Covid-19 What the UK Got Wrong

Lockdown and border closures
(BBC News Was the scientific evidence for lockdown flawed? 19 Nov. 2020.)

23 Jan. 2020: A woman unknowingly infected with Covid-19 flew to the UK from Wuhan and passed through the airport undetected. Eight days later she and a family member became the first confirmed UK cases, followed by many others who spread the virus in February and March when returning from China and from holidays in Italy, France and Spain. It is now thought that there were 1,500 UK cases during that period, so the UK was hit hard. Closing borders earlier could have reduced UK infections.

Modellers used information about the early cases held in the First Few Hundred (FF100) database to assess how the virus might spread, but FF100 was missing basic epidemiological information. Data was needed not only on where the virus was coming from, but also on who was worst affected.

 Mid-February. Evidence from China showed older people were especially at risk, so modellers advised that 'cocooning' would reduce deaths. Unfortunately models did not reflect how care homes actually work, or the serious risk from agency staff working in multiple homes.

Early March. Due to lack of accurate date, plans were still based on a fairly slow growing pandemic with a peak of cases in 12 to 14 weeks. One scientist thought official figures (913 cases) were wrong and called for an immediate lockdown; experts now estimate there were 75,000. Investigation focused on cases in intensive care units, as there be very many more who had a mild symptoms. The prediction was for c.100,000 new cases each day by mid-March, followed about a week later by 20,000 people each day needing hospital treatment. It was also realized that the NHS data  was out of date, in many cases up to a week old.

17 March. First restriction imposed - stopping non-essential contact with others, unnecessary travel, working from home and avoiding pubs, clubs, theatres and other social venues. It was thought that without this cases could double every five or six days. Data from Italy indicated that the virus was spreading at nearly twice the speed that had been thought - with the NHS potentially just days away from being swamped.

So should we have acted earlier? Modelling now suggests that if lockdown had been imposed a week earlier, we may have avoided around half the number of deaths. Relying only on modelling and using that alone to drive the response it turns out was not the right thing to do.

Test and Trace
(BBC News Coronavirus: inside test-and-trace - how the 'world-beater' went wrong. 20 Nov. 2020)

Just half of close contacts reported to England's Test and Trace are being reached in some areas. As attempts continue to get it back on track, it is still struggling with the legacy of decisions made at the outset.

NHS Test and Trace is not one whole service nor is it part of the NHS. It is a complex web of several programmes that have been bolted together quickly. Private firms play a key role, so some of the local expertise available in the NHS, universities and councils has been bypassed.

Private contractors overpromised what they could do (e.g. saying they could build 200 testing machines when they did not even have a prototype).

17 March. No-one from NHS labs was at a key government meeting with private firms (e.g. health-technology firms Randox and ThermoFisher) where it was decided to set up large, centralised labs outside any existing healthcare or research structures. This network of six mega-labs (Lighthouse labs) process the bulk of the tests across the UK. Testing sites were set up by financial and tech services company Deloitte. The contact centre is run by Sitel, and the 18,000 contact tracers are mostly employed by outsourcing company Serco - but does include c. 3,000 clinicians, some from the NHS. (This applies to England only, the rest of the UK has their own arrangements.) Contracts were awarded very quickly and many had no penalty clauses for poor performance.

Nov. 2020. England now has a large testing capacity, which can process more than 500,000 virus tests a day (up from 2,000 per day). But the system still struggles to get results quickly, since many samples were sent long distances for processing. If the approach had remained local by using existing networks of hospital, university and Public Health England, turn around would be much quicker.

Other companies were selling testing machines to NHS labs which did testing for hospitals - but the kits and chemicals needed for those machines were in short supply and being bought by the privately-owned Lighthouse labs.

The later move to more local contact tracing by councils was undermined by IT problems, leading to a reliance on spreadsheets and delays getting contact details.

Testing Targets

The government focused on hitting very high testing targets, but less so on who should get tests and why. People working in hospitals were not screened unless they had symptoms, despite evidence showing significant transmission there. However despite being 'effectively discouraged' to do so, some labs set up regular screening for healthcare staff. (E.g. The Univ. of Cambridge research lab partnered with nearby Addenbrooke's to offer this, and by the end of June had screened more than 10,000 hospital staff to detect asymptomatic carriers.)

