Monthly medical update – Issue 6
31 January 2021
By Nicola Oliver and Dan Ryan for
COVID-19 Actuaries Response Group – Learn. Share. Educate. Influence.
Given the pace of change with ‘all things COVID’, it can be hard – even for those who follow all the updates – to know what the overall state of play is regarding medical developments in particular, as opposed to just the most recent news. In this new type of Bulletin, we provide a summary of what we believe the current medical position to be.
There are now eight COVID-19 vaccines that have achieved regulatory approval, as follows:.
|Federal Budgetary Research Institution State Research Centre, Russia||Peptide|
As at 26 January 2021, the following potential vaccines were in clinical trials:
|Stage||Phase 1||Phase 1/2||Phase 2||Phase 2/3||Phase 3|
There has been a significant reduction in the phase 1 pool over the last 6 weeks; this is not surprising given the attrition rate usually seen at this phase. There are 173 in pre-clinical evaluation, a small increase since our last report.
The UK and many other countries are now well into their vaccination programmes. The aim of the UK is to have vaccinated everyone in the top 4 priority groups by 15 February. As a reminder, these groups are:
- all residents in a care home for older adults and their carers
- all those 80 years of age and over and frontline health and social care workers
- all those 75 years of age and over
- all those 70 years of age and over and clinically extremely vulnerable Individuals
The UK vaccination programme has now delivered 8.4 million first doses of a COVID vaccine. These are either those developed by Pfizer/BioNTech or AstraZeneca/Oxford. The Moderna vaccine has been approved for use in the UK but rollout has not yet started. The chart below, courtesy of John Roberts, shows that reaching the target is looking feasible but far from certain (by comparison of the gradient of the solid green line, actual jabs, to that of the dashed green line, required jabs).
Changes to the dosing schedule by the UK has raised some concerns, these are outlined in Bulletin 98. In brief, vaccination dosing guidelines that fall outside of those stipulated by the manufacturer pose a potential threat to vaccine effectiveness, as well as a possibly increased chance that novel and significant mutational strains appear.
Worldwide vaccine doses are nearing 100 million. Doses administered by population shows that Israel is way ahead with a rate of 55 per 100 people.
The Novavax vaccine based on protein sub-units has just announced promising results in preliminary analysis of a phase 3 trial. l(ink) The study enrolled more than 15,000 participants between 18-84 years of age, including 27% over the age of 65. The first interim analysis is based on 62 cases, of which 56 cases of COVID-19 were observed in the placebo group versus 6 cases observed in the NVX-CoV2373 group, resulting in a point estimate of vaccine efficacy of 89% (95% CI: 75 – 95).
The UK has secured 60 million doses, but delivery will not take place until the second half of this year.
Characteristics of those vaccinated
The OpenSAFELY collaborative have published a pre-print analysis looking at the trends, regional variation and clinical characteristics of COVID-19 vaccine recipients. Analysis was conducted on routine clinical data from 23.4 million adults. The study identified 961,580 people out of the dataset between 8 December 2020 and 13 January 2021 who had received a COVID-19 vaccine. (Vaccination information is transmitted back to patients’ primary care records over the days following administration).
This study reports that disparities in vaccination are evident; vaccination rates were lower in those from a black background, in more deprived groups, those with severe mental illness and those with learning disabilities. For other co-morbidities, patients were equally likely, or more likely, to have received a vaccine. The study also reports substantial variation in vaccination among the over-80s between Sustainability and Transformation Partnerships ranging from 12-74%.
Throughout the pandemic the RECOVERY trial has been evaluating a range of potential treatments in the UK for COVID-19. The treatments that continue to be investigated has reduced to the following:
- Colcichine (commonly used anti-inflammatory)
- Regeneron’s antibody cocktail (a combination of monoclonal antibodies)
- Aspirin (commonly used to thin the blood).
This follows the closure of the convalescent plasma arm of the RECOVERY trial on 15 January. Preliminary analysis based on 1,873 deaths in 10,406 patients had found no significant difference in 28-day mortality between those on standard care (18%) and those also receiving convalescent plasma.
On the same day, the FDA in the USA issued revised guidance that repeated that the FDA had not yet approved convalescent plasma, but allowed the continued use off convalescent plasma therapy under Emergency Use Authorisation or in ongoing clinical trials.
The continuing REACT-1 study completed its 8th round of testing yesterday, and reported that the prevalence of SARS-CoV-2 infections was 157 per 10,000 population, the highest since the beginning of the study in May 2020. This was based on 167,642 swabs taken between 6-22 January. A regional breakdown indicated that the highest rates of infection were seen in London and the East of England (2.83% and 1.78% respectively) and the lowest prevalence in the South West at 0.87%.
The study further found that the most predictive factors for infection were as follows:
- Those of black and Asian ethnicity had prevalence of 3.07% and 2.60% respectively, compared with those of white ethnicity at 1.22%
- Larger household size
- Those living in neighbourhoods in the two most deprived quintiles had prevalence of 1.95% and 1.79% respectively, compared with those living in the least deprived quintile at 1.22%.
The table below illustrates the prevalence of positive swabs from the eight rounds of testing so far in the REACT-1 study.
The REACT-2 study reported further data from December on 19 January based on self-administered immunoassay tests as part of the COVID-19 Infection Survey. Initial results indicated that an estimated 1 in 8 people would test positive for antibodies in England, increasing from 1 in 20 back in September. The prevalence rates in December were estimated to be lower in the devolved countries, being 1 in 10 for Wales, 1 in 11 in Scotland and 1 in 13 in Northern Ireland.
Further analysis on the regional breakdown in England, and illustrated in the table below, indicated that the highest prevalence of antibodies was expected to be in Yorkshire and the Humber (16.8%) as compared to 4.9% in the South West.
The decline of antibody levels seen in prior studies would suggest that these prevalence rates understate the percentage of the population that have been infected with the SARS-CoV-2 virus and would be expected to be higher now in January given the level of reported infections since the New Year and the higher transmissibility rate of the B.1.1.7 variant.
The ONS published analysis of long COVID prevalence in December and estimated that at least 10% of those testing positive for COVID exhibit symptoms for a period of 12 weeks or longer.
Epidemiology of post-COVID syndrome following hospitalisation
Rates of readmission following hospitalisation with COVID-19 could be around 30%. Professor Kamlesh Khunti led a team of academics that analysed linked datasets in England including all individuals hospitalised with COVID-19 between 1 January 2020 and 31 August 2020 (link). This study also reports increased mortality risk following discharge from being hospitalised with COVID-19. These post-discharge events were observed to be higher in those aged ≥70 years than <70 years, and for those of White ethnic background than in the Non-White group. When contrasted against the background rates of adverse events that might be expected to occur in these groups in the general population, younger and ethnic minority individuals faced greater relative risks than those aged ≥70 years and those in the White group, respectively.
Elevated rates of multi-organ dysfunction were also observed in those discharged from hospital. This was observed across all age ranges and ethnicities.
Long-term mental health impact
Emerging evidence also points to long-term damage to mental health following COVID-19. A large US study using electronic health records from 69 million individuals of whom 62,354 had a diagnosis of COVID-19 sought to assess whether a diagnosis of COVID-19 was associated with increased rates of subsequent psychiatric diagnoses, and whether patients with a history of psychiatric illness are at a higher risk of being diagnosed with COVID-19.
A significantly higher rate of psychiatric disorders were reported in COVID-19 survivors, including dementia and insomnia as well as anxiety and depression. This study reports a doubling of risk of being newly diagnosed with a psychiatric disorder after COVID-19 diagnosis.
31 January 2021