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Article ; Online: Risk of Strongyloides Hyperinfection Syndrome when prescribing dexamethasone in severe COVID-19.

De Wilton, Angus / Nabarro, Laura E / Godbole, Gauri S / Chiodini, Peter L / Boyd, Aileen / Woods, Katherine

2021 Volume 40, Page(s) 101981

MeSH term(s)	Animals ; COVID-19/drug therapy ; Dexamethasone/adverse effects ; Humans ; SARS-CoV-2 ; Steroids ; Strongyloides stercoralis ; Strongyloidiasis/drug therapy
Chemical Substances	Steroids ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2021-01-31
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	2170891-5
ISSN	1873-0442 ; 1477-8939
ISSN (online)	1873-0442
ISSN	1477-8939
DOI	10.1016/j.tmaid.2021.101981
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Article ; Online: Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country: A tertiary referral centre experience.

de Wilton, Angus / Aggarwal, Dinesh / Jäger, Hans Rolf / Manji, Hadi / Chiodini, Peter L

PLoS neglected tropical diseases

2021 Volume 15, Issue 2, Page(s) e0009161

Abstract: Background: Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids ... ...

Abstract	Background: Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre. Materials/methods: A retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected. Results: Four cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16-74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation. Conclusion: We observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis.
MeSH term(s)	Adult ; Delayed Diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Malawi ; Male ; Middle Aged ; Myelitis, Transverse ; Neuroschistosomiasis/diagnosis ; Nigeria ; Praziquantel/therapeutic use ; Retrospective Studies ; Risk Factors ; Schistosomiasis/diagnostic imaging ; Schistosomiasis/drug therapy ; Schistosomiasis/pathology ; Spinal Cord/parasitology ; Spinal Cord Diseases/diagnosis ; Spinal Cord Diseases/parasitology ; Tertiary Care Centers ; Uganda ; United Kingdom ; Young Adult
Chemical Substances	Praziquantel (6490C9U457)
Language	English
Publishing date	2021-02-11
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0009161
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country

Angus de Wilton / Dinesh Aggarwal / Hans Rolf Jäger / Hadi Manji / Peter L Chiodini

PLoS Neglected Tropical Diseases, Vol 15, Iss 2, p e

A tertiary referral centre experience.

2021 Volume 0009161

Abstract: Background Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids ... ...

Abstract	Background Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre. Materials/methods A retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected. Results Four cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16-74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation. Conclusion We observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic: a single-centre observational study.

de Wilton, Angus / Kilich, Eliz / Chaudhry, Zain / Bell, Lucy Ck / Gahir, Joshua / Cadman, Jane / Lever, Robert A / Logan, Sarah A

BMJ open

2020 Volume 10, Issue 11, Page(s) e040216

Abstract: Objectives: To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.: Design: A cross-sectional, single-centre study.: Setting: A large, teaching hospital based in Central London with tertiary infection services.: ...

Abstract	Objectives: To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men. Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19.
MeSH term(s)	Adolescent ; Adult ; Aged ; COVID-19/epidemiology ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Health Behavior ; Health Facilities/statistics & numerical data ; Health Personnel/psychology ; Humans ; Male ; Middle Aged ; Pandemics ; SARS-CoV-2 ; Time Factors ; United Kingdom/epidemiology ; Young Adult
Language	English
Publishing date	2020-11-26
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2020-040216
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Article ; Online: Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic

Sarah A Logan / Zain Chaudhry / Angus de Wilton / Eliz Kilich / Lucy CK Bell / Joshua Gahir / Jane Cadman / Robert A Lever

BMJ Open, Vol 10, Iss

a single-centre observational study

2020 Volume 11

Abstract: Objectives To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.Design A cross-sectional, single-centre study.Setting A large, teaching hospital based in Central London with tertiary infection services.Participants 236 ... ...

Abstract	Objectives To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.Design A cross-sectional, single-centre study.Setting A large, teaching hospital based in Central London with tertiary infection services.Participants 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men.Measures Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report.Results The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off.Conclusion There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19.
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical and behavioural characteristics of self-isolating healthcare workers during the COVID-19 pandemic: a single-centre observational study

de Wilton, Angus / Kilich, Eliz / Chaudhry, Zain / Bell, Lucy CK / Gahir, Joshua / Cadman, Jane / Lever, Robert A / Logan, Sarah

medRxiv

Abstract: Objectives:To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: ...

