^{The Friday Report – Issue 16}

By Matt Fletcher and Dan Ryan

Dan Ryan and Matt Fletcher

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

Every week, more is written on COVID-19 than any individual could possibly read. Collectively, the COVID‑19 Actuaries Response Group read more about the outbreak than most, so we’ve decided each Friday to provide you with a curated list of the key papers and articles that we’ve looked at recently.

Modelling – reports

We have recently published briefings on seasonality and death rates in hospitals, These two relatively new papers cover similar topics.

Effects of environmental factors on severity and mortality of COVID-19 (Kifer et al)

This paper examines the progression of COVID-19 in around 7,000 hospital patients in Europe and China, as well as around 37,000 individuals reporting symptoms into the COVID Symptom Study app in the UK. It finds that the mortality risk reduced by date of admission and by increase in ambient temperature – it also finds that the need to move to intensive care or require mechanical ventilation was often reduced, and that symptom duration and disease severity has reduced over time in those who were not hospitalised. The authors consider that the most likely explanation is the seasonality of COVID-19. The paper has not yet been peer reviewed.

Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies (RA Armstrong, AD Kane, TM Cook) 

This paper carries out a systematic review and meta-analysis to assess reported intensive care mortality for patients with confirmed cases of COVID-19. A total of 24 studies including over 10,000 patients were included, across Asia, Europe and North America. There was a wide range of reported mortality across the studies; the meta-analysis found that in-ICU mortality from COVID-19 is higher than for other viral pneumonias, but that the reported mortality rates have fallen from over 50% to close to 40% over the period of the outbreak.

Women-led governments more successful in containing COVID-19 pandemic 

This pre-print of a study of 35 countries identifies that those with women-led governments experienced fewer COVID-19 deaths per capita and were more successful in flattening the first wave. The study called out Tsai Ing-Wen in Taiwan, Katrín Jakobsdóttir in Iceland and Jacinda Ardern in New Zealand for their rapid deployment of targeted restrictions and emphasis on public health over short term economic activity. The study suggested that women are more likely to be in positions of leadership in societies that value nurturing and collaboration, and that are healthier and more resilient to external shocks.

Clinical and Medical News

Human Challenge Trials

An open letter from 100 leading scientists has called for the introduction of “human challenge trials” to assist with vaccine development. The ongoing COVID-19 Infection Survey has estimated that only 1 in 3,900 people have an active infection – as such it is almost impossible to determine whether a vaccine is effective or not. The Phase III trial led by Professor Sarah Gilbert at Oxford University’s Jenner Institute has already set up parallel trials in Brazil and South Africa where the virus is circulating more widely, and AstraZeneca is about to start a further 30,000 person trial in the USA.

The “human challenge trials” would deliberately infect individuals with COVID-19. The concept is not new, but the lack of an effective treatment raises ethical issues. The open letter highlights the very low mortality rates of COVID-19 amongst young adults, similar to living kidney donors, and the many lives that could be saved by rapid assessment of different vaccine programmes.

The Oxford group has begun preparations for such human challenge trials that would be expected to run in parallel with the existing Phase III trials. This builds on positive indications from their Phase 1 trials on 1,000 volunteers where the vaccine is believed to have stimulated an effective immune response with both antibodies and T-cells. Official results will be published next Monday in the Lancet.

Management of Acute Coronary Syndrome

An in-depth study  of the Secondary Uses Service Admitted Patient Care Database identified that hospital admissions related to heart attack and unstable angina had reduced in England by 40% in the last week of March and were still 16% lower in the last week of May than the equivalent figures for 2019. In total, this would represent 8,000 fewer admissions for acute coronary syndrome.

The reduction is heavily associated with fear of infection as the decline started a month before lockdown, and began to improve with the release of a publicity campaign in April by the British Heart Foundation and British Cardiovascular Society.