Sept. 2020. Just as the second wave was starting, tests became near-impossible to access, due to people returning from holidays and children going back to school. The Lighthouse labs struggled as they were unable to forecast the sample numbers which varied wildly from day to day - so having enough staff to process 10,000 samples and only receiving 2,000 or having more than expected. As those involved in setting up the labs didn't always have experience with viruses, procedures needed constant tweaking, and there were issues with recruitment and training.

Tracing

Of the c. 18,000 contact tracers hired, only about 3,000 had a clinical background. While those who get the best results are good communicators, tracers were told to follow heavily scripted cues. With no room for discretion, call handlers had to try to make individual calls to every member of a household and go through the same forms. Unfortunately contact tracers often get abuse because of this. The government now says the system will be changed.

Performance is not at the right level. Advisors say 80% of those who test positive should be reached and close contact details obtained, and 80% of those contacts should be reached and asked to isolate. In some areas only half of contacts are reached. A change to greater local involvement was announced in August but funding was only announced in late October. 

And local schemes still face problems due to the centralised system. Delays getting cases passed down from the national team. Cases passed on are missing key contact information or are duplicates of cases already traced. Lack of access to NHS Test and Trace central IT system means councils are forced to record the information they collect on spreadsheets. Councils are only allowed to trace the infected case, so cannot deal with family members, even if they are on the door-step.

While money was allocated to find individuals, there was little thought on how to support people asked to isolate. The number isolating after a positive test or as a close contact is not routinely measured. Some have argued that the isolation period is too long - some other countries only require 7 days. Financial support for those isolating is limited to statutory sick pay; a one-off £500 payment for those on benefits is not available if you've been told to isolate via the app. The consequence is that people are less cooperative. 

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NHS Facts and Claims During Elections

During campaigning for elections, politicians make claims about their performance, the opposition performance and how they will make things better. So here are a few from recent elections from Boris Johnson and Jeremy Corbyn.

BJ: Claim: We'll get 40 new hospitals. False: Tory plans for £2.7 billion for 6 hospitals over 5 years, plus £100 million for 34 hospitals to start developing plans.

JC: Claim: Cancer treatment times have risen. Correct: First treatment within 62 days of GP referral is down from 86% in 2010 to 79% now.

BJ: Claim: Cancer survival rates have increased since 2010. Correct but not due to Tories. Surviving one year after diagnosis improved from 2010 (70%) to 2016 (73%). The same increase of 3% happened between 2004 and 2010.

JC: Claim: NHS has had the largest squeeze in its history (i.e. since 1949). Correct: The NHS budget has never fallen under any government, with an average rise of 3.6% p.a. But between 2010 and 2018 it rose just 1.3% on average. In 2018 announced an annual increase over the next five years of 3.4%.

BJ: Claim: There are 17,000 more NHS doctors and nurses than in 2010. Correct.

JC: Claim: There are currently 43,000 nursing vacancies. The UK needs around 60,000 more nurses to cope with an increasingly aged population. Correct.

BJ: Claim: Missed NHS targets in Wales (Labour led government.) Correct. (JC stated that the problems in Wales stem from Conservative cuts to the Welsh budget, and in real terms spending won't return to 2010 levels until around 2023.)
JC: Claim: Missed NHS targets in England (Conservative led government.) Correct.
Both parties cherry picked which figures to publicise. The target of 95% of arrivals in A&E being seen within four hours has not been met in England since 2015, and in Wales since 2008.

Tory Pledge: Train 500 more GPs per year. (Their previous pledge was to recruit an extra 5,000! In fact there was an increase of just 272 between 2015 and 2018. and the 2019 pledge of 500 was not met in 2020.)

JC: Claim: Regarding Brexit and trade deals - fears over a Trump deal wanting access to the NHS.
BJ: Claim: Said the NHS would be protected. (My note: Why should we believe someone who has lied in the past?)

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Six Types of Covid-19

Symptoms of  Covid-19 vary enormously. Initially thought to be simply a respiratory disease, it is now known to be able to affect all body systems, and age, gender, ethnic background and existing medical conditions will all affect how an individual is affected. A team from the Covid Symptom Study have now split the disease into six types.

Symptoms tend to appear between two and 14 days after infection.

