COVID-19 Treatment Update
During the course of the pandemic we have seen a huge wave of research and discovery into possible drug treatments for COVID-19 that has taken us all on quite a whirlwind ride.
Understandably, much of it has left us more than a little confused. Should we get our hands on a stash of hydroxychloroquine? Would spending a few hours in a hyperbaric oxygen chamber help?
Needless to say, any drug that can be rolled out for the treatment of COVID-19 infection has to be proven to be both effective and safe. The studies needed to demonstrate this have to be incredibly robust themselves – just Google “Lancetgate” for a good illustration of what can go wrong, even to the most prestigious publishers of medical research.
A good study has to have recruited adequate numbers of patients (a trial cohort of 10 is useless, even of 100 isn’t great, with more than 1,000 ideal). It has to have two “arms” to the study (with one being compared against the other). It should be randomised and “double-blind”, so nobody can influence who goes into which arm in the study and nobody knows which arm the participants are in until the data is gathered.
It also has to be consistent in the demographics of patients in either arm of the trial. That means patients with comparable severity of symptoms and other treatments received, along with the same levels of testing and reporting of symptoms and side effects, to name a few considerations. It takes time, effort and lots of money to deliver a really good study.
There are currently nearing 5,000 different trials into COVID-19 going on around the world. The World Health Organisation (WHO) has launched the Solidarity trial, which is a large international study to compare different treatments versus local standard of care alone.
In the UK, the RECOVERY trial is testing therapeutic options for people hospitalised with suspected or confirmed COVID-19. No treatments have been approved for safety and efficacy except Remdesivir, however, several drugs are being used “off license” (other than the purpose they were licensed for originally), on a compassionate-use basis or as part of a trial.
You’re probably familiar with most of the current COVID-19 treatments, as they’ve been widely covered in the news, although we’re pleased to provide our views of the treatments, based upon the latest UK guidance and the currently available evidence:
Remdesivir is an antiviral medication that has shown ‘in vitro’ (in a test tube) activity against COVID-19 infection. The Food and Drug Administration (FDA) in the USA has issued an emergency-use authorisation for Remdesivir for the treatment of suspected or confirmed Covid 19 in adults and children who are hospitalised with severe disease (low oxygen levels, needing oxygen therapy or breathing support).
Preliminary results from a large trail run by the National Institute of Allergy and Infectious Disease found that patients taking a 10 day course of Remdesivir had a faster time to recovery, compared with a placebo. The patients also had a lower mortality rate. There have also been other trials showing favourable results, in terms of recovery, when comparing Remdesivir to standard treatment or placebo.
The National Institute for Health and Care Excellence (NICE) provides guidance for evidenced-based practice in the UK reviewed all the available evidence and suggests there is some benefit with Remdesivir (when compared with placebo) for reducing supportive measures, including mechanical ventilation and reducing time to recovery in patients with mild, moderate or severe COVID-19. This was amongst patient who are on oxygen therapy, but they did not find a statistically significant difference with ‘serious adverse events’ (a common trial term for ‘potentially causing death’ event) or mortality (death).
Although it’s had lots of media coverage, Remdesivir is not a risk-free drug. It can itself cause adverse effects, such as deranged liver function, as well as infusion-related reactions e.g. nausea, vomiting, sweating, shivering and low blood pressure. If Remdesivir is used at the same time as hydroxychloroquine (see below) the antiviral activity of the drug can be reduced.
There is currently an interim clinical commissioning policy in place to define the best path towards routine access to Remdesivir for the treatment of COVID-19 in the UK.
Chloroquine and hydroxychloroquine are oral drugs that have been used for the prophylaxis (prevention) and treatment of malaria for many years. The drugs have a role in the treatment of some autoimmune conditions, such as rheumatoid arthritis and Lupus.
Initial data from some studies seemed promising, however, the evidence has been conflicted and often weak. Hydroxychloroquine is considered safe in pregnancy, is readily available in many countries and is reasonably tolerated by most people. It can interact