Thread by @arlinelyons

Settling in to watch the @royalsociety 2-day event on COVID-19. Dame Linda Partridge starts with thanks to everyone involved in fighting the pandemic and scientific advances. #royalsociety #COVID19

"We can always do better" - Prof David Navarro on integrating context during the pandemic. "We need a story to make groups everywhere to appreciate what this pandemic means and their place in it." And that story is not easy to find. #royalsociety #COVID19

Prof David Navarro: the virus is the problem, people are the solution. Longer term illness is a huge potential threat, no-one should take infection lightly. The poorer you are the worse the impact of illness. #royalsociety #COVID19

Prof David Navarro: make sure measures to control COVID-19 are agreed by all, as a partnership, not imposed. What is agreed against COVID-19 can also work against other diseases. Leaders must not denigrate those who choose to adopt protective measures. #royalsociety #COVID19

Prof David Navarro: use vaccination to create an immunological shield for those at high risk, get story on vaccination right, emphasise protection of others. #royalsociety #COVID19

Surges seem to come every 4 months, patterns still not understood. Hospitals, services, employers need to prepare. Stopping people moving out of areas with surges is key, to prevent new surges spiralling out from the first location. #royalsociety #COVID19

Prof David Navarro: systems are key, but need to cut across differences in society to make them work. #royalsociety #COVID19

Prof David Navarro: WHO is permanently underfunded, constantly asking for more funding, has to balance demands of richer and poorer nations, especially as richer nations finance operations such as COVAX and COVID tools accelerator. #royalsociety #covid19

Sir John Irving Bell follows with an overview of the science of COVID. Pace of scientific progress, getting data, getting funding all massively accelerated. COVID was a surprise but should not have been, many "near misses" #royalsociety #COVID19

Sir John Irving Bell - complacency has developed around infectious disease, wrongly seen by some as a solved problem. Failure to learn from previous pandemics, good response for vaccines and clinical trials but not other areas. #royalsociety #COVID19

Sir John Irving Bell - regulatory innovation in the UK was hugely helpful. Response to COVID had to and did cross many scientific areas. Support from life science industry also key. Data from NHS excellent resource when available. #royalsociety #COVID19

Sir John Irving Bell - pandemic preparedness and public health capacity were poor. Poor communication with politicians, inconsistent scientific advice, scientific opportunism. #royalsociety #COVID19

Sir John Irving Bell - ugly aspects were scientific and medical nationalism, failure to provide rapid access to innovations in developing countries, profiteering in treatment and PPE spaces, failure to learn and prepare for next pandemic. #royalsociety #COVID19

Sir John Irving Bell - excellent surveying by UK Office of National Statistics and REACT study. 400 potential vaccines, 7 succeeded, impact limited by manufacturer, hesitancy, but strong protection against severe disease, mortality. #royalsociety #COVID19

Sir John Irving Bell - however we can see now that existing vaccines do not give lasting protection, may need reformulation. AZ vaccine easier to distribute, many manufacturing sites, dominant type in COVAX, used in many high-risk populations. #royalsociety #COVID19

Sir John Irving Bell - lucky that SARS-CoV-2 was susceptible to immunological response generated by vaccination. Need better protection against transmission, but overall vaccines have been a great success. #royalsociety #COVID19

Sir John Irving Bell - therapeutics in last flu pandemic failed to complete, lesson not learned in this pandemic except in RECOVERY trial. Now have paxlovid, could have been available earlier with less focus on vaccines, potential for resistance. #royalsociety #COVID19

Sir John Irving Bell - antibodies proven as effective modality for treatment. Testing in the UK was also a success. Lateral flow tests also proven to work reliably, sensitivity. Genomics/sequencing also great success. #royalsociety #COVID19

Sir John Irving Bell - need faster sharing of genomic analysis data for identification of variants, new project with Oracle. Immunological understanding of infection also key. #royalsociety #COVID19

Sir John Irving Bell - building back capacity involves testing, tools, antivirals, also capacity of health systems, also a financial question seen the damage to the economy. #royalsociety #COVID19

