^{The Weekend Report – Issue 23}

By Matthew Fletcher, Nicola Oliver and John Roberts

COVID-19 Actuaries Response Group – Learn. Share. Educate. Influence.

COVID-19 is still one of the hottest topics for scientific papers and articles. The COVID‑19 Actuaries Response Group will provide you with a regular weekend update with a curated list of the key papers and articles that we’ve looked at recently.

Modelling

Study shows 47% antibody prevalence in Tokyo … but is it all it seems?

A startling paper describes how a survey of over 1,800 people in Tokyo has found an antibody prevalence approaching 50%. As might be expected this has attracted interest on social media, as it might suggest herd immunity could be more quickly achieved. A comprehensive critique on Twitter  observes many deficiencies in the methodology however, not least that the sample derives from just one employer (albeit from multiple sites).

New study from Tokyo measuring antibodies of asymptomatic workers from 1 company is claiming 47% of the pop. of Tokyo (14M) have developed antibodies to SARS-COV-2. Findings from the paper is already spreading in certain circles. Does it make sense? 1/n https://t.co/syMSCcK9gI pic.twitter.com/L9KUwpaQhv

— COVID Impact (@CovidSerology) September 24, 2020

In addition, the sample size was effectively just 615, the FDA regards the testing as unreliable (at least one country has banned that test kit’s use), and clustering and super-spreading effects are summarily discounted. Finally, the paper doesn’t acknowledge the contrast with the Japanese Ministry of Health’s own figures which are an order of magnitude lower.

At a time when there are many diametrically opposed views on the severity of the pandemic and how it should be managed, and with social media playing an ever-increasing role in influencing people’s attitudes and COVID-secure behaviours, this shows how important it is to look beyond the headlines, and investigate any claims made. Who do you believe?

Clinical and Medical News

Challenge trial

Several media outlets including the BBC are reporting that a challenge trial, in which healthy young volunteers are infected with the virus in order to test effectiveness of a vaccine, are a step closer. The trial, which could be a world leader, is likely to start in January, be held in London, and supported by the UK government.

The report notes that volunteers will be monitored round the clock in a clinical research facility, and the trial could be used to speed the selection of a vaccine from the current promising candidates.

Pre-existing immunity and T cells

The BMJ has published a short paper discussing the possibility that a much larger proportion of the population may have immunity to SARS-CoV-2, through the presence of T cells, than the number showing the presence of antibodies.

It notes several studies which have shown the presence of T cells displaying a degree of reactivity to the virus in those known not to have had any exposure to it, which may mean that immunity levels following the first wave are higher than we have otherwise predicted.

The paper goes on to discuss whether required herd immunity levels are overstated given the ways in which populations interact. In light of recent trends both in the UK and Sweden, cited as examples of recent stable low levels of infection, it’s debatable as to how valid the points made are in the context of managing the current situation.

The subject of T cells immunity is clearly an important one. We intend to cover the key points and the current state of research in a future bulletin.

International study on COVID-19 treatment

ISARIC has published a report  covering the treatment and outcomes of over 81,000 patients hospitalised with the virus. The report resembles the regular ICNARC reports on ICU treatment in the UK (which we have summarised via our Twitter account), but extends beyond ICU patients. Around 84% of the data is in respect of UK lives, so the report gives some insight into UK experience.

The results show that over a quarter of patients who didn’t enter ICU died, possibly reflecting assessments made as to which patients were likely to benefit from more intensive treatment. Another result of interest relates to comorbidities, with hypertension seen in 46% of those admitted.

Overall, 28% of those admitted have died, 58% have been released, and the outcomes for the remainder are as yet unknown.

Diagnosis of physical and mental health conditions in primary care during the COVID-19 pandemic

We know that the effect of the pandemic from a health perspective extends beyond those who have been infected by SARS-CoV-2. The Lancet Public Health published analysis of the indirect effect of the pandemic on general practice healthcare usage, and the effect on diagnoses of common physical and mental health conditions.

