tof wagner reference center for rare diseases department of internal medicine … · 2020. 5....
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TOF WagnerReference Center for Rare DiseasesDepartment of Internal Medicine 1
Universitätsklinikum FrankfurtGoethe Universität FrankfurtFrankfurt am Main, Germany
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
1. We do really know only a little bitFew COVID-19 data available – most is extrapolated from experience and other (similar) diseases
2. We know that answers are neededEducated guessing – plausibility – with all necessary caution
3. Exchange of experience among ‘experts’ is only the first step on the way to get to know this disease and its risks
4. Thanks toEuropean Commission for the initiative and for providing the platformThe experts – having not time to spare – for being hereThe attendants for joining us
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsAll speakers are active members of ERN-LUNG, i.e. the European Reference Network for Rare Diseases of the Respiratory System, bringing together more than 100 experts from all over Europe.
There are 24 ERNs funded by the European Commission
ERN-LUNG is being organized in 9 Core Networks, i.e. Cystic Fibrosis, Interstitial Lung Disease, Pulmonary Hypertension, Alpha-1-Antitrypsin Deficiency, non-CF Bronchiectasis, Primary CiliaryDyskinesia, Mesothelioma, Chronic Lung Allograft Dysfunction, and Other Rare Lung Diseases.
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Where can we find the right info?
National authorities / institutions
They come to their conclusions and regulations on the basis of scientific data and other sources
How to find scientific data?
ERS / ELF
ERS COVID-19 resource centre
https://www.ersnet.org/the-society/news/novel-coronavirus-outbreak--update-and-information-for-healthcare-professionals
ERS Guideline and recommendations directory
https://www.ersnet.org/covid-19-guidelines-and-recommendations-directory
ERS Guideline and recommendations directoryAs of April 29, 2020 n=82 such recommendations have been collected
https://www.ersnet.org/covid-19-guidelines-and-recommendations-directory
European Lung Foundation
https://www.europeanlung.org/en/QA-covid-19
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Where can we find the right info?
National authorities / institutions
They come to their conclusions and regulations on the basis of scientific data and other sources
How to find scientific data?
ERS resource center / ELF
guidelines & recommendations / publications / advice
How about Rare Diseases?
EXABO - Expert Advisory Board of ERN-LUNG
= Online Expert advice system for care team members and patients
EXABOExpert Advisory Board ERN-LUNGwww.exabo.eu
Idea: • Easy access to quality assured info• Trustworthy online advice• In all European Member States• For every rare disease of the respiratory system• In all native languages
MODEL: ECORN-CF • Started as an EU pilot project• More than 10 years now – financially supported by patient
organizations
EXABO:• Since 2019• Until now only in English und German• All diseases of the respiratory tract (ERN-LUNG)
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Your Questions
During the webinar: write a short note using the webex tool
If we cannot answer your questions during the webinar, we will try to do so after the webinar. In that case please, go to
www.exabo.eu or visit www.ERN-LUNG.eu
Follow instructions – select the rare disease of the respiratory system the question relates to, ask your question there, and we will try our best to answer quickly…
After the webinar: if you have a question related to rare respiratory diseases -in the context of COVID-19 or not-, go to
www.exabo.eu or visit www.ERN-LUNG.eu
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Preface
Who is going to answer your questions?
Speakers / Experts / Topics
Where can we find the right info?
National authorities / ERS / EXABO
Your Questions
During the webinar / after the webinar
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
COVID-19 in patients with rare diseasesof the respiratory system:
Cystic Fibrosis
ERN-LUNG & ERS joint webinar, 30 April 2020
I. Fajac, Paris, France
No early information from China on COVID-19 in patients with CF as prevalence of CF isextremely low in Asian population
Usually in CF, viral respiratory tract infections are more severe than in the general population: increased risk of complications and negativeimpact on lung function
Prevalence of COVID-19 in patients with cystic fibrosis (CF)
Colombo et al, Lancet Resp Med, 15 Apr 2020
ESCF: 2075
CF & COVID: 3
FRCF: 6940
CF & COVID: 5
DECF: 6119
CF & COVID: 5
UKCF: 10468
CF & COVID: 7
ITCF: 5565
CF & COVID*: 10*Lombardia
So far: Few reported cases of COVID-19 in patients
with CF Mild COVID-19 disease No apparent effect on CF disease severity
Preliminary and incomplete reporton patients with CF and COVID-19
Data from the ECFS Registry, 28 Apr 2020Data collection on-going by the ECFS-Registry
0 5 10 15 20
Critical
Severe
Mild
Number of patients
COVID-19 disease severity
No death
COVID-19: Guidelines for patients with cystic fibrosis (CF)
1) Recommend preventive measures already well-established in that population: Social distancing, use of face masks and adequate hand hygiene
2) Prevent unnecessary hospital visits and viral spread: Cancel routine clinic appointments Procedures such as respiratory function testing put on hold
3) Open lines of communication with CF centre: Regular video-consultations with CF physician to assess CF disease Self-monitoring: home spirometry or oxygen saturation, sputum analysis Continue usual treatment including airway clearance +++
4) Think of COVID-19 disease if mild change of symptoms: Low threshold for testing for SARS-CoV-2 Inform Intensive Care Units so that CF is not deemed of lower priority for
critical care or ventilator utilization (Ramos et al, AJRCCM 14 Apr 2020)
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
ERS/ATS, Am J Respir Crit Care Med Vol 188, Iss. 6, pp 733–748, Sep 15, 2013; King et al. Am J Respir Crit Care Med. 2000;161:646; 2. Travis et al. Am J Respir CritCare Med. 2002;165:277. 3. ATS/ERS Guideline. IPF: Diagnosis and Treatment. 2000; 4. ATS/ERS Guideline. Classification of the Idiopathic Interstitial Pneumonias. 2002; 5. Harrison’s Principles of Internal Medicine 17th ed.
