Harsita Patel (United Kingdom)

Imperial College London Infectious Disease
I am a paediatric trainee in London, interested in infectious disease and global health. I am currently undertaking a PhD at Imperial College London, supervised by Professor Michael Levin and Dr Vanessa Sancho Shimizu. My research is focussed on understanding the immunopathology in SARS-CoV-2 associated disease in children, including multisystem inflammatory syndrome in children.

Author Of 5 Presentations

Case 2 - Childhood Infections – How Many is Too Many?

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:27 - 07:49

NO EVIDENCE OF AUTO-ANTIBODY BINDING TO CARDIAC TISSUE IN MIS-C AND COVID-19 VACCINATION INDUCED CARDIOMYOPATHY

Date
Wed, 11.05.2022
Session Time
10:00 - 11:02
Session Type
Oral Presentations Session
Room
BANQUETING HALL
Lecture Time
10:32 - 10:42

Abstract

Backgrounds:

Cardiomyopathy is one of the significant features of SARS-CoV-2 induced multi-system inflammatory syndrome in children (MIS-C) and it is also a rare complication of mRNA COVID-19 vaccination in young adults. MIS-C occurs 4-6 weeks following SARS-CoV-2 infection; we therefore postulated that antibodies might play a role in the cardiac immunopathology. The mechanism of vaccine-induced myocarditis is currently being explored. We investigated the role of anti-cardiac antibodies in post SARS-CoV-2 vaccine myocarditis and MIS-C.

Methods:

Clinical cohort: Pre-treatment acute MIS-C (n=10), acute COVID-19 vaccination-induced myocarditis (n=10), Pre-COVID-19 pandemic healthy children (n=10) and healthy COVID-19 vaccinated adults (10).

Immunohistochemistry was performed on human left ventricular tissue sections from 2 donor hearts (deemed unsuitable for donation) for assessment of auto-antibody binding. Sera from patients and controls were used as primary antibodies. FITC-conjugated anti-human-IgG (1:150), IgM (1:150) and IgA (1:50) were used for detection. 10 images were taken at random from each section and immunoglobulin deposition was quantified by calculating mean fluorescent intensity using ImageJ/Fiji. This method has previously shown specific binding of IgG to cardiac tissue following treatment with serum obtained from an adult myocarditis patient.

Results:

No specific binding was seen in left ventricular tissue treated with sera from paediatric patients with either MIS-C or COVID-19 vaccine-induced myocarditis. There was no significant difference in the mean fluorescent intensity of IgG, IgM and IgA in patients compared to controls (Figure 1).

figure1.png

Conclusions/Learning Points:

Our study did not find evidence for a role of an anti-cardiac antibody-mediated inflammatory process in MIS-C cardiomyopathy and COVID-19 vaccine induced myocarditis.

Hide

Young ESPID Coordinator

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:00 - 07:00

T CELL EXHAUSTION IS A FEATURE OF MIS-C RELATED IMMUNE REPONSES

Date
Wed, 11.05.2022
Session Time
13:40 - 15:10
Session Type
Parallel Symposium
Room
ALEXANDRA TRIANTI HALL
Lecture Time
14:47 - 14:57

Abstract

Backgrounds:

T cell lymphopaenia, and activation are well described features of MIS-C. We evaluated whether T cell exhaustion alongside T cell activation reported in childhood viral infections, occurs in children with a clinical diagnosis of MIS-C.

Methods

Clinical cohort: Children with febrile illnesses and healthy controls were recruited from two tertiary London hospitals between 01/09/2020-31/12/21, as part of the EU-funded DIAMONDS study. 162 participants were included: MIS-C (n=80), COVID-19 pneumonitis (n=7), Kawasaki disease (n=3), severe viral (n=7), and bacterial (n=19) illness, other inflammatory (n=8), paediatric controls (n=13), and adult vaccinated controls (n=25). Eighty-two of 124 patients (66%) required intensive care.

Samples were collected at two time-points: acute illness at admission and convalescence. Qiagen SARS-CoV-2 QuantiFERON kits were used for stimulation of whole blood with mitogen and SARS-CoV-2 antigens, to stimulate CD4+ and CD8+ T cells, and subsequent measurement in the supernatant of IFNγ levels.

Results:

The QuantiFERON assay was performed on 132 samples (acute n=59, convalescence n=19, paediatric controls n=11, adult controls n=25). MIS-C patients had raised baseline IFNγ levels, with lower increase after stimulation with SARS-CoV-2 antigens compared to vaccinated adults. The absolute increase in IFNγ in response to mitogen was lower in MIS-C compared to vaccinated adults, healthy children or bacterial infection. There was recovery in mitogen response in MIS-C in convalescence (Figure 1).

mis-c_quantiferon_image.png

Conclusions/Learning Points:

We report a high baseline IFNγ and low activation by SARS-CoV-2 peptides and mitogen, which suggests T cell exhaustion coexists with features of T cell activation in MIS-C. Further studies on molecular mechanisms of T cell exhaustion are warranted.