Sir John Irving Bell - self-use testing also key, removed bottleneck of lab testing, made it faster and scalable. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - mRNA vaccine technology excellent for developing vaccines [personal comment, scope and positioning of lecture very different from first two] #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - non-coding parts of vaccine are cell-specific, targeting dendritic cells, also needs formulation of lipids to transport mRNA. Technology developed out of project for individualised cancer vaccines. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - had to modify mRNA to improve its half-life and potency. Found modification of mRNA backbone that increased translation and much greater immune response. Other approach reduces immune response to synthetic mRNA. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - injection into a lymph node was found to be highly effective due to lymph node dendritic cells in cancer vaccines. This led to development of lipid nanoparticles that were easy to take up by immune cells/compartments. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - these developments provided blueprint for COVID vaccine, modified backbone, ability to administer intramuscularly and get strong immune response. System also allows rapid variation and manufacturing, on-demand production. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - development lead time for personalised cancer vaccines went from 3-5 months to 3-6 weeks, so development of vaccine against COVID spike protein could proceed rapidly. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - SARS-CoV-2 genetic sequence published 12 Jan 2020, stage 1/2 trial 23 April, phase 2/3 27 July, met all endpoints 18 Nov, authorisation UK 2 Dec, EU 21 Dec 2020. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - shows the vital nature of basic scientific research, needs proper funding, many technologies out there waiting to be brought to use, don't wait for another pandemic to make them a reality. #royalsociety #COVID19

Prof Özlem Tureci (BioNTech) - personalised treatment for cancer currently very expensive, hoping that advances in automation and miniaturisation will make it more affordable. #royalsociety #COVID19

Prof Edward Holmes - origin of SARS-CoV-2, first sequences revealed closeness to SARS and bat viruses. Novel furin cleavage site in spike protein, appears in other beta coronaviruses. Unclear if virus was present before identification in Wuhan Dec 2019. #royalsociety #COVID19

Prof Edward Holmes - close matches found in bats, pangolins, but not identical. Bats carrying these viruses also present around Wuhan. Cluster of cases around market in Wuhan are either linked epidemiologically or spatially close. #royalsociety #COVID19

Prof Edward Holmes - market technically a seafood market but also sold animals susceptible to these viruses, such as racoon dogs, that were implicated in SARS outbreak. Swabs of market after it was closed shows most positive results in area with wildlife. #royalsociety #COVID19

Prof Edward Holmes - could have originated in bats and gone through intermediate host, timing of outbreak just before mass movement around new year. Two lineages of SARS-CoV-2 seem to have jumped independently. #royalsociety #COVID19

Prof Edward Holmes - looking at animal viromes in China and threat posed by wildlife markets, animals carry viruses that can cross over to humans. These spillovers are common, e.g. swine flu 2005-09. Destruction of natural habitat brings more contact. #royalsociety #COVID19

Prof Wendy Barclay on variants and evolution - advisor to SAGE and the public. Successive variants since Dec 2020 have driven development of the pandemic. #royalsociety #COVID19

Prof Wendy Barclay - early variants became more infectious and able to evade antibodies. Omicron poorly neutralised by antibodies from vaccination (against original strain) due to antigenic drift). Protection against Omicron is lower and fades faster. #royalsociety #COVID19

Prof Wendy Barclay - will future variants evade immune response AND cause severe disease? SARS-CoV-2 can be transmitted early in infection, before visible symptoms. Furin cleavage site is key to infectiousness. #royalsociety #COVID19

Prof Wendy Barclay - original furin cleavage site was suboptimal, evolved and was optimised through emerging variants. Delta caused cells to fuse, causing severe lung damage, Omicron does not do this. #royalsociety #COVID19

Prof Wendy Barclay - Omicron replicates rapidly in the nose, but is less successful in the deep lung, due to genetic changes in the spike protein. Omicron has 35 mutations in spike gene alone, in both antigenic and functional areas. #royalsociety #COVID19

Prof Wendy Barclay - Omicron spike is best so far at binding to human ACE-2 receptor. Omicron mutations stabilise the spike, slow fusion of viral particle with the cell, allowing it to enter via endosomes, a second path of entry, more cells susceptible. #royalsociety #COVID19

Prof Wendy Barclay - however, endosome route blocked in the lung by endosome restriction factors, making Omicron less successful in the lungs. Effective drugs differ by cell entry route. #royalsociety #COVID19