RB-ILD: respiratory
bronchiolitis ILD
Teramachi et al., Resp Med 2018Collard et al, AJRCCM 2017; Kreuter et al., Eur Res J, 2020
AE-IPF
Infection in IPF with AE-IPF
NY-experience
Risk factors for In-hospital mortality:
older age
hypertension
chronic lung disease (9%)
COPD
ILD, aHR 4.22 (95% CI 2.02-8.84)
Cummings MJ et al. 2020 DOI org/10.1101/2020.04.15.20067157 )
Gandhi RT et al., NEJM 2020, DOI: 10.1056/NEJMcp2009249, www.who.int
Patient characteristics of hospitalised COVID-19 patients with and without ARDS
Dreher et al Dtsch Arztebl Int 2020; 117: 271–8
ILD treatments:
Depending on subtype: antifibrotic therapy, immunsuppressive therapy, …
Potential risk of immunosuppression
Viral infections (e.g. adenovirus / influenza) may result in more severe disease inimmunocompromised patients
Patients under immunosuppression did not appear to be at higher risk of severe affections during past coronavirus outbreaks (SARS / MERS)
Casuistics in COVID-19: Complication rate low ?
Some immunomodulators may show benefit in certain subgroups of COVID-19-associated severe ARDS - cytokine storm syndrome ?
Kaltsas A, et al. Curr Opin Infect Dis. 2012;25(4):423-430; D'Antiga L. Liver Transpl. 2020Mihai et al. Ann Rheum Dis 79:668-669, 2020; Mehta et al., Lancet 20202; 395:1033-1034
Potential approach, expert & patient statements
Continue indicated immunosuppression to control ILD
avoids high dose steroid rescue therapy in case of progression
In case of SARS-CoV2 infection re-assess / interrupt therapy
Continue non-immunsuppressive therapies
In case of COVID-19 ILD / respiratory diseases consider symptomatic
therapy
Bauer T et al., German Respiratory Society Statement 2020 / www.pneumologie.de; www.thelamfoundation.orgBajwah et al., Eur Res J, 2020 in press
Continued uncertainties in the use of common ILD pharmacotherapies
Restricted access to timely diagnosis / diagnostic procedures
Delay in therapy initiation with impaired outcomes
Potential mismanagement
Limited ability to monitor disease and drug associated adverse effects
Overseen acute exacerbations & disease progression
Significantly reduced research activities
Wong et al., Chest 2020, /doi.org/10.1016/j.chest.2020.04.019 in press
Conclusion: take care & be aware caring for the rare
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
COVID-19 infection in lung transplant patients
Prof Geert M. Verleden, MD, PhD, FERS
Head of the Respir Dis Dept, University Hospital Leuven, Belgium
Co-chair ERN-LUNG CLAD core network
On behalf of the CLAD ERN group
Current Global Situation
• COVID-19 in solid organ transplant patients• Case reports and small series in
• Liver transplantation
• Kidney transplantation variable outcome
• Heart transplantation
• No data in lung transplant patients• Pereira et al. AJT, ahead of print
• 90 SOT patients
• 19 lung transplant patients, but no separate analysis available
ERN-LUNG CLAD experience
• Hannover/Essen 6 patients• 2 recovered, 2 died, 2 in hospital, one on ECMO
• Pavia 4 patients• all recovered
• Leuven 10 patients (1.5% of the total cohort)• 7 recovered, 1 died, 2 still in hospital with mild disease
Leuven experiencewith COVID-19 after LTx
MaleObeseDiabeticArt. hypertensionRenal insuffic.
