^{The Friday Report – Issue 21}

By Nicola Oliver, Matthew Fletcher 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 Friday update with a curated list of the key papers and articles that we’ve looked at recently.

Modelling

Reproduction number (R) and growth rate (r) of the COVID-19 epidemic in the UK: methods of estimation, data sources, causes of heterogeneity, and use as a guide in policy formation (link)

This paper from the Royal Society is a deep dive into approaches used to estimate the key epidemiological parameters R (the reproduction number) and r (the epidemic growth rate). It investigates the main UK models used to inform the UK Government, including data sources used and assumptions made – for example in relation to the time between onset of symptoms and hospital admission and death. The report also looks at parameters that could be employed to assess the impact of implementing and relaxing social distancing and other non-clinical measures used to combat the pandemic.

It concludes that, whilst wide bounds of uncertainty surround estimates of both R and r, they are still valuable to help formulate policy as guidance on a central estimate of these key figures is preferable to guessing them. The authors consider that the key improvements that can be made when estimating epidemiological parameters are clarity on the assumptions made and improving data quality.

Clinical and Medical News

T-Cell[1] Response

Evidence supporting a role for T cells in COVID-19 protection and pathogenesis is currently incomplete and sometimes conflicting. This study examined overall and immunodominant SARS-CoV-2-specific memory T cell responses in patients who had recovered from COVID-19. A total of 42 individuals were recruited following recovery from COVID-19, including 28 mild cases and 14 severe cases.

SARS-CoV-2-specific CD4+ and CD8+ T cell responses were seen in the majority of convalescent patients, with significantly larger overall T cell responses in those who had severe compared with mild disease. In addition this study reports that the proportion of the T cell response that is attributable to CD8+ (rather than CD4+) T cells is increased in mild infections; this may indicate a protective role for SARS-CoV-2-specific CD8+ T cells.

Another useful output of this study is the identification of several parts of the virus that are targeted in a cross-reactive way (i.e. immune response from a different prior corona virus) in up to half of the patients tested; this could prove useful for future immunology studies and for consideration in vaccine design.

What is the evidence for physical distancing in COVID-19?

Trisha Greenhalgh and colleagues provide a review of the evidence for physical distancing in COVID-19. The so-called ‘2 metre’ rule to prevent transmission by droplets originated from research dating back as far as 1897; this has remained the accepted distancing rule despite updated evidence suggesting that droplets can spread beyond 2 metres.

Key considerations are droplet size, force of emission, ventilation, exposure time, and crowding levels.

The figure below displays the risk of SARS-CoV-2 transmission from asymptomatic people in different settings and for different occupation times, venting, and crowding levels.

The researchers suggest that rules on distancing should reflect the multiple factors that affect risk, including ventilation, occupancy, and exposure time.

Clinical risk scores & vital signs

Clinical risk scores are used in a variety of clinical settings in order to aid decision making by medical personnel. For example, APACHE II was designed to provide a morbidity score for patients in ICU. It is useful to decide what kind of treatment or medicine is given.

Two risk scores have been developed to help with management of patients with COVID-19. The first, the 4C mortality score, was developed in order to predict mortality given that the symptoms and clinical course of COVID-19 are significantly different to other severe respiratory infections.

The researchers focused on eight metrics that play a key role in determining mortality risk – age, sex, number of underlying conditions, respiratory rate, blood oxygen concentration, level of consciousness, urea, and C-reactive protein – giving a final score out of 21. Patients with a score of at least 15 had a 62% mortality compared with 1% mortality for those with a score of 3 or less.

In addition, researchers based in Italy have identified the most appropriate risk score that can be used to predict intensive care unit admission and death for COVID-19 patients in the emergency department. Their comparative  analysis showed that in COVID-19 patients NEWS[2] and REMS[3] used on arrival at the emergency department were the most accurate scores for predicting the risk of ICU admission and death, respectively, both at 48 h and at 7 days.

Adding insights to the clinical course of COVID-19 is this analysis, which identified those vital signs which are associated with deterioration in COVID-19 patients. Patients with COVID-19 were found to deteriorate more rapidly than those with other viral pneumonias, with progressively lower oxygen saturations, greater oxygen requirements and only minor abnormalities in other vital signs.

Pause in the Oxford vaccine trial

It has been widely reported by the media that the AstraZeneca Oxford coronavirus vaccine, AZD1222, has been temporarily paused due to an unexplained illness in one of the participants. This press release from AstraZeneca states that this is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated. This is not unusual during any clinical trial.

It has also been reported, though not confirmed, that the individual concerned has developed transverse myelitis, a condition in which the messages that the spinal cord nerves send throughout the body are interrupted due to inflammation of both sides of one section of the spinal cord.

Data

ONS Infection Survey

After several weeks when the weekly survey link has reported low and stable levels of infectivity, with relatively few positive tests meaning it was difficult to draw any meaningful statistical conclusion from the results, today’s report strikes a noticeably different tone.

It reports a marked increase in the rate of positivity to 1 in 1,400 members of the community (previously it was around previously it was 1 in 2,000, with the growth in new infections now clear. ONS estimates around 3,200 new infections per day in England. Looking at variations by age and region it is perhaps no surprise to see that infections are growing rapidly in the 17 to 34 age bands, and that the North West is highest in terms of growth.

“R” updates

Also published as usual on a Friday is SAGE’s estimate of R, which is now put at 1.0 to 1.2 across the UK. Simultaneously, the government also published the latest REACT study by Imperial College link which assesses that infectivity has been doubling every 7 to 8 days since Aug 22^nd, and puts R at 1.7 (range 1.4 to 2.0). The sample size over this latest period was 150,000.

The difference can be explained by the caveat in the SAGE release that it represents transmission over the last few weeks, whereas the Imperial College survey appears more up to date, and so is picking up the sharp increase we have seen in other metrics recently. However, it is to be hoped that the confusion caused by two markedly differing results being published by the government on the same day does not undermine public confidence in the quality of statistics that are reported.

World Health Organization: Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update

Since August, the World Health Organization (WHO) have published weekly epidemiological and operational updates setting out the state of the pandemic across the world. The repository is here; the latest reports are here (epidemiological) and here (operational).

The epidemiological report sets out that globally, over 1.8 million new cases and 37,000 new deaths were reported for the week ending 6 September – an increase in cases and a decrease in deaths compared to the previous week. The Americas accounted for almost half of all new cases reported in the week, with the USA and Brazil representing almost three quarters of all cases in the region. New cases in Europe have increased substantially since a low point at the end of May, but deaths remain at a low level. India have reported around 85,000 cases a day for the past week and both cases and deaths in the South-East Asia region continue to increase rapidly.

The operational report looks at field reports of efforts to counter in various different countries, summarises the numbers of WHO-procured items (testing and PPE) in different parts of the world, and reports on the state of preparedness across the globe.

And finally …

Wine, lizards and the hazards of the mute button

Parents and carers who have been home schooling during lockdown could no doubt share many stories, both positive and negative. Some of these reflections are compiled here; take a moment to appreciate the challenges of home schooling, and the positive impact on the wine industry!

What wine pairs well with Common Core math?

— Jessie (@mommajessiec) August 24, 2020

Santé!

[1] T cells are one of the major components of the adaptive immune system. Their roles include directly killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response.

[2] National Early Warning Score (NEWS) is a tool developed by the Royal College of Physicians which improves the detection and response to clinical deterioration in adult patients and is a key element of patient safety

[3] Rapid Emergency Medicine Score (REMS) is an attenuated version of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and has utility in predicting mortality in non-surgical patients