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1) Long-COVID – Multi-system involvement 2) Respiratory Red Flags in Long COVID Dr TobyHillman – Consultant Physician in the UCLH Post-COVIDServiceDeclaration of Interests ▪ I sit on the NICE Expert Panel on Post-COVID Care ▪ I have received ~£150 in honoraria for talks on Long COVID ▪ I am a member of the STIMULATE-ICPtrial team ▪ I have been diagnosed with Long COVID myself ▪ I have no other intereststo declare 23Post-COVID Care… 4 Multi-Systemeffects of COVID – ACE2 receptorexpression Pericytes and vascular smooth muscle expressACE2 strongly – Karolinska Institute, Sweden doi: https://doi.org/10.1101/2020.05.11.088500 5One year on… 67High dimensional analysis of PACS Nature 594, 259–264 (2021). https://doi.org/10.1038/s41586-021-03553-9Davis, Hannah E et al. “Characterizing long COVID in an international cohort: 7 months of symptoms and their impact.” EClinicalMedicine vol. 38 (2021): 101019. doi:10.1016/j.eclinm.2021.101019t 9Lopez-Leon, S., Wegman-Ostrosky, T., Perelman, C. et al. More than 50 long-term effects of COVID-19: a systematic review and 0 meta-analysis. Sci Rep 11, 16144 (2021). https://doi.org/10.1038/s41598-021-95565-8MRI Findings Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome by gender and hospitalisation. BMJ Open 2021;11:e048391. doi: 10.1136/bmjopen-2020-048391Abnormal exercise physiology ▪ 12% of patients desaturateon STS testingat median 14/52 post illness ▪ Mechanismunclear(73% of these have normal lung and heart imaging) ▪ Some unexpected results on validating walk tests with CBGs ▪ Possibly contributingtobreathlessness and post exercise malaise ▪ Heterogeneous pictureand investigationsare ongoing 12But why?... 13Water, water, every where, And all the boards did shrink; Water, water, every where, Nor any drop to drink. 14Putative pathophysiology Shin Jie Yong (2021) Long COVID or post-COVID-19 syndrome: 15 Putative pathophysiology, risk factors, and treatments, Infectious Diseases, 53:10, 737-754, DOI:10.1080/23744235.2021.1924397Viral PersistenceImmunological Responses in COVID-19 MazzoniA,SalvatiL,MaggiL,Annunziato F,CosmiL.Hallmarksof immuneresponsein COVID-19:Exploring dysregulationand exhaustion [published onlineaheadof print,2021Oct 26]. Semin Immunol.2021;101508.doi:10.1016/j.smim.2021.171508Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19. Sci Immunol. 2020 Sep 17;5(51):eabd6197. doi: 10.1126/sciimmunol.abd6197. PMID: 32943497; PMCID: PMC7857390 https://btswinter2021.online-event.co/page/bts-winter-conference-2021-6 > BTS Plenary Scientific 18https://btswinter2021.online-event.co/page/bts-winter-conference-2021-6 > BTS Plenary Scientific 19https://btswinter2021.online-event.co/page/bts-winter-conference-2021-6 > BTS Plenary Scientific 20Autoantigens – new territory https://www.imperial.ac.uk/news/232214/expert-optimistic-about-possibility-tests-long/22Clotting in COVID Blood (2020) 136 (Supplement 1): 27. 23 https://doi.org/10.1182/blood-2020-138851Post-COVID Coagulopathy? i 4 r 1 3 T M A 2 : g ( 1 F V 0 ma m a nr nr tb et Te T https://doi.org/10.1186/s12933-021-01359-7 doi: 10.1182/bloodadvances.2021006944[Epub ahead of print]Mitochondrial dysfunction? 25Ciliogenesis disruption 26Decreased size and deformability of erythrocytes of hospitalized COVID-19 patients. Typical scatter plot of erythrocyte deformation versus cell size (cross-sectional area) of a healthy blood donor with no known viral infection (A) compared with a patient 4 months after undergoing COVID-19 (B) and a patient with COVID-19 in an intensive care unit (C) is given. The erythrocytes shown in (D) are representative images of cells in the clusters marked by corresponding numbers in the scatter plot. (E) Kernel density estimate plots demonstrating the differences in cell size and deformation between the three donors (A– C). The comparison of median values of deformation (F) and SD of deformation (G) between the control group of blood donors (n = 24), recovered patients (n = 14), and patients hospita∗ized with∗∗OVID-19 (∗∗∗ 17) is shown. Statistical comparisons were done using Kruskal-Wallis test with Dunn’s post hoc test; p < 0.05, p< 0.01, p< 0.001. Kubánková,Markétaet al.“Physicalphenotypeof blood cellsis altered in COVID-19.”7 Biophysicaljournal vol.120,14(2021):2838-2847.doi:10.1016/j.bpj.2021.05.025You are here 2829Respiratory Red Flags 30Trajectories Expected Recovery Stuck / Fluctuating BoomerangCritical illness at home 32If you listen to your patient they are telling you the diagnosis William Osler 1849-1919 33TimothyJBarreiro,ChristianGhattasand CherryAnn Valino RespiratoryCareSeptember 2013,58(9) e107-e110;DOI: https://doi.org/10.4187/respcare.02231 3435Thank-you... ▪ Rebecca Gore ▪ Helen Davies ▪ Dr Ewen Brennan ▪ Dr Akshitha Devaraj ▪ Dr Anna Kessler ▪ Dr Harry Abrahams ▪ Charlotte Joo ▪ Dr Christian Hasford ▪ Florence Mutesva ▪ Dr Nithya Prasannan 36