1. Flu-like symptoms but no fever. Headache, loss of smell, cough, sore throat and aches and pains, but no fever. Around 1.5% of this group go on to require breathing support in hospital.

2. Flu-like symptoms with fever. Similar to group 1, plus a loss of appetite and fever.

3. Gastrointestinal. Diarrhoea alongside loss of smell and appetite, headache, sore throat and chest pain. Typically, no cough.

4. Fatigue. This cluster is considered more severe than the previous three, as 8.6% require breathing support. Fatigue accompanies headache, loss of smell, cough, chest pain and fever.

5. Confusion. Another severe category. People experience confusion in addition to symptoms listed in cluster 4. Around 10% will require breathing support.

6. Abdominal and respiratory. The most severe cluster, since almost half will require hospitalisation, and around a fifth will need breathing support. Symptoms include headache, fever, loss of smell and appetite, cough, sore throat and chest pain, along with shortness of breath, diarrhoea and abdominal pain, muscle pain, confusion and fatigue.

Some people contract Covid-19 but either show no symptoms, or very mild symptoms that cause no real problems. 

Children and Teens

Children seem to be affected differently to adults. A study at Queen's University Belfast suggests that the most predictive symptom is diarrhoea and vomiting, along with other of the possible symptoms. The current UK testing strategy would have missed 24% of symptomatic children, but including diarrhoea and vomiting would mean that 97% would have been detected.

The virus binds to ACE2 receptors. It is thought that children may express fewer of these receptors in the nose and throat.

Teenagers are more likely to report loss of taste and smell. Research currently suggests that symptoms for teenagers are closer to adult symptoms, though mostly are mild.

Source: Article Covid-19 symptoms rethink in New Scientist, 10 Oct. 2020. 

Vaccine Update

Several vaccines have been developed and have been undergoing trials for safety and effectiveness in order that they can be licensed. Here is the latest information and I will continue to update this post.

Vaccines are usually cultured in animal cells (e.g. chicken eggs for flu vaccines). Work is ongoing to develop plant based methods.

Vaccine timings. All currently (Feb. 2021) approved Covid-19 vaccines require two doses. In trials these were 3 weeks apart. Early Jan. 2021. As immunity develops over time, the UK extended the time between first and 'booster' doses to 12 weeks. 13 Feb. 2021. France has decided to give only one 'booster' dose of vaccine to anyone who has had the virus, and therefore already has some antibodies.

I can't have a vaccine, as my immune system doesn't function as it should due to an immune deficiency or because taking immune-suppressing drugs for another illness (e.g. cancer). A possible alternative to a vaccine is entering final stage trials, with first results expected in spring 2021. Developed by AstraZeneca, this uses Covid-19 antibodies from a single Covid patient in the US. The hope is that it will provide protection for at least six months, and possibly a year. However, the therapy is significantly more expensive than vaccination and difficult to produce at scale, so unlikely to be used for the wider population. AstraZeneca has also suggested it could possibly be used in care home settings to protect residents if a case is identified. While vaccines take time to build immunity, this should work immediately, so could be used as a preventative measure.

I have severe allergic reactions and carry an Epipen. People with known severe allergic reactions can react to any vaccine (including flu vaccinations) and are advised not to have a Covid-19 vaccine. If they do suffer a reaction they are treated with drugs such as steroids or adrenaline.

Common misconceptions about vaccine testing. Because of the speed with which vaccines were developed, some people are concerned that not enough testing was carried out. This is not the case. All normal testing was carried out as it would have been in non-pandemic times. However, researchers were able to move from one phase to the next without having to spend months or years to get funding for the next stage trials. However, rare side effects (of any vaccines or other drug treatments) are not always encountered in trials and are only reported when being used for prevention or treatment in many times larger numbers.

Side effects

• Many vaccinations do cause minor side effects, which usually quickly go away on their own. Typically there is often some soreness at the vaccination site. The most common other side effects are mild fever, chills, feeling tired and joint and muscle aches. 
• Women may sometimes experience a delayed period. This reverts to normal after one affected cycle. This side effect is not confined to Covid-19 vaccines, and can happen with other vaccines (such as flu vaccines) as well.

