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Covid-19 - Excerpts from the upcoming ERS
Monograph on Covid-19
ERS Webinar 15 th June 2021
ERS Webinar 15 th June 2021

Covid-19 - Excerpts from the upcoming ERS Monograph on Covid-19

Speakers:
Chairs:
P rof. A ure li e Dr Sheila Ramjug Ms. Leanna Lui P r o f. A n i t a M r. F r a n c e s c o
Fabre H BS c, Un iversity of Simonds A m a ti
To r o n t o , O n t a r i o , E RS P residen t Department of
Consultant Assembly 13
Canada 2020-21 Patho physiolo gy
Histopathologist Early Career and
UCD Full Clinical Member Incoming MSc Professor of
Tr a n s p l a n t a ti o n ,
Professor R e p r e s e n t a ti v e Candidate, Respirator y an d University of
University College Consultant I n s ti t u t e o f Sleep Medicine, Milan; Internal
Dublin School of Pulmonologist Medical Science, Royal Brom pton Medicine
Medicine with an interest University of a n d H a r e fi e l d Department,
To r o n t o , O n t a r i o , N H S F o u n d a ti o n Respirato ry Unit
S t V i n c e n t ’s in pulmonary
Canada Tr u s t , L o n d o n a n d C y s ti c F i b r o s i s
University vascular disease A d u l t C e n t e r.
Hospital Manchester Mood Disorders UK
Fondazione IRCCS
Dublin University NHS Psychopharmacolo Ca' Granda
Ireland F o u n d a ti o n T r u s t gy Un it, University Ospedale Maggiore
Health Network, Policlinico, Milan,
Canada Italy

Programme:
1- Introducti on f rom the chairs – 2 mi nutes
2- The COVID -1 9 Syndem ic: Econom ic, Social a nd Biologic D eter minants of Health - Le anna Lui
     - 1 4 minutes
3- COVID -1 9 Vaccines – regulati on and clinical manageme nt – Anita Si monds - 1 4 minutes
4- Post COVID -1 9 sequalae -   France sco Amati – 1 4 Minu te s
5 - Q&A – 1 5 m inutes
5- Wrap- up and closing – 1 m inute
The COVID-19 Syndemic: Economic, Social and
Biologic Determinants of Health

Leanna M.W. Lui

University of Toronto, Ontario, Canada

Mood Disorders Psychopharmacology Unit, University Health Network, Canada
 Conflict of Interest Disclosure

I have no real or perceived conflicts of interest that relate to this presentation.

Affiliation / Financial interest Commercial Company

Grants/research support: N/A

Honoraria or consultation fees: N/A

Participation in a company sponsored bureau: N/A

Stock shareholder: N/A

Spouse / partner: N/A

Other support / potential conflict of interest: Braxia Scientific Corp

This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker
with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a
presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or
relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the speaker’s
presentation. Drug or device advertisement is forbidden.
 Introduction
AIMS
• Gendered effect of COVID-19 on the economy
• Implications of COVID-19 on mental health and suicide
• Understanding COVID-19 as a social virus
 Global Economic Outlook for 2021-2022
• International Monetary Fund (IMF) projects 6% growth for 2021 and
4.4% growth for 2022
• Divergent recovery paths in advanced and developing economies
– Widening gaps in living standards
– Augmenting within-country income inequality
– Increasing the number of people in poverty
 MCQ 1 (Poll)

What is the She-Session?

a) Increased burden of unpaid work (“care economy”)

b) Consequence of economic downfall endured by women
c) A rise in suicide rates among women
d) Increase in loneliness among women
 What is the She-Session?
Unemployment Rate in Advanced Unemployment Rate in Developing
Economies Economies

World Economic Outlook International monetary fund Managing divergent recoveries. April
2021. ISSN 0256-6877 (print) | ISSN 1564-5215 (online)
The Relationship Between Decreased Occupational Flexibility and
the Care Economy

Childcare

Poor mental
health
outcomes,
Provision of
increased elderly
suicidality

Missed job Increased

opportunities stress
 Financial Security is a Key Mediator of Mental Health
Elevated Risk of Suicide Among Females

Sakamoto et al., JAMA Netw Open. 2021 Feb 1;4(2):e2037378. doi: 10.1001/jamanetworkopen.2020.37378.