Using data from a deprived urban population, the researchers extracted weekly numbers of clinical codes entered into patient records from January to May, classified into the following high-level categories: symptoms and observations; diagnoses; prescriptions; operations and procedures; laboratory tests; and other diagnostic procedures.

In the past 10 years, the recording of all types of clinical code has increased. However, a large reduction in recording of clinical codes was observed after the onset of the COVID-19 emergency.

In this deprived urban population, diagnoses of common conditions decreased substantially between March and May 2020, suggesting a large number of patients have undiagnosed conditions.

Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge)

Improved access to diagnostics is key to controlling ongoing transmission. This article  describes the diagnostic accuracy of a point-of-care (POC), rapid, RT-PCR test known as ‘CovidNudge’. The test has been authorised by the Medicines and Healthcare Products Regulatory Agency and the validation study was undertaken in conjunction with the National Institute of Health Research (NIHR) and Public Health England.

The test kit comprises a ‘DnaCartridge’ and a processing unit. The cartridge is a disposable, sealed and integrated lab-on-chip device that enables sample-to-result PCR.

Following swab sampling, the processing unit is able to provide the pneumatic, thermal, imaging, and mechanics required to run a real-time RT-PCR reaction outside a laboratory setting.

Testing of the kit was carried out during April/May at three London hospitals, with 449 same‑day samples collected. Two swabs were taken per person, with the samples then being tested in parallel using the point of care test and the standard PCR test.

The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% with an overall specificity of 100%.

This POC test kit, whilst clearly more convenient and rapid in its result delivery, is not likely to be used for mass testing at events attended by thousands of people. Lead author of the study, Graham Cooke, stresses that the machine can only process one test at a time, with a maximum of 15 tests per machine each day. The UK government has placed an order for 5.8m of the testing kits, which it intends to roll out across the nation.

COVID-19 can affect the heart

In this article, Eric Topol explores the pathophysiology of how SARS-CoV-2 can damage the heart. Key themes include the ability of the virus to target the angiotensin-converting enzyme 2 (ACE2) receptors throughout the body with a higher affinity to that witnessed with SARS. The heart in particular is known to have high expression of ACE2.

SARS-CoV-2 has been found to directly infect heart muscle cells resulting in heart cell death and myocarditis (inflammation of the heart muscle). Worryingly, the severity of myocarditis seen in COVID-19 patients is such that the cells involved with electrical conduct in the heart are damaged which could result in arrhythmias and cardiac arrest. Topol observes that ‘These complications, which at times are the only features of coronavirus disease 2019 (COVID-19) clinical presentation, have occurred even in cases with mild symptoms and in people who did not experience any symptoms.’

Data

Understanding of and Attitudes to Symptoms and Controls

A preprint  of a survey carried out for the DHSC over the last six months has been published.   With regular surveying since mid-April, it extensively covers people’s understanding of symptoms and expected actions in different circumstances. As an example it might be surprising to learn that around half of those surveyed did not identify cough, high temperature/fever and loss of sense of smell or taste as symptoms, with this proportion not changing over time.

However, the result most likely to be highlighted in the media is the attitude to self-isolation and quarantine, where around 80% stated that they would be unlikely to obey the rules. Wide publicity of this statistic may lead to more people obeying the rules, but there’s a risk it may have the opposite effect, with people not willing to make the sacrifice if they perceive that the majority do not.

It is recognised that an effective test, track and isolate programme is essential to suppressing the virus without resorting to a further hard lockdown. For such a programme to be effective, both the government (in operating the system) and society (in responding to it appropriately) need to play their parts. Ongoing deficiencies in its operation have been well documented of late, which will in itself not have encouraged people to engage with the process. It must be imperative now to understand the drivers behind the lack of understanding and subsequent engagement with the system, as well as addressing the operational difficulties, in order to improve the overall success of the programme.