Abstract	Objectives:To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were female and 65 male. Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020. Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Conclusions cannot be drawn about exact numbers of confirmed cases due to lack of diagnostic swabbing. There were significant numbers of respondents reporting anosmia; as well as early non-specific illness prior to onset of cough and fever. This may represent pre-symptomatic HCWs who are likely to be infectious and thus criteria for isolation and swabbing should be broadened. The study also revealed concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This should be addressed urgently to reduce risk of severe disease being detected late. Finally, this study should inform trusts that HCWs may require longer than 7 days off work to recover from illness.
Keywords	covid19
Language	English
Publishing date	2020-05-11
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.05.07.20094177
Database	COVID19

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Article ; Online: Clinical and behavioural characteristics of self-isolating healthcare workers during the COVID-19 pandemic: a single-centre observational study

Wilton, Angus de / Kilich, Eliz / Chaudhry, Zain / Bell, Lucy CK / Gahir, Joshua / Cadman, Jane / Lever, Robert A / Logan, Sarah

Abstract	Objectives:To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were female and 65 male. Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020. Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Conclusions cannot be drawn about exact numbers of confirmed cases due to lack of diagnostic swabbing. There were significant numbers of respondents reporting anosmia; as well as early non-specific illness prior to onset of cough and fever. This may represent pre-symptomatic HCWs who are likely to be infectious and thus criteria for isolation and swabbing should be broadened. The study also revealed concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This should be addressed urgently to reduce risk of severe disease being detected late. Finally, this study should inform trusts that HCWs may require longer than 7 days off work to recover from illness.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
Note	WHO #Covidence: #20094177
DOI	10.1101/2020.05.07.20094177
Database	COVID19

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Article ; Online: Local and systemic responses to SARS-CoV-2 infection in children and adults.

Yoshida, Masahiro / Worlock, Kaylee B / Huang, Ni / Lindeboom, Rik G H / Butler, Colin R / Kumasaka, Natsuhiko / Dominguez Conde, Cecilia / Mamanova, Lira / Bolt, Liam / Richardson, Laura / Polanski, Krzysztof / Madissoon, Elo / Barnes, Josephine L / Allen-Hyttinen, Jessica / Kilich, Eliz / Jones, Brendan C / de Wilton, Angus / Wilbrey-Clark, Anna / Sungnak, Waradon /

Pett, J Patrick / Weller, Juliane / Prigmore, Elena / Yung, Henry / Mehta, Puja / Saleh, Aarash / Saigal, Anita / Chu, Vivian / Cohen, Jonathan M / Cane, Clare / Iordanidou, Aikaterini / Shibuya, Soichi / Reuschl, Ann-Kathrin / Herczeg, Iván T / Argento, A Christine / Wunderink, Richard G / Smith, Sean B / Poor, Taylor A / Gao, Catherine A / Dematte, Jane E / Reynolds, Gary / Haniffa, Muzlifah / Bowyer, Georgina S / Coates, Matthew / Clatworthy, Menna R / Calero-Nieto, Fernando J / Göttgens, Berthold / O'Callaghan, Christopher / Sebire, Neil J / Jolly, Clare / De Coppi, Paolo / Smith, Claire M / Misharin, Alexander V / Janes, Sam M / Teichmann, Sarah A / Nikolić, Marko Z / Meyer, Kerstin B

Nature

2021 Volume 602, Issue 7896, Page(s) 321–327

Abstract: It is not fully understood why COVID-19 is typically milder in ... ...

Abstract	It is not fully understood why COVID-19 is typically milder in children
MeSH term(s)	Adult ; Bronchi/immunology ; Bronchi/virology ; COVID-19/blood ; COVID-19/immunology ; COVID-19/pathology ; Chicago ; Cohort Studies ; Dendritic Cells/immunology ; Disease Progression ; Epithelial Cells/cytology ; Epithelial Cells/immunology ; Epithelial Cells/virology ; Female ; Humans ; Immunity, Innate ; Interferons/immunology ; Killer Cells, Natural/immunology ; London ; Male ; Nasal Mucosa/immunology ; Nasal Mucosa/virology ; SARS-CoV-2/growth & development ; SARS-CoV-2/immunology ; Single-Cell Analysis ; T-Lymphocytes, Cytotoxic/immunology ; Trachea/virology ; Young Adult
Chemical Substances	Interferons (9008-11-1)
Language	English
Publishing date	2021-12-22
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-04345-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Single-cell multi-omics analysis of the immune response in COVID-19.