 COVID-19 and Suicide in the General Population
Projected Suicide Rates in Canada During COVID-19

McIntyre RS, Lee Y. Psychiatry Res. 2020 Aug;290:113104. doi: 10.1016/j.psychres.2020.113104. Epub 2020 May

Magnifying the Loneliness and Addiction Epidemic
• Prolonged quarantine and lockdown measures have worsened
the loneliness epidemic (e.g., Long-term care homes)
• Exacerbated the substance use disorder crisis
• Health care delivery challenges
A Digital (Social) Virus

Health
implications

Social Digital
exclusions inequities
 Conclusion
• Augmented economic and social determinants of health which
portend poor mental and physical outcomes
• Experts outside of medicine to implement appropriate social and
welfare protections
• Pivot towards the 3Es:
– Economic stability
– Education
– Equality
The COVID-19 Syndemic: Economic, Social and
Biologic Determinants of Health

Leanna Lui

University of Toronto, Ontario, Canada

Mood Disorders Psychopharmacology Unit, University Health Network, Canada
 Vaccines: regulation and clinical management
Anita K Simonds, President ERS 2020-21, Member EMA Covid Task Force

ERS monograph Webinar June 15 (Vaccine immunology: Prof Rosemary Boyton)

 Conflict of interest disclosure
X I have no real or perceived conflicts of interest that relate to this presentation.

 I have the following real or perceived conflicts of interest that relate to this presentation:

Affiliation / Financial interest Commercial Company

Grants/research support:

Honoraria or consultation fees:

Participation in a company sponsored bureau:

Stock shareholder:

Spouse / partner:

Other support / potential conflict of interest:

This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker
with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a
presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or
relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the speaker’s
presentation. Drug or device advertisement is forbidden.
Introduction

AIMS
Aim 1 Appreciate new processes in vaccine regulation
Aim 2 Understand vaccine efficacy, efficiency and safety monitoring
Aim 3 Review current dilemmas: adverse effects, variants, vaccination in children
Vaccines types

MMR Sinovac Vetinerary AZ Oxford Genzyme Pfizer, Moderna Novavax

J&J Curevac
Vaccine platforms (from monograph chapter)
Whole inactivated virus Viral vectors
Eg Polio vaccine Eg VSV-Ebola vaccine
COVID-19, CoronaVac, BBIBP-CoV (b-propiolactone inactivated virus vaccine with aluminium COVID-19, CanSino, AdH5-nCoV (replication deficient human adenovirus 5 vectored vaccine
hydroxide adjuvant); expressing full length spike);
Sputnik V, rAd26/rAd5 (recombinant adenovirus 26 and 5 vectored vaccines expressing full
Covaxin (b-propiolactone inactivated virus vaccine with TLR7/8 agonist and alum adjuvant); length spike);
Inactivated virus that is no longer infectious. Requires large quantities of virus to be grown
Oxford AZ, ChAdOx1-S-nCoV (replication deficient simian adenovirus vectored vaccine
under biosafety level 3 (BSL3) conditions.
expressing codon-optimised spike protein);
Recombinant virus is used that is attenuated to reduce pathogenicity. Genes encoding viral
antigen are cloned into the viral vector. Can be rapidly adapted as new variants emerge.

Live-attenuated virus DNA

Eg MMR vaccine Inovio, INO-4800 (DNA plasmid vaccine expressing full length spike protein);
Virus is passaged in cell culture until it is less pathogenic and only causes a mild infection Synthetic DNA construct encoding vaccine antigen. After uptake into cells, the antigen is
following vaccination. Requires extensive safety testing to ensure no reversion to wild type. expressed from the DNA construct. Can be rapidly adapted as new variants emerge.

Protein antigen subunit RNA

Eg seasonal flu vaccine COVID-19, Pfizer/BioNTech, BNT162B2 (nucleoside modified mRNA vaccine encoding full
COVID-19, Novavax, NVX-CoV2373 (recombinant nanoparticle vaccine expressing full length length pre-fusion spike protein encapsulated in lipid nanoparticles);
spike protein with matrix M1 adjuvant); Moderna, mRNA-1273 (mRNA vaccine encoding pre-fusion spike protein encapsulated in a
Protein purified from the virus or recombinant protein. Requires an adjuvant to promote lipid nanoparticle);
long lasting immunity mRNA stability improved by including modified nucleosides to prevent degradation. Carrier
molecule (lipid nanoparticles) needed to enable mRNA entry into cells. Multiple dosing.
Can be rapidly adapted as new variants emerge.