Take home messages
• IS treatment does not need to be stopped (at least CNI and CS)
• Mostly mild tot moderate disease, with good chance of recovery
• Prevalence higher compared to general population, outcome same?
• Not all IS patients with fever and ground glass on chest CT have COVID-19
• Collateral damage:• Number of donors decreased to 20%
• Lung transplant program had to be stopped in a lot of centers
• Effect of COVID-19 on development of CLAD is unknown
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
Marc HUMBERT, MD, PhDReference Center for Pulmonary Hypertension
Department of Respiratory and Intensive Care MedicineInserm UMR_S 999
Hôpital Bicêtre (Assistance Publique – Hôpitaux de Paris)RespiFIL, ERN-LUNG
Université Paris-SaclayLe Kremlin-Bicêtre, France
• Definition : chronic elevation of mean pulmonary artery pressure (mPAP)
• Normal values of mPAP are 14 + 3 mmHg (abnormal > 20mmHg, PVR>3WU)
• Consequence : right heart failure and death
Pulmonary Hypertensiona cardiopulmonary condition
CLINICAL CLASSIFICATION OF PH
1.1 Idiopathic PAH1.2 PAH with vasoreactivity1.3 Heritable PAH1.4 Drugs and toxins induced1.5 Associated with:
1.5.1 Connective tissue disease1.5.2 HIV infection1.5.3 Portal hypertension1.5.4 Congenital heart disease1.5.5 Schistosomiasis
1.6 PAH with overt features of venous/capillaries(PVOD/PCH) involvement
1.7 Persistent PH of the newborn syndrome
1. Pulmonary Arterial Hypertension
2.1 PH due to heart failure with preserved ejection fraction 2.2 PH due to heart failure with reduced ejection fraction2.3 Valvular heart disease2.4 Congenital post-capillary obstructive lesions
2. PH due to left heart disease
3.1 Obstructive lung disease3.2 Restrictive lung disease3.3 Other lung disease with mixed restrictive/obstructive pattern 3.4 Hypoxia without lung disease3.5 Developmental lung disorders
3. PH due to lung diseases and/or hypoxia
4.1 Chronic thromboembolic PH4.2 Other pulmonary artery obstructions
4. PH due to pulmonary artery obstruction
5.1 Haematologic disorders5.2 Systemic disorders 5.3 Others5.4 Complex congenital heart disease
5. PH with unclear mechanisms
Simonneau G, et al. Eur Respir J 2019; 53:1801913
44
• Definition : chronic precapillary pulmonary hypertension
• Cause : progressive structural remodeling of the small pulmonary arteries
• Consequence : right heart failure and death
Normal PAH
Pulmonary Arterial Hypertension : a severe pulmonary vascular disease
Pulmonary Arterial Hypertension : a rare, but not an orphan disease
• Rare: prevalence 15–50/million (incidence 6/million/year)
• Pathophysiology: pulmonary artery endothelial cell dysfunction…
• Drugs: 14 agents approved in the last 20 years (orphan drug status)
• Lung/heart–lung transplantation: if refractory to medical therapy
➚ ET-1
➚ 5-HT
Endothelial
cell
SMCs
➚ FGF-2
1. Are people with PH at greater risk for COVID-19 virus infection?
2. What safety precautions should I take as a PH patient?
3. Is it safe for me to go to work or my children to go to school?
4. What should I do if I am worried that someone I live with may be at risk of being infected due to their work or other circumstances (e.g.
spouse works in a medical setting or in a profession in frequent contact with other)?
5. Is it safe for me or my family member to have an in-person visit with my doctor or schedule non-emergency medical procedures?
6. What should I do if I am currently participating in a clinical trial?
7. How do I know if my breathing issues are due to PH or COVID-19?
8. Are there treatments available for COVID-19?
9. Should I worry about running out of medicine or supplies?
10. COVID-19 has caused a lot of anxiety for me and my family. What can I do?
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Who is here to answer your questionsThomas O. F. Wagner (Frankfurt, Germany)
Coordinator of ERN-LUNG
Isabelle Fajac (Paris, France)
President of the European Cystic Fibrosis Society (ECFS) and Member of ERN-LUNG
Michael Kreuter (Heidelberg, Germany)
Co-Chair of the ILD Core Network of ERN-LUNG
Geert Verleden (Leuven, Belgium)
Co-Chair of the Chronic Lung Allograft Dysfunction Core Network of ERN-LUNG
Marc Humbert (Paris, France)
Vice-President of the ERS, Vice-Coordinator of ERN-LUNG and co-Chair of the PH Core Network of ERN-LUNG
Heymut Omran (Münster, Germany)
Co-Chair of the PCD Core Network of ERN-LUNG
Primary Ciliary Dyskinesia (PCD) and COVID
Heymut OmranUniversity Hospital Muenster, Germany
In behalf of the PCD Core of the European Reference Network on Rare Lung Diseases
ERN-LUNG
COVID19 clinical management support system (COVID19 -CMSS)
• Privacy Statement
• Recording is allowed!!!