ONS

The ONS has published  an analysis of COVID-19 mortality of the working age population up to 30^th June by occupation type, subdividing by deaths where infections are believed to have occurred prior to and after the commencement of lockdown. A possibly surprising conclusion is that 72% of the 5,330 deaths contracted the virus before lockdown.

It estimates that in total the age standardised COVID-19 mortality rate fell from 117 per 100,000 for men for infections acquired pre-lockdown to 32, a reduction of over 70%, with a similar result seen for women.

Previous analysis by the ONS has shown that certain occupations had been associated with much higher mortality, an example being those in health and care settings. The latest analysis seeks to ascertain how the lockdown changed the risk level by occupation. For men, elementary occupations exhibited highest mortality for infections acquired pre-lockdown, but post-lockdown caring, leisure and other service occupations were highest, although all occupations showed significant reductions.

In contrast, for women, the caring, leisure and other service occupations were highest both pre- and post-lockdown (and the reduction was lower than average), possibly reflecting the higher proportion of women in caring roles with closer contact with COVID patients and other vulnerable groups.

As usual, Friday has also seen the publication of the latest ONS Infectivity Surveillance Survey. The results show a further sharp increase upwards as might be expected:

Other

Test case for a herd immunity approach – Manaus, Brazil

What happens if we leave things unchecked and try the herd immunity approach? Manaus, a city in Brazil with a population of 1.8m, provides a form of test case . Overall mortality from COVID-19 was of the order of 0.1-0.2%, noting that the population was young compared with typical W European profiles (6% of Manaus above age 60). The proportion infected was estimated as lying in the range 44-66% (from testing blood samples). The IFR was estimated at 0.3% (but remember the young profile).

The virus is thought to have spread very quickly – despite social distancing starting early – because of dense housing, poor water supplies, and crowding on local transport.

Lessons learnt from easing COVID-19 restrictions

The development of a vaccine or effective treatment has been widely pronounced as the only effective exit strategy from the pandemic. However, despite the intensity of the current pharma pipeline, there is absolutely no guarantee that a vaccine will be approved. In this paper published in The Lancet, the researchers examined the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (Hong Kong , Japan, New Zealand, Singapore, and South Korea) and four in Europe (Germany, Norway, Spain, and the UK).

Building on previously developed public-health principles, the research team created a comparative  framework for COVID-19 lockdown exit strategies. Using this framework, the measures taken in each of the populations studied were examined as they have eased restrictions on movement and personal interaction.

Key themes:

• The ability to implement effective find, test, trace, isolate, and support systems is highly variable across populations
• Community engagement is similarly varied; public trust in political leaders, clear, consistent communication and public confidence all contribute to adherence to introduced measures
• A failure to invest in adequate capacity before a pandemic constrains the choices that can be made

“There is increasing realisation that removing COVID-19 restrictions is not about returning to the pre-pandemic normal but about gradually and cautiously transitioning to a new normal, while being ready to reimpose measures if, and when, necessary.”

Offline: COVID-19 is not a pandemic

In this commentary piece  Richard Horton, editor-in-chief of The Lancet, describes the concept of a ‘syndemic’ (a combination of diseases with an adverse interaction), and how this relates to the current situation. He contends that a syndemic approach would reveal biological and social interactions that are important for prognosis, treatment, and health policy. This includes consideration of the fact that SARS-CoV-2 interacts with a number of non-communicable diseases and, importantly, has a social component.

“Approaching COVID-19 as a syndemic will invite a larger vision, one encompassing education, employment, housing, food, and environment. Viewing COVID-19 only as a pandemic excludes such a broader but necessary prospectus.”

And finally …

Inventive use of ‘face covering’

Whilst we should support all attempts at face covering in public, the response to one bus passenger’s attempt by a Transport for Greater Manchester spokesperson should hopefully bring a smile to your (masked or unmasked) face at the end of a difficult week!

A snake is not a facemask (shock)

25 September 2020