Virus-like particles Antigen-presenting cells

Eg Human papillomavirus vaccine Artificial antigen presenting cells loaded with peptides. Cell based vaccine requiring infusion
Structural viral proteins, lacks viral genome and non-structural proteins. Several recombinant makes large scale deployment difficult
proteins produced simultaneously
Why is approval of SARS-Cov-2 vaccines so fast?
Vaccine development

c/o European Medicines Agency

Rolling reviews of vaccines and covid therapies

c/o EMA
Efficacy : Pfizer BionTech Comirnaty vaccine
Efficacyefficacy

https://www.ema.europa.eu/en/docum
ents/assessment-report/comirnaty-epar-
public-assessment-report_en.pdf
 AZ ChAdOx1 vaccine – efficacy severe
disease

SmPC
there were 0 (0.0%; N=5,258) cases of
COVID-19 hospitalisation in participants who
received two doses of COVID-19 Vaccine
AstraZeneca (≥15 days post dose 2) as
compared to 8 (0.2%; N=5,210) for control,
including one severe case (WHO Severity
grading ≥6), reported for control. In all
participants who received at least one dose, as
from 22 days post dose 1, there were 0 (0.0%,
N=8,032) cases of COVID-19 hospitalisation
in participants who received COVID-19
Vaccine AstraZeneca, as compared to 14
(0.2%, N=8,026), including one fatality,
reported for control.
Efficiency - Real-world evidence – prevention of infection and disease

Israel real-world evidence Pfizer-Biontech mRNA vaccine

Pharmacovigilance
Vaccine Monitoring summary (total)
Comirnaty (72k cases) Moderna (2,6k cases) Astrazeneca (9,3k cases)

30

COVID-19 vaccines – EV monitoring

c/o EMA
Safety monitoring of vaccines post-approval
No association with an increased overall risk of thrombotic events with Vaxzevria AZ vaccine.

Very rare cases of VITT - Vaccine induced immune Thrombosis with thrombocytopenia

PRAC April plenary 2

meeting and the
second PRAC
PRAC validated
PRAC
extraordinary
1 recommendation on
Dissemination
of the second
the signal meeting and the Thromboembolic DHPC in the
Embolic and first PRAC events with EU/EEA
Dissemination
thrombotic recommendation of the first thrombocytopenia
event (DLP 17 March DHPC in the 29 March
22 March
2021) EU/EEA 2021
2021
Second communication:
Thromboembolic events with thrombocytopenia
should be listed as very rare side effects of
First communication Vaxzevria The reported cases were almost all in
No association with an increased women under 60.
overall risk of blood clotting
disorders.

There have been very rare cases 24 March 6 -9 April 7 April 13 April
11/12 18 March of unusual Thromboembolic
2021 Ad hoc Expert meeting 2021 2021 2021
March 2021 events with thrombocytopenia
To discuss hypothesis, https://www.ema.europa.eu/en/news/astraz
after vaccination. The reported
pathophysiological enecas-covid-19-vaccine-ema-finds-possible-
2021 https://www.ema.europa.eu/en/ne
cases were almost all in women
mechanisms, and possible link-very-rare-cases-unusual-blood-clots-
ws/covid-19-vaccine-astrazeneca- under 55.
underlying risk factors, gaps low-blood
benefits-still-outweigh-risks-despite-
Update EV in knowledge and additional
possible-link-rare-blood-clots
search DL studies
22/3/21
c/o EMA
ISTH (1/2)

https://www.isth.org/resource/resmgr/news/ISTH_VITT_Flow_Chart_Final.pdf
 ISTH (2/2)

“DO NOT WAIT for results if

diagnosis of VITT seems
likely.”

https://www.isth.org/resource/resmgr/news/ISTH_VITT_Flow_Chart_Final.pdf
Risk contextualisation of vaccination with AZ vaccinr (Vaxzevria)

c/o
EMA
 Vaccines and correlates of protection
From: ERS Covid
Monograph
Vaccine chapter

Altmann, Boyton & Gleason Science 2021;371:1103-1104

 Vaccines and variants of concern

Increased breakthrough rates

of SARS-CoV-2 variants of
concern in BNT162b2 mRNA
vaccinated individuals

https://doi.org/10.1101/2021.04.06.21254882
Delta variant more transmissible and more hospitalisations…
c/o EMA Continued role for social distancing
 Efficiency demonstrated: Pfizer BionTech, other trials in progress

Role in children with comorbidities

SARS-Cov-2 Small number of adverse effects: eg. myocarditis

Vaccination Impact of new variants on children, incidence of multisystem

inflammatory syndrome and long covid..?

in children Prevention of transmission – role in ‘herd immunity”..?