Stephenson, Emily / Reynolds, Gary / Botting, Rachel A / Calero-Nieto, Fernando J / Morgan, Michael D / Tuong, Zewen Kelvin / Bach, Karsten / Sungnak, Waradon / Worlock, Kaylee B / Yoshida, Masahiro / Kumasaka, Natsuhiko / Kania, Katarzyna / Engelbert, Justin / Olabi, Bayanne / Spegarova, Jarmila Stremenova / Wilson, Nicola K / Mende, Nicole / Jardine, Laura / Gardner, Louis C S /

Goh, Issac / Horsfall, Dave / McGrath, Jim / Webb, Simone / Mather, Michael W / Lindeboom, Rik G H / Dann, Emma / Huang, Ni / Polanski, Krzysztof / Prigmore, Elena / Gothe, Florian / Scott, Jonathan / Payne, Rebecca P / Baker, Kenneth F / Hanrath, Aidan T / Schim van der Loeff, Ina C D / Barr, Andrew S / Sanchez-Gonzalez, Amada / Bergamaschi, Laura / Mescia, Federica / Barnes, Josephine L / Kilich, Eliz / de Wilton, Angus / Saigal, Anita / Saleh, Aarash / Janes, Sam M / Smith, Claire M / Gopee, Nusayhah / Wilson, Caroline / Coupland, Paul / Coxhead, Jonathan M / Kiselev, Vladimir Yu / van Dongen, Stijn / Bacardit, Jaume / King, Hamish W / Rostron, Anthony J / Simpson, A John / Hambleton, Sophie / Laurenti, Elisa / Lyons, Paul A / Meyer, Kerstin B / Nikolić, Marko Z / Duncan, Christopher J A / Smith, Kenneth G C / Teichmann, Sarah A / Clatworthy, Menna R / Marioni, John C / Göttgens, Berthold / Haniffa, Muzlifah

Nature medicine

2021 Volume 27, Issue 5, Page(s) 904–916

Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, ... ...

Abstract	Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16
MeSH term(s)	COVID-19/immunology ; Cross-Sectional Studies ; Humans ; Monocytes/immunology ; Proteome ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, T-Cell/immunology ; SARS-CoV-2/immunology ; Single-Cell Analysis/methods ; T-Lymphocytes/immunology ; Transcriptome
Chemical Substances	Proteome ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-021-01329-2
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The local and systemic response to SARS-CoV-2 infection in children and adults

Yoshida, Masahiro / Worlock, Kaylee B / Huang, Ni / Lindeboom, Rik GH / Butler, Colin R / Kumasaka, Natsuhiko / Dominguez Conde, Cecilia / Mamanova, Lira / Bolt, Liam / Richardson, Laura / Polanski, Krzysztof / Madissoon, Elo / Barnes, Josephine L / Allen-Hyttinen, Jessica / Kilich, Eliz / Jones, Brendan C / de Wilton, Angus / Wilbrey-Clark, Anna / Sungnak, Waradon /

Prett, Jan Patrick / Prigmore, Elena / Yung, Henry / Mehta, Puja / Saleh, Aarash / Saigal, Anita / Chu, Vivian / Cohen, Jonathan M / Cane, Clare / Iordanidou, Aikaterini / Shibuya, Soichi / Reuschl, Ann-Kathrin / Argento, A. Christine / Wunderink, Richard G / Smith, Sean B / Poor, Taylor A / Gao, Catherine A / Dematte, Jane E / NU SCRIPT Study Investigators / Reynolds, Gary / Haniffa, Muzlifah / Bowyer, Georgina S / Coates, Matthew / Clatworthy, Menna R / Calero-Nieto, Fernando J / Gottgens, Berthold / O'Callaghan, Christopher / Sebire, Neil J / Jolly, Clare / de Coppi, Paolo / Smith, Claire M / Misharin, Alexander V / Janes, Sam M / Teichmann, Sarah A / Nikolic, Marko Z / Meyer, Kerstin B

medRxiv

Abstract: While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection ... ...

Abstract	While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in pediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data as a highly granular reference for the study of immune responses in airways and blood in children.
Keywords	covid19
Language	English
Publishing date	2021-03-15
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.09.21253012
Database	COVID19

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