Hide

Case 1 - A Young Child with Persistent Fever and Anaemia

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:05 - 07:27

Presenter Of 5 Presentations

Case 2 - Childhood Infections – How Many is Too Many?

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:27 - 07:49

NO EVIDENCE OF AUTO-ANTIBODY BINDING TO CARDIAC TISSUE IN MIS-C AND COVID-19 VACCINATION INDUCED CARDIOMYOPATHY

Date
Wed, 11.05.2022
Session Time
10:00 - 11:02
Session Type
Oral Presentations Session
Room
BANQUETING HALL
Lecture Time
10:32 - 10:42

Abstract

Backgrounds:

Cardiomyopathy is one of the significant features of SARS-CoV-2 induced multi-system inflammatory syndrome in children (MIS-C) and it is also a rare complication of mRNA COVID-19 vaccination in young adults. MIS-C occurs 4-6 weeks following SARS-CoV-2 infection; we therefore postulated that antibodies might play a role in the cardiac immunopathology. The mechanism of vaccine-induced myocarditis is currently being explored. We investigated the role of anti-cardiac antibodies in post SARS-CoV-2 vaccine myocarditis and MIS-C.

Methods:

Clinical cohort: Pre-treatment acute MIS-C (n=10), acute COVID-19 vaccination-induced myocarditis (n=10), Pre-COVID-19 pandemic healthy children (n=10) and healthy COVID-19 vaccinated adults (10).

Immunohistochemistry was performed on human left ventricular tissue sections from 2 donor hearts (deemed unsuitable for donation) for assessment of auto-antibody binding. Sera from patients and controls were used as primary antibodies. FITC-conjugated anti-human-IgG (1:150), IgM (1:150) and IgA (1:50) were used for detection. 10 images were taken at random from each section and immunoglobulin deposition was quantified by calculating mean fluorescent intensity using ImageJ/Fiji. This method has previously shown specific binding of IgG to cardiac tissue following treatment with serum obtained from an adult myocarditis patient.

Results:

No specific binding was seen in left ventricular tissue treated with sera from paediatric patients with either MIS-C or COVID-19 vaccine-induced myocarditis. There was no significant difference in the mean fluorescent intensity of IgG, IgM and IgA in patients compared to controls (Figure 1).

figure1.png

Conclusions/Learning Points:

Our study did not find evidence for a role of an anti-cardiac antibody-mediated inflammatory process in MIS-C cardiomyopathy and COVID-19 vaccine induced myocarditis.

Hide

Young ESPID Coordinator

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:00 - 07:00

T CELL EXHAUSTION IS A FEATURE OF MIS-C RELATED IMMUNE REPONSES

Date
Wed, 11.05.2022
Session Time
13:40 - 15:10
Session Type
Parallel Symposium
Room
ALEXANDRA TRIANTI HALL
Lecture Time
14:47 - 14:57

Abstract

Backgrounds:

T cell lymphopaenia, and activation are well described features of MIS-C. We evaluated whether T cell exhaustion alongside T cell activation reported in childhood viral infections, occurs in children with a clinical diagnosis of MIS-C.

Methods

Clinical cohort: Children with febrile illnesses and healthy controls were recruited from two tertiary London hospitals between 01/09/2020-31/12/21, as part of the EU-funded DIAMONDS study. 162 participants were included: MIS-C (n=80), COVID-19 pneumonitis (n=7), Kawasaki disease (n=3), severe viral (n=7), and bacterial (n=19) illness, other inflammatory (n=8), paediatric controls (n=13), and adult vaccinated controls (n=25). Eighty-two of 124 patients (66%) required intensive care.

Samples were collected at two time-points: acute illness at admission and convalescence. Qiagen SARS-CoV-2 QuantiFERON kits were used for stimulation of whole blood with mitogen and SARS-CoV-2 antigens, to stimulate CD4+ and CD8+ T cells, and subsequent measurement in the supernatant of IFNγ levels.

Results:

The QuantiFERON assay was performed on 132 samples (acute n=59, convalescence n=19, paediatric controls n=11, adult controls n=25). MIS-C patients had raised baseline IFNγ levels, with lower increase after stimulation with SARS-CoV-2 antigens compared to vaccinated adults. The absolute increase in IFNγ in response to mitogen was lower in MIS-C compared to vaccinated adults, healthy children or bacterial infection. There was recovery in mitogen response in MIS-C in convalescence (Figure 1).

mis-c_quantiferon_image.png

Conclusions/Learning Points:

We report a high baseline IFNγ and low activation by SARS-CoV-2 peptides and mitogen, which suggests T cell exhaustion coexists with features of T cell activation in MIS-C. Further studies on molecular mechanisms of T cell exhaustion are warranted.

Hide

Case 1 - A Young Child with Persistent Fever and Anaemia

Date
Wed, 11.05.2022
Session Time
07:00 - 07:50
Session Type
Meet The Experts
Room
NIKOS SKALKOTAS HALL
Lecture Time
07:05 - 07:27