Prof Wendy Barclay - risk that another variant will emerge that is as transmissible as Omicron but causes severe disease similar to Delta. Unclear what is driving the mutations stabilising the spike protein. #royalsociety #COVID19

Prof Wendy Barclay - tendency of Omicron to reproduce in the nose instead of the lower respiratory tract may affect immune response. #royalsociety #COVID19

Prof Stanley Perlman - immune response to COVID-19 and other coronaviruses, learnings from previous viruses. In mice with no B or T cell response, many white matter cells infected but not damaged. Immune response is what causes damage. #royalsociety #COVID19

Prof Stanley Perlman - balance and timing of innate and adaptive immunity is key. Peak titer for SARS-CoV-2 is days 1-3, interferon production lags, leads to more severe disease, worse outcome. #royalsociety #COVID19

Prof Stanley Perlman - hard to tell when to administer interferon and to who, no good biomarkers. Studies show that immune response wanes over time for all coronaviruses. #royalsociety #COVID19

Prof Stanley Perlman - severe disease tends to lead to stronger response from antibodies, some T cells. Coronaviruses also have ways to evade the immune system. Memory B, T cells provide prolonged protection, but seem insufficient to prevent reinfection. #royalsociety #COVID19

Prof Stanley Perlman - unresolved loss of taste/smell may be precursor to neurodegenerative disease, e.g. Alzheimer's. Long COVID resembles chronic fatigue syndrome, also poorly understood. #royalsociety #COVID19

Prof Stanley Perlman - T cell response works for all variants, if T cell response is good enough don't need antibody response. T cell response differs across individuals due to different haplotypes. #royalsociety #COVID19

Prof Stanley Perlman - loss of taste/smell may be related to inflammation persisting after viral infection. Endothelialitis, affecting organs. #royalsociety #COVID19

Tuning back in to the Royal Society Science of COVID event, just at the end of the vaccines and new modalities session. Hopefully I can catch up with those talks later.

On to diagnostics, with Prof Chris Molloy, CEO, Medicines Discovery Catapult. #royalsociety #COVID19

Prof Chris Molloy - starts by thanking the thousands of people who made the testing system possible, the value of breaking out of silos, and the need to stay out of them to avoid going backwards. #royalsociety #COVID19

Prof Chris Molloy - there was no equipment, people, facilities. Highly distributed systems require the logistics that can support them. Industry supplied scaling, rigour, academia contributed expertise. So many people volunteering themselves, anything. #royalsociety #COVID19

Prof Chris Molloy - a donated fume hood with "Good luck" written on it. #royalsociety #COVID19

Prof Chris Molloy - nothing was "winging it", it was raising existing capacity to an industrial scale, with all the proper safeguards. #royalsociety #COVID19

Prof Chris Molloy - crying in front of members of staff generally not a good idea, but I did it a lot. It was the only emotion left. #royalsociety #COVID19

Prof Chris Molloy - educating the public also important, links between swab and result, why behaviour needs to change. Making the extraordinary, complex idea visible. #royalsociety #COVID19

Prof Chris Molloy - "territorial army" for fast response as and when needed. #royalsociety #COVID19

Prof Sharon Peacock - actionable information from sequenced genomes during the pandemic. History, scale, data, adding value, future research. #royalsociety #COVID19

Prof Sharon Peacock - existing sequencing projects meant UK had capability for large scale sequencing, project was funded quickly, project generated actionable results very quickly. #royalsociety #COVID19

Prof Sharon Peacock - sequencing network was large enough to provide data for public health guidance, vaccine development, variant tracking. Also tracked where imported waves were coming from. #royalsociety #COVID19

Prof Sharon Peacock - after the service was running, focused on becoming faster, cheaper, increasing scale, transitioned out of public health network. Developing training courses to improve sequencing skills in other countries. #royalsociety #COVID19

Prof Sharon Peacock - now have over 2 million viral genomes. Merging this information from host genetics, medical records, to determine factors for susceptibility to COVID. #royalsociety #COVID19

Prof Sharon Peacock - with unlimited funding, need surge capacity on a standing basis. Also should use sequencing more liberally for many other areas. #royalsociety #COVID19

