COVID-ARG.COM

^{Monthly medical update – Issue 4}

Nicola

Dan

^{30 October 2020}

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. We will aim for these summaries to be accurate as at the date of publication, but they will of course date rapidly, so we plan to issue an updated summary each month.

Vaccines

As at 19 October 2020, the following potential vaccines were in clinical trials:

The number of vaccine trials in phase 1 have increased by 7, and those in phase 1-2, phase 2 and phase 3 are broadly the same since our last update on 2 October 2020.

In addition, there are 217 preclinical trials in progress for vaccines to tackle SARS-CoV-2, a big jump from 151 last month. Here is a quick reminder of the clinical trial process showing the purpose of each stage and the attrition rate from stage to stage:

We do not yet have results from any of the crucial phase 3 trials.

Last month, the vaccine development team at Oxford expressed an expressed interest in conducting ‘challenge studies’ on humans, meaning they would deliberately infect low-risk volunteers with the virus, either alongside phase 3 trials or after they are complete. On 20 October, it was announced that a partnership between the NHS, academia and the private sector will be formed in order to explore and establish human challenge trials. This is not the first time that such trials have been conducted;  treatments for diseases including malaria, typhoid, cholera, norovirus and flu have also been investigated in this way.

The Joint Committee on Vaccination and Immunisation (JCVI) updated the interim advice on priority groups for COVID-19 vaccination on 25 September. Vaccination priority groups are as follows:

1. older adults’ resident in a care home and care home workers
2. all those 80 years of age and over and health and social care workers
3. all those 75 years of age and over
4. all those 70 years of age and over
5. all those 65 years of age and over
6. high-risk adults under 65 years of age
7. moderate-risk adults under 65 years of age
8. all those 60 years of age and over
9. all those 55 years of age and over
10. all those 50 years of age and over
11. rest of the population (priority to be determined)

Kate Bingham, chair of the Vaccine Taskforce, cautions against being overly optimistic regarding a potential vaccine, ‘we do not know that we will ever have a vaccine at all. It is important to guard against complacency and over-optimism’. (link)

The European Medicines Agency (EMA) have started the first rolling review of a COVID-19 vaccine, which is being developed by the company AstraZeneca in collaboration with the University of Oxford. The start of the rolling review means that the committee has started evaluating the first batch of data on the vaccine, which come from laboratory studies (non-clinical data). (Normally, all data from all stages of the drug trial are submitted at the start of the evaluation; in this case, data will be submitted as it becomes available in order to speed up the approval process).

The rolling review will continue until enough evidence is available to support a formal marketing authorisation application.

Treatment

There has been considerable interest in the use of convalescent plasma to improve clinical outcomes for those with COVID-19. Early studies without a RCT framework were considered by the FDA as providing sufficient evidence to justify issuing emergency use authorisation on 23^rd August.

A more recent RCT trial in India considered the addition of convalescent plasma to best standard of care for 464 adults with moderate COVID-19 (oxygen saturation of less than 93%). The trial concluded that there was no significant impact on progression to severe disease or death over a period of 28 days post-enrolment, with 18-19% progressing in both arms of the trial.

However, further investigation may be warranted as the trial did not consider whether clinical outcomes differed by antibody concentration in the contributing donors. There are ongoing RCT trials in the UK, namely REMAP-CAP and RECOVERY, that are managed by the NHSBT Clinical Trials Unit.

Testing

The ongoing REACT-1 study is carrying out rt-PCR tests on random samples (c. 100,000) of the English population.  Initial results from round 6 of the study considered swabs obtained from 16^th to 25^th October and indicated a weighted prevalence of viral infections of 128 per 10,000 population, more than double the prevalence of round 5 in September. The highest prevalence in round 6 remains those aged 18-24 yrs (2.25%), but the highest rate of growth was in those aged 55-64 yrs. The report has been used to estimate that 960,000 would currently be positive if tested, and that there are now 96,000 new infections every day. The table below illustrates the prevalence of positive swabs from all of the different rounds so far in the REACT-1 study.

Antibodies

The REACT-2 study has now carried out three cross-sectional surveys in England between June and September 2020, involving self-administered immunoassay tests on 365,000 adults. Initial results comparing the different surveys indicate that the prevalence of IgG antibodies has declined from 6.0% to 4.8% to 4.4% between the different surveys, with those aged 75+ showing the lowest prevalence and the greatest decline over the period.

This is of particular concern when considering whether older persons are able to generate and maintain a sufficient and competent immune reaction to SARS-CoV-2. That said, it has not yet been confirmed that declining levels of antibodies increase the potential for re-infection with SARS-CoV-2, because of uncertainty over the relative contribution made by T-cells and long-lived memory B Cells to the immune response. However, there are a number of further findings that are highly relevant:

• Seasonal coronaviruses show declining levels of antibodies after infection which are consistent with a 1-2 year periodicity of reinfection whereas antibodies levels for rhinoviruses remain constant for a year after prior infection.
• Declines in antibodies over the three surveys were largest in those that did not report a history of COVID-19 (-64% vs -22%)
• There appears to be no change in the prevalence of antibodies between surveys in healthcare workers, who might reasonably be expected to have had more frequent and more significant exposure.

At the same time, a further study from Professor Florian Krammer at Mount Sinai (Icahn School of Medicine) on 30,000 individuals who had previously tested positive for COVID-19 demonstrated that 90% of these seroconverters were still able to generate detectable neutralising antibody responses more than 5 months after prior infection.

Long COVID

We recently covered the emerging condition described as long COVID. Two recent publications have sought to explore this condition. The first , a dynamic review of the evidence around ongoing COVID-19 symptoms conducted by the NIHR identified the lack of consensus on diagnostic criteria, the increased risk in vulnerable groups and that there is likely to be significant psychological and social impacts that will have long-term consequences for individuals and for society if not well managed.

The second, using data from the Covid Symptoms Study App developed by Zoe Global Limited, sought to identify attributes and predictors of long COVID. Those experiencing long-COVID were consistently older, female and were more likely to require hospital assessment than in the group reporting symptoms for a short period of time. In addition, early disease features were predictive of duration.

30 October 2020