COVAX – Facility

According to the Coalition of Epidemic Preparedness Innovation (CEPI), 75 countries have expressed interest in joining the COVAX-Facility. Under the Facility, countries make an upfront commitment to purchase a pre-defined number of doses and in return receive access to a variety of successful vaccine candidates at affordable negotiated prices.

This complements the COVAX Advance Market Commitment that provides demand certainty to manufacturers in exchange for timely dose supply. Partnerships with 90 lower-income countries through voluntary donations mean that 60% of the world’s population would be covered.

Deep immune profiling

A key challenge to understanding COVID-19 is that the immune response to infection appears to be very heterogeneous. Profiling of T-cells and B-cells in the immune system for 125 COVID-19 patients admitted to the Hospital of the University of Pennsylvania identified three immunotypes or groups with poor client prognosis where T-cells were either poorly activated or not at all, or appeared to be exhausted.

Data

ONS: Deaths Involving COVID-19, England and Wales: deaths occurring in June 2020 

ONS have published a lengthy summary of deaths involving COVID-19 in each month in England and Wales, splitting by age, sex and date of death. Around 23% of deaths between 1 March and 30 June 2020 related to COVID-19 – there were 218,837 deaths in total and 50,335 involving COVID‑19. The majority of these (46,736) had COVID-19 as the underlying cause of death (including 3,763 classified as “suspected” COVID-19 – others had COVID-19 mentioned on the death certificate but not as an underlying cause.

In June 2020, just over 7% of deaths occurring were as a result of COVID-19 – a reduction compared to April and May. This still made COVID-19 the third most frequent underlying cause of death in both England and Wales, behind ischaemic heart disease and dementia / Alzheimer disease. Males had higher rates of COVID-19 deaths than females at all ages, a similar pattern to previous months, and those aged 90 and over made up the largest proportion of COVID-19 deaths.

ONS have also recorded the main pre-existing conditions for those deaths involving COVID-19 – in March to June 2020, the most common pre-existing condition was dementia / Alzheimer’s disease, occurring in 25.6% of deaths involving COVID-19. Ischaemic heart disease (9.9% of deaths) is the second most common condition. The proportion of deaths with no pre-existing condition was below 10% in those aged 70 and over, and somewhat higher (around 10% for females and 15% for males) for those aged 0 to 69. Whilst the average number of pre-existing conditions for deaths involving COVID-19 varies by age and sex, it was over 2 for men and women at ages below and above 70.

Public Health England – reporting of COVID-19 deaths

Following a call by Matt Hancock for a national inquiry, Public Health England have confirmed  that their statistics for COVID-19 deaths in England include all those who have died who had a positive COVID-19 test at any point, regardless of the ultimate cause of death. As we move through the outbreak, this approach is likely to over-count deaths (for example, someone who tested positive for COVID-19 in March but died of a heart attack in July is currently counted as a COVID-19 death even though it may be arguable whether COVID-19 is a direct cause).

PHE have noted that, of 40,528 COVID-19 deaths reported by 15 July, 90% occurred within 28 days of a positive test, and of those dying after 28 days, 47% had COVID-19 recorded as the main cause. If only those dying within 28 days of a positive test were counted, a total of 35,664 deaths would be included.

These adjustments will not change the excess mortality figures that are calculated based on the data published by ONS – they may, however, mean that recent death figures are higher than equivalents in other countries who may count COVID-19 deaths in a different way.

And finally…..

During lockdown, cinemas were replaced by Netflix, gyms replaced by rearranged living rooms, and so on … But how has the world of ‘close-up magic’ fared, where the impact lies in being at arm’s length from the performer, looking for the misdirection and sleights?

A new genre of remote card magic has appeared, with magicians making the cards dance in the spectators’ hands, but with no chance for sleight of hand. Not completely new, as Spain’s most famous magician had been performing such magic via a Spanish radio show many years ago (effects described in his book ‘Verbal Magic’, or ‘Por Arte de Verbi-magia’). Links to videos of the tricks are here and here.

17 July 2020