Dr Ruth March - AstraZeneca, diagnostic testing for asymptomatic and early disease. Normally works on companion diagnostics for specific drugs. #royalsociety #COVID19

Dr Ruth March - reason for developing diagnostics including ensuring minimum staff absences to ensure essential drug manufacturing could be continued, needed contact tracing and to keep asymptomatic staff out of the workplace. #royalsociety #COVID19

Dr Ruth March - asked to do something that normally takes 18 months in 18 days. As mentioned, the bottleneck was not in the science/technology, more in the willingness. Had to keep their testing system separate from national healthcare. #royalsociety #COVID19

Dr Ruth March - issues with staff unfamiliarity with technology, swabbing, logistics, refrigeration, testing, contacting positive cases and app notifying of negative test, ideally within 24 hours. But take-up for app was just 30%. #royalsociety #COVID19

Dr Ruth March - used anonymous surveys/interviews to find out why. Resistance to nasopharyngeal swabs, switched to saliva. Adapting technology, simplifying, weekly updates, using rapid antigen tests, greater sustainability, family pooled assessments. #royalsociety #COVID19

Dr Ruth March - adoption rate increased 5-fold, no lab or production line closed during the pandemic. Positive rates in the company 10-fold lower than outside. Testing was made quicker, faster, more accessible, more familiar. #royalsociety #COVID19

Dr Ruth March - potential to extend these advantages to other conditions, e.g. cancer. When cancer detected by imaging, tumor burden is too high for cure. Better detection of asymptomatic/presymptomatic disease could enable long-term survival, even cure. #royalsociety #COVID19

Dr Ruth March - precision diagnostics also enable targeted treatment. Aim to use home or local doctor testing to monitor cancer as a chronic disease. Issues include inequality in access. Science is ready, but practical barriers not taken into account. #royalsociety #COVID19

Dr Ruth March - how to match learning from the pandemic with real world problems? Issues with regulatory, reimbursement, investment, coordination, patient-centric. #royalsociety #COVID19

Closing keynote for day 1, Prof Sir Chris Whitty #royalsociety #COVID19

Prof Sir Chris Whitty - how to translate science into policy and practice. Triangle of difficulty of the intervention - size of positive health effect - strength of evidence. But in the emergency state of the pandemic, evidence not there yet. #royalsociety #COVID19

Prof Sir Chris Whitty - used established science, limited data from China, Korea,Italy, had to give advice that had a good chance of being wrong. Later developed testing and surveillance, repurposed existing tools. Finally developed COVID-specific tools. #royalsociety #COVID19

Prof Sir Chris Whitty - interventions have gone from social to medical, as disease is better understood. Quarantine, closing high risk occupations, isolation of the sick predate germ theory. Any new pathogen will require social intervention at first. #royalsociety #COVID19

Prof Sir Chris Whitty - policy questions can only be answered by a combination of many basic and applied sciences, plus social and behavioural sciences, e.g. anthropology. But scientists are not trained to work across disciplines, not prized. #royalsociety #COVID19

Prof Sir Chris Whitty - scientists could only give difficult options to governments, except vaccines. Interventions against COVID also impacted other areas of public health. SAGE tried to synthesise views from different disciplines, communicate uncertainty #royalsociety #COVID19

Prof Sir Chris Whitty - parallel strand of scientific insight for technical disciplines, e.g. what drugs to use. Needed to speed up research -> guidelines, which happened, but this carries a risk. #royalsociety #COVID19

Prof Sir Chris Whitty - UK is big enough to produce significant results, but not too big. Also benefited from ongoing research on known pathogens, ability to stop NHS using some drugs unless part of a trial. #royalsociety #COVID19

Prof Sir Chris Whitty - can't keep borrowing infrastructure from other parts of the scientific system taken over by COVID. But not over yet even with all these developments. #royalsociety #COVID19

That's it for day 1. Absolutely fascinating and at times emotional, focused on research and technology but also very much on people - scientists and the public.

Steve Rees of AstraZeneca points out that many tools key to the response to COVID-19 did not exist 20 years ago, some even 5 years ago, illustrating the need for investment in life science. #royalsociety #COVID19