Serious side effects are rare

• Serious side effects are extremely rare, affecting 1 or 2 people in 1 million.
• Although vaccines are tested in large scale trials before being approved for general use, it is possible for rare side effects to only emerge once much larger numbers of people receive a vaccination. 
• As some instances are extremely rare occurrences not related to a vaccine, researchers will check to see if there is a link, and if there is, what is causing it. 
• They will compare the reported cases with the normal incidence in a population. For example, blood clots. While it now appears there may be 1 in 250,000 people who suffer this with the Astra Zeneca vaccine, far more will get this from other causes: 1 in 2,000 women develop blood clots from taking the combined oral contraceptive pill, and 1 in 1,000 people from air travel. 
• The possible Astra-Zeneca blood cases review did not compare the number of vaccinated people with this syndrome with the rate in unvaccinated people. Two of the reported cases had pre-existing blood clotting disorders, while for the other cases it was not stated whether they had recently had a Covid-19 infection, which itself can cause increased blood clots.
• Most of the cases occurred in women under 55, a group that already has a higher rate of blood clots because the contraceptive pill raises the risk of them.
• Being infected with Covid-19 also carries far more risks of blood clots developing. Thus 7.8% of cases develop pulmonary embolism, 11.2% deep vein thrombosis, 1.6% strokes and c. 30% thrombocytopenia. If admitted to Intensive Care Units, c. 23% of cases have venous thrombolism.

Vaccines approved for use in UK: Oxford Univ./AstraZeneca # Pfizer/BionTech # Moderna #

Oxford.Univ and Astra Zeneca (approved 30 Dec. 2020) UK has ordered 100 million doses. Vaccinations begun 4 Jan. 2021.

• Type: Uses a harmless virus that infects chimpanzees.
• Doses: Two doses a month apart. (Overall protection from both dosage trials is 70%).
• Protection (1): Full dose followed by full dose. Trial data indicates 62% of trial participants appear to be protected. Analysis also suggests a reduction in numbers being infected without showing symptoms.
• Protection (2): Half dose followed by full dose. Two weeks after the second dose, more than 90% of trial participants appear to be protected. 
• Protection (3): Why is the low dose better? (A) The immune system may reject the vaccine, which is built around a common cold virus, if it is given in too big a dose. (B) A low shot then a high shot may be a better mimic of a coronavirus infection and lead to a better immune response.
• UK and Overseas Trial: Phase 2 showed a strong immune result in adults in their 60s and 70s, based on 560 adult volunteers. Phase 3 in progress. No-one getting the vaccine developed severe Covid-19 or needed hospital treatment.
• US Trial: More than 32,000 volunteers, mostly in America, but also in Chile and Peru. The vaccine was 79% effective at stopping symptomatic Covid disease and 100% effective at preventing people from falling seriously ill. There were no safety issues regarding blood clots. The vaccine provided volunteers over 65 as much protection as younger age groups. Trial report March 2021.
• Side Effects: Apart from minor side effects (soreness at injection site, and mild headaches, fever and aches that clear up quickly) none were reported in trials. Early April 2021: a small number of cases of rare blood clots and low platelet levels were reported. There were 79 cases and 19 deaths among more than 20 million vaccinations in the UK. This equates to 1 case per 250,000 people (0.004%) and 1 death per million. The EU investigated 62 cases of cerebral venous thrombosis and 24 cases of sphlanchnic vein thrombosis, of which 18 were fatal from around 25 million vaccinations in the EU and UK. It is thought that a condition similar to heparin induced throbocytopenia occurs. Both UK and EU regulators deemed the vaccine safe to continue using but recommended that where possible people under 30 should be offered a different vaccine. 
• Notes (1): Can be stored at fridge temperature, unlike the Pfizer and Moderna vaccines, enabling it to be distributed world wide. 
• Notes (2): The Oxford technology is more established, so the vaccine is easier to mass produce cheaply. Costs around £3 per shot, less than Pfizer (around £15) or Moderna (£25) vaccines.
• Notes (3): A batch of trial vaccine was more concentrated. To avoid wastage, and with regulator approval, volunteers were given smaller amounts for their first dose and a full second dose. Results indicate that this gave better protection. 

