstract	The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic evaluation. The histologic pattern of injury has not been completely described. Studies quantifying viral load in the liver are lacking. Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. A subset of liver tissue blocks were subjected to polymerase chain reaction (PCR) for viral ribonucleic acid (RNA). Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated; median ALT peak 68 U/l (normal up to 46 U/l) and median AST peak 102 U/l (normal up to 37 U/l). Macrovesicular steatosis was the most common finding, involving 30 patients (75%). Mild lobular necroinflammation and portal inflammation were present in 20 cases each (50%). Vascular pathology, including sinusoidal microthrombi, was infrequent, seen in six cases (15%). PCR of liver tissue was positive in 11 of 20 patients tested (55%). In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. We also identified viral RNA in a sizeable subset of liver tissue samples.
MeSH term(s)	Aged ; Aged, 80 and over ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Female ; Humans ; Liver Diseases/pathology ; Liver Diseases/virology ; Male ; Pandemics ; Pneumonia, Viral/complications ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-08-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1038/s41379-020-00649-x
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Zs.A 2450: Show issues

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Article: Cerebrospinal Fluid (CSF) Analysis in Patients with COVID-19

Miller, Emily Happy / Namale, Vivian S. / Kim, Carla / Dugue, Rachelle / Waldrop, Greer / Ciryam, Prajwal / Chong, Alexander M. / Zucker, Jason / Miller, Eliza C. / Bain, Jennifer M. / Willey, Joshua Z. / Doyle, Kevin / Boehme, Amelia / Claassen, Jan / Uhlemann, Anne-Catrin / Thakur, Kiran T.

Open Forum Infectious Diseases

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #873055
Database	COVID19

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Article: Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data

Mod Pathol

Abstract	The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic evaluation. The histologic pattern of injury has not been completely described. Studies quantifying viral load in the liver are lacking. Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. A subset of liver tissue blocks were subjected to polymerase chain reaction (PCR) for viral ribonucleic acid (RNA). Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated; median ALT peak 68 U/l (normal up to 46 U/l) and median AST peak 102 U/l (normal up to 37 U/l). Macrovesicular steatosis was the most common finding, involving 30 patients (75%). Mild lobular necroinflammation and portal inflammation were present in 20 cases each (50%). Vascular pathology, including sinusoidal microthrombi, was infrequent, seen in six cases (15%). PCR of liver tissue was positive in 11 of 20 patients tested (55%). In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. We also identified viral RNA in a sizeable subset of liver tissue samples.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #720825
Database	COVID19

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