54Figure adapted from Ibañez-Tallon et al. 2003 and Teveset al. 2016
Cilia in the Human Body
Structure of motile Cilia
Trends Genet. 19:162-7, 2003; Hum Mol Genet 12: R27-35, 2003
Healthy Person PCD Patient
Radiologische BefundeClinical Findings in PCD
57
PCD and COVID-19
PCD Centers that responded to question whether they have/had experience with PCD andCOVID-19:
Austria: ViennaBelgium: LeuvenCyprus: NicosiaDenmark: CopenhagenFrance: ParisGermany: Berlin, Hannover, MünsterItaly: Napoli, Pisa, RomeLatvia: RigaPoland: RabkaSpain: BarcelonaUK: London, Southampton
58
PCD and COVID-19
PCD support group information (Bernhard Rindlisbacher)
US Facebook group:“I am 21, and I came back positive and I am a PCD patient.I was tested due to a high risk exposure and I was with that person for their whole covid experience and so I was tested for that reason. I never developed any symptoms, I was put on azithromycin but other than that, I didn’t develop any symptoms; not even a cough and I usually always have a cough.”
2) German speaking group on Facebook:“My husband and I both tested positive. We've been in quarantine for three weeks and we're getting better now. Our children (2 and 5 years old), one of whom has PCD, both tested negative, although we had close contact with them. Our children were tested 16 days after our first symptoms, when our tests were still positive. Either they have already endured the virus or they have not been infected by us. Our children had coughed a little more in the last three weeks, otherwise we didn't notice anything. Obviously at least the children are spared in most cases.”
59
PCD and COVID-19
Jean-François PAPON (Paris, France)
„From march 27th to april 25th, I followed one of my PCD patient with COVID-19. He is a 40 years old DNAH9-mutated patient with a situs inversus and very moderate disease (nobronchiectasis, normal nasal NO, normal ENT exam and normal FEV1). This probably explainwhy he was not so strict regarding quarantine.
The initial symptoms started on march 27th (myalgia, fatigue, thorax pain, diarrhea, sorethroat but no dyspnea, fever or smell disorders). I called his pulmonologist and a follow-upwas decided (no COVID-testing or CT-scan). We had daily phone calls and, at day 3, he reported dyspnea and exhaustion. I called the "Paris medical emergency unit" who went at his home and fund no signs of respiratory distress (AP = 12/7; HR = 85 ; RR = 20 ; saturation = 99% in AA ; Glasgow = 15 ; dry cough). He prescribed pristinamycin for 1 week. From day 4 to7 he reported fatigue (12 to 13 hours sleep every night) and improvement of other symptoms(and no new symptoms). I called him on april 25th, dyspnea and fatigue stopped since day 21 and he is perfectly well today.“
60
Summary: PCD and COVID-19
• Lack of COVID-19 in PCD individuals due to strict quarantine• Currently limited data available for reliable prediction of the
clinical course• Plan: Data collection of clinical courses of PCD individuals with
COVID-19 using the ERN-LUNG PCD registry
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Your Questions
Feel free to ask your questions
• Do you recommend to patients having therapy for their rare lung condition that they should continue attending hospital to receive their treatment or is it better to go without for some weeks/months until the risk of infection diminishes?
Question to the experts
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Question to the experts
• It seems that children are less often infected by COVID-19 and especially that the course of the disease is on average less severe in children than in adults. Most children are said to be infected by adults, e.g. their parents. Now gradually the schools will open again and many fathers or mothers with rare disease (in this case the question came from PCD) are afraid that their children might bring the infection home from school. However, there are experts that say this is very unlikely as until now there are no or hardly any cases known where children did infect their parents. Please let us know what you as expert think about the risk for parents to be infected by their children.
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
ERN-LUNG and ERS joint webinar: COVID-19 in
patients with rare diseases of the respiratory system
Your Questions
During the webinar: write a short note using the webex tool
If we cannot answer your questions during the webinar, we will try to do so after the webinar. In that case please, go to
www.exabo.eu or visit www.ERN-LUNG.eu
Follow instructions – select the rare disease of the respiratory system the question relates to, ask your question there, and we will try our best to answer quickly…
After the webinar: if you have a question related to rare respiratory diseases -in the context of COVID-19 or not-, go to
www.exabo.eu or visit www.ERN-LUNG.eu