Friday Report: Issue 36
By 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 Friday update with a curated list of the key papers and articles that we’ve looked at recently.
Clinical and Medical News
COVID-19: patient characteristics in the first phase of post-intensive care rehabilitation
It is well established that those discharged form intensive care are at risk of suffering from ‘post-intensive care syndrome’. It is thought that this affects around half of those who have been through the traumatic experience of intensive care admission. In this analysis of a Dutch cohort, researchers describe the clinical characteristics of post-ICU COVID-19 patients, admitted for inpatient rehabilitation. Whilst many of the post-COIVD-19 patients display similar physical and anxiety symptoms to other post-ICU patients, unique characteristics included drop in oxygen levels on exertion, severely reduced overall muscle force and swallowing problems.
Maximizing Fit for Cloth and Medical Procedure Masks to Improve Performance
The CDC, in their regular Morbidity and Mortality Weekly Report (MMWR) reporting, present the results of experiments in which they assessed two ways of improving the fit of medical procedure masks: fitting a cloth mask over a medical procedure mask; and knotting the ear loops of a medical procedure mask and then tucking in and flattening the extra material close to the face. link
The authors report that when measuring efficacy with a ‘simulated’ cough:
An unknotted medical mask blocks 42% of particles
A cloth mask blocks 44.3% of particles
Combination of cloth over medical mask blocks 92.5% of particles
Both the masked and the unmasked benefit from ensuring greater fit as displayed in the next figure, which shows mean cumulative exposure for various combinations of no mask, double masks, and unknotted and knotted/tucked medical procedure masks.
Repurposed Antiviral Drugs for Covid-19
Antiviral drugs work in a number of different ways, each designed to slow down attachment and replication of the virus within the host. The WHO Solidarity trial recently published results of a study in which existing ant-viral drugs remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a, were tested for their impact on mortality. link Across 30 countries, 11,330 participants were included. Unfortunately, no drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospital duration.
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers
Whether the presence of SARS-CoV-2 antibodies is associated with the risk of subsequent reinfection is the subject of analysis by the Oxford University Hospitals Staff Testing Group. link Baseline antibody status of healthcare workers in the UK was ascertained through PCR testing and determined through anti-spike (primary analysis) and anti-nucleocapsid IgG assays. The study included 12,541 participants.
11,364 participants were followed up after negative antibody results and 1265 after positive results.
Of those who tested negative, 223 had a positive PCR test, 100 during asymptomatic screening and 123 while symptomatic.
The incidence of polymerase-chain-reaction (PCR) tests that were positive for SARS-CoV-2 infection during the period from April through November 2020 is shown per 10,000 days at risk among health care workers according to their antibody status at baseline. The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months.
CD24 to treat COVID-19
Promising early trial results have been reported following the trial of a drug based on CD-24. This is a protein expressed on a number of human cells which are central to the immune system and in particular, play a role in inflammation and the cytokine response. In this study carried out in Israel, the nasally administered drug known as EXO-CD24 was reported to have induced recovery in 29 out of 30 moderate-to-severe COVID-19 patients within 3 to 5 days. The 30th patient also recovered but over a longer time period. It is hoped that further clinical trials will be approved.
Surveillance of common respiratory infections during COVID-19 pandemic (pre-print)
Data is emerging on the reduction in prevalence of other viral infections as a result of the various measures taken to reduce the transmission of SARS-CoV-2. This survey of common viral respiratory infections that have a similar pattern of transmission, tropism, and clinical manifestation as COVID-19 undertaken in China reports that the rates for common respiratory infections, such as influenza and respiratory syncytial virus infections, decreased dramatically from previous annual 13.7% (95% CI, 10.82-16.58) and 4.64% (95% CI, 2.88-7.64) to 0.73% (95% CI, 0.02-1.44) and 0.0%, respectively, in this season.
The Sputnik vaccine
The recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V) has been approved for use in Russia since December 2020 amid some controversy given that this was done on the strength of phase I/II studies. The phase III study results have now been published. link
Between September and November 2020 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476). 19,866 received two doses of vaccine or placebo and were included in the primary outcome analysis.
Kaplan-Meier cumulative incidence curves for the first symptomatic, PCR-positive COVID-19 after dose 1, in participants who received at least one dose of vaccine or placebo are displayed in the figure below.
Estimated vaccine efficacy against confirmed COVID-19 occurring at any time after dose 1 was 73·1% (95% CI 63·7–80·1). Notably, in the vaccine group, most cases of COVID-19 occurred before dose 2.
The next figure displays (A) Receptor-binding domain-specific antibodies on day 42, as measured by ELISA, in participants administered with vaccine, by age group and overall, or placebo overall. (B) Neutralising antibodies on day 42, as measured by neutralisation assay with 100 TCID50, in participants administered with vaccine or placebo. Data are divided by age strata and by sex.