Effects on schooling higher education, social life

BUT should we vaccinate children ahead of high risk adults & HCW
in low resource settings?? - A societal question
POLL

• All children should be offered covid vaccination as soon as possible

• Only children with comorbidities and high risk conditions should be
offered covid vaccination
• 12-18 year olds should be offered vaccination
• Children should not be vaccinated until high risk adults are
vaccinated (including in low resource settings)
 Thank you

A.Simonds@rbht.nhs.uk @anitaKS1
 POST-COVID SEQUELAE
Francesco Amati
AUTHORS: Gramegna Andrea, Mantero Marco, Amati
Respiratory Unit and Adult Cystic
Francesco, Aliberti Stefano, Blasi Francesco
Fibrosis Center Fondazione IRCCS Ca’ Granda
Ospedale Maggiore Policlinico  Milano
 Conflict of interest disclosure
I have no real or perceived conflicts of interest that relate to this presentation.

This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker with a conflict of
interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners
with information on which they can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or relationships may influence the presentation. The ERS does not
view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the speaker’s presentation. Drug or device advertisement is forbidden.
 Background
AIM OF THE CHAPTER

1. Definition and classification of post-COVID sequelae

2. Description of sequelae
• Cardiorespiratory
• Extra-cardiorespiratory
 Background

Nalbandian A,. Nat Med. 2021;27(4):601-615.

 Background
• Readmission after hospital discharge contributes to the burden of the disease.

• An observational study on 2179 hospitalized patients in Michigan reported readmission

and death within 60 days from discharge in 19.9% and 9.1% of patients, respectively.

• The most common reasons for readmission were COVID-19 (30.2%), sepsis (8.5%),
pneumonia (3.1%) and heart failure (3.1%).

• This observation suggests a period of higher frailty and risk of worse outcomes
immediately after clinical recovery.

Donnelly JP. JAMA 2021

 Definition and classification of post-
COVID sequelae
• When the COVID-19 pandemic began, initial descriptions of the
symptomology focused on the clinical presentations of patients
in the acute, inpatient setting.
• More recently, data have emerged that some patients continue
to experience symptoms after the acute phase of infection.
• There is currently no clearly delineated consensus definition for
the condition: terminology has included “long COVID,” “post-
COVID syndrome” “post-COVID sequelae” and “post-acute
COVID-19 syndrome.”
 Proposed definition and classification

• Time-based

• Severity-based

• Organ-based
 Time-based definition
• COVID-19 acute phase is defined as the time between the onset of symptoms and
hospital discharge (clinical recovery for those who did not require hospitalization).
• Post-COVID phase does not have a clear definition, but it is generally considered as
the period immediately following the recovery without further details on duration
in terms of days or weeks.
• Most of the studies aimed to investigate symptoms and health consequences in
the post-COVID phase included hospitalized patients with a mean follow-up period
of 3 months after discharge from hospital.
Huang C, Lancet. 2021 Jan 16;397(10270):220-232.
Liu X, J Infect. 2020 Jul;81(1):e95-e97.
Carfì A, JAMA. 2020 Aug 11;324(6):603-605.
Time-based definition
 Severity-based definition

• Mild Persistent but reversible symptoms with no need of

treatment.

• Moderate Require active intervention in terms of diagnosis and

treatment but are generally treatable and reversible.

• Severe Represented by chronic organ dysfunction. These

effects are usually long-term and not reversible, or
even progressive.
 Organ-based definition
• Late sequelae of COVID-19 can involve several organs causing different syndromes

that result from distinct pathophysiological processes.

• Different organ involvement in the post-COVID phase in the chapter follows

according to the classification between cardiorespiratory and extra-respiratory

sequelae.
 Organ-based definition
Cardiorespiratory sequelae

ORGAN SEQUELAE QUALITY OF EVIDENCE

Respiratory Pulmonary fibrosis Small observational studies
Lung function decline Multicentre observational studies
Dyspnea Multicentre observational studies
Cardiac Diastolic dysfunction Prospective multicentre
observational studies
Myocardial inflammation Case series
 Organ-based definition
Extrarespiratory sequelae

ORGAN SEQUELAE QUALITY OF EVIDENCE

Haematological Persistent changes in Observational studies
coagulation factors
Neurological Olfactory and gustative Case series and case reports
dysfunction
Neurocognitive alterations Prospective studies
Renal Chronic failure Single large prospective
observational study
Systemic Asthenia and fatigue Prospective observational studies
Thank you!
We would like to thank the participants of this webinar for
their contributions