24 Jan. 2021: Oxford University potential new vaccine (RBD-SpyVLP). Early animal studies show it could be effective in lower doses, making it easier to make in large quantities and be used in conjunction with other vaccines. This type of vaccine is not a competitor for the first wave of vaccines, it is hoped that it could be a standalone vaccine or a booster for those with a different Covid vaccine. Tests also show it is highly resilient, stable at room temperature and can be freeze dried without damage. These properties mean it would reduce dependence on cold chain transport and storage and help with global distribution. (Source The I newspaper 24/01/2021).

Pfizer and BioNTech: Licenced for use in UK early Dec. 2020. First order of 10 million doses started to arrive in early December; a further 30 million doses already ordered. 

• First vaccinations: 8th Dec. 2020. Over 80 age group and hospital and health care workers.
• Contraindications: Anyone with a history of severe allergic reactions. Reactions like this are uncommon but not unknown with various vaccines, including flu vaccines.
• Type: RNA - virus genetic code (uses part of the Covid-19 genetic code)
• Doses: Two doses, three weeks apart.
• Protection: Trial data (based on the first 170 volunteers to develop symptoms) indicates that 95% protection is achieved seven days after the second dose. There is also emerging evidence that it protects against severe Covid, but this is based on only 10 cases.
• Trial: 42% of all participants are from diverse ethnic backgrounds and 41% are aged between 56 and 85 years old.
• Side effects: Myocarditis (heart inflammation) can occur after infection with Covid-19 (typically within three months of catching it), with males 12-17 most likely to do so; rate of this complication is c.450 cases per million infections. Myocarditis following a second dose of Pfizer vaccine is much less common with just 67 cases per million. Mild cases are usually treated with anti-inflammatory drugs such as ibuprofen, with most people recovering within a few months. 
• Notes: There are massive manufacturing and logistical challenges as the vaccine has to be kept in ultra-cold storage at below minus 80C.

Moderna: Licenced for use in UK 8th Jan. 2021. Each person needs two doses. Not one of the six the UK initially ordered; 17m now on order, should be available spring 2021. 

• Type: RNA - virus genetic code
• Doses: Two doses, four weeks apart.
• Protection: Trial data (based on the first 95 to develop symptoms) indicates 94.5% is achieved after the second dose, appears to be effective in older age groups.
• Notes: The vaccine remains stable at minus 20C for up to six months and can be stored in a standard fridge for up to one month.

Novovax: The UK has secured 60m doses, which will be made in Stockton-on-Tees in NE England. If approved, supplies are expected to be available in the second half of 2020.

• Type: Uses recombinant nanoparticle technology to grow harmless copies of the virus spike protein, teaching the body's immune system to recognise and fight the pandemic virus.
• Doses: Two doses three weeks apart.
• Protection: Trial data indicates 89.3% effective in large-scale UK trials, and that it is effective against the faster-spreading variant present in the UK, and the South African variant.
• Notes: 

Russia Sputnik V: Registered for emergency use in August 2020, although had only been tested on a few dozen people. December 2020: doctors, teachers and social workers are being offered Sputnik V in a mass inoculation campaign ordered by President Putin. Still in trial, so some Russians are wary of receiving it yet.

• Type: Uses a harmless virus that infects chimpanzees. Comprises two entirely different injections, using different 'vectors' or carriers each time. This puts extra pressure on producers as the first component is the most stable but the second needs strict temperature controls.
• Trials: Still in midst of safety and effectiveness trials.
• Data: Reported to be 92% effective.
• Notes: Must be stored at -18 C at least in its liquid form. A planned powder version is not yet being made in large amounts.

China CoronaVac: Produced by biopharmaceutical company Sinovac. Although already in use and being shipped to some Asian countries, it has yet to finish late-stage trials.

• Type: An inactivated vaccine, using killed viral particles to expose the immune system to the virus without risking serious disease response. It is a more traditional method that is used in many vaccines like rabies.
• Doses: Two are required.
• Trials: Stage 1 and 2 trials completed, stage 3 still in progress. Jan. 2021: trials in Brazil found it only 50.4% effective.
• Notes: Can be stored in a standard refrigerator at 2-8 C. Therefore like the Oxford-AstraZeneca vaccine is more useful to developing countries where ultra low temperature storage is an issue.