These interim results of the phase 3 Gam-COVID-Vac trial show that the vaccine is 91·6% (95% CI 85·6–95·2) efficacious against COVID-19 (from day 21 after first dose, the day of receiving second dose). Our results also showed that the vaccine was 100% (95% CI 94·4–100) efficacious against severe COVID-19, although this was a secondary outcome, so the results are preliminary.
Vaccine-induced immunity against emerging variants
With the emergence of new SARS-CoV-2 variants of concern, (VOC), there is of course concern that the currently approved arsenal of vaccines may not be as effective in these cases. Researchers from the Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical Group and colleagues have published a pre-print in which they find that two doses of the Pfizer vaccine have been found to have strong T-cell responses against the Kent and South African variants. link
The researchers also suggest that their data indicate that VOCs may evade naturally acquired protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine.
Impact of Priority Groups on Hospitalisations and Deaths
A paper published today in Anaesthesia by Prof Tim Cook of Bristol University and John Roberts of our group has extended our previous work to predict when the vaccination programme will start to impact on hospital pressures and deaths. With lockdown bringing underlying levels of prevalence down quite quickly currently, these modelled effects will be multiplicative to those from any change in prevalence.
The paper suggests that we should start to see the impact on deaths accelerate rapidly over the remainder of the month, although a significant impact on hospitals, and in particular ICU’s, will be less apparent until well into March and April respectively as the vaccination programme extends beyond the initial target of completing the first four priority groups by the 15th February.
By the end of March we should be seeing a 70% fall in admissions, a 50% fall in ICU admissions, but an 85% fall in deaths, reinforcing the benefits of the priority groups adopted by the government.
ONS Study on Deaths by Disability Status (link)
A feature on the BBC news last night was headlined that 60% of COVID deaths were disabled, linking to an ONS study on the subject. Slightly taken-aback by this startling statistic, on investigation the report itself notes that disability was self-reported (in the 2011 census) and defined as “day to day activities limited a little” or “day to day activities limited a lot”, including limitations due to old age.
We know that around 80% of those who have died from COVID are over aged 70, so it’s possibly not surprising that a larger proportion of these self-reported an element of limitation in the ability to perform day to day activities.
Whilst there is undoubtedly a raised level of COVID related risk for the disabled, at whatever age, and that is clearly of concern, the BBC reporting of the subject appeared to give a rather misleading impression as to the breakdown of overall deaths, and the extent of that relative risk once age and other factors are taken into consideration.
The latest infectivity survey from ONS shows great progress in all four nations, with falls averaging around 20% in the last week, with England now at 1.28%, compared with the 2% of just a few weeks ago. The survey also includes data on the relative prevalence of the new variant – of those cases where the variant could be identified, around 90% were the new “Kent” variant.
One slightly puzzling feature of the survey over the last couple of weeks has been in relation to the age breakdown. This shows that at all ages the modelled result is put at 1.2 or under, in contrast to the aggregate result of 1.28%.
“R” Rate (link)
The latest SAGE update of its estimate for R has fallen again this week, and is now at a range of 0.7 to 0.9 for both the UK and England. Notably all regions are showing a maximum range of less than 1.0, so there is certainty that the virus is currently retreating. London in particular shows a range of 0.6 to 0.8, consistent with the steep falls it has seen recently.
Our own estimate of R, based on admissions is consistent with the SAGE estimate, at around 0.75 . We expect to have to discontinue this estimate soon, as a reduction in hospitalisations from the oldest lives, will mean that admissions will no longer be representative of overall prevalence levels.
With four days left to report before the 15th February deadline, around 14m have now been vaccinated, so it looks very likely that the target of offering a vaccine to all in Groups 1 to 4 (approximately 14.6m people) will be achieved. Indeed, it is likely that more than that number will have actually received their first dose by that date.
The programme doesn’t stop there though, and although there is some talk of a slowdown in vaccine supply over the next couple of weeks, one of your correspondents (Group 6) received his invitation today, and can report an incredibly slick process in booking – from receipt of the text message invitation to confirmation of the booking in less than one minute. It certainly seems as though to date the programme is going more smoothly than many could have hoped for.
Happy Chinese New Year!
In the Gregorian calendar, the Chinese New Year begins at the new moon that falls between 21 January and 20 February. For this year it is today Friday, 12 February. (Today’s date is also a palindrome and an ambigram…)
And it marks the beginning of the Year of the Cow.
Today is also the birthday of the great British biologist, Charles Darwin, was born on this date 12 February – 212 years ago in 1819. He made a decisive move in us understanding the nature of biology, evolution and theory of selection.
With regard to the pandemic, now is the time which marks the descent of death and hospitalisation numbers as vaccination takes root.
And of course, vaccination is another great British discovery. The smallpox vaccine, introduced by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that inoculated vaccinia protected against inoculated variola virus.