In development

• Canadian company Medicago has produced a Covid-19 vaccine. (Jan. 2021. No details on this.)
• Janssen (trial volunteers being recruited). Type: Uses a modified common cold virus.Trial: 6,000 volunteers to be recruited in the UK, as part of 30,000 worldwide to assess whether two doses are more effective.
• Codagenix, US: Single does nasal spray using a modified synthesised version of the virus to provoke an immune response. Feb. 2021: in Phase 1 trials.
• Valneva, France: Whole inactivated virus two-shot vaccine. This type of vaccine can be given to vulnerable populations at risk of allergic reactions. Feb.2021: in Phase 1 and 2 trials, with plans for testing on children.
• Inovio, US: Synthesised DNA version of Covid-19 spike inserted into DNA plasmids. Two-shot vaccine blasted into skin using re-usable 'gun'. DNA Vaccines don't require frozen storage, have a one-year shelf life at room temperature and up to five years in a refrigerator. Feb. 2021: in Phase 2 trials.
• CureVac, Germany. Uses mRNA built from naturally occurring nucleotides stabilised to induce a strong innate immune response. A portable mRNA printer is also being developed to rapidly manufacture doses where vaccine is needed and used to produce on demand. Feb.2021: in Phase 3 trials. (UK says it will buy 50m doses if approved.)
• Vaxart, US: In early stages of developing a vaccine in pill form that could be distributed by post. Weakened human adenovirus (Ad5) loaded with genes from the coronavirus for both spike and shell. Designed to break down in the small intestine. Feb.2021: Phase 1 study shows it elicits response from T-cells in bloodstream and antibodies in nasal lining but no antibodies in bloodstream. 
• CanSino Biologics, China: A vaccine similar to the Oxford/Astra-Zeneca one. Feb.2021: in Phase 3 trials, which include 30 children aged 6 and 12 given two shots.
• GCVI, global initiative: Vital part of spike protein grown in transgenic yeast and mixed with an adjuvant. This type of vaccine has a good track record, and is similar to a common hepatitis B vaccine. Such vaccines cost about $3 for two doses, and is likely to be suitable for children. Feb.2021: in Phase 2 trials in India. GCVI will seek emergency authorisation in India within months and is negotiating with manufacturers in Africa, Latin America and the Middle East.

Sources: Various.

Why People Use 'Um' and 'Uh' When Talking

If you listen to conversations, it is clear that we don't speak in beautifully formed sentences. Spontaneous speech is often vague and full of potential for confusion, not least because people generally come to a topic with different backgrounds and levels of knowledge.

The use of words such 'uh', 'um' and 'like' are often criticised, but it turns out that these filler words are actually essential for efficient communication, enabling two speakers to better understand each other. Without changing the meaning of a sentence, they help us co-ordinate conversations with minimal confusion. 

Uh and Um don't replace pauses in a speech, they announce them. The pauses after um are usually about twice as long as those after uh. This suggests that they signal something specific, managing the listener's expectations of what will come next. Pausing mid-sentence without an um or uh to signal a delay is very disconcerting.

Umming and uhing used to be thought to be a sign of deception, with truth tellers not having to come up with a convincing story. Unfortunately, the latest research indicates the opposite. Lots of umming and uhing  may signal someone is telling the truth, perhaps because they are making less of a conscious effort to present a front.

All these filler words rely on interpreting another  person's mind, which is a highly cognitive skill. It seems that 2 year old children don't respond to filler words but 3 year olds do, suggesting that our understanding of these signals develops along with other verbal and cognitive skills.

UH Using uh before a plot point in narrative seems to improve listeners subsequent recall, while replacing the uh with a cough reduced the recall. 

UM Prepares us to be surprised by something new or unfamiliar, a signal that something is changing in the conversation. 

HUH Provides essential feedback to speakers, allowing them to clarify a point before a mistake gets out of hand.

MMM Signals our intention to let the other speaker continue with their point.

LIKE Speakers of every language co-opt certain words to punctuate sentences in a way that seems gratuitious. In English, one such word is 'like', but its use may not be as random as it first seems. It may be that it acts as a form of emphasis, based on the participants' knowledge of each other. If you like a band, saying 'the concert was, like, 2 hours away' would mean the concert was worth the effort of a long drive. But saying 'the concert was, like, 2 hours away' if you hate driving, would mean that the distance was too far for you to be willing to go make the effort.

Source: Article Speak like, uh, a pro by David Robson, New Scientist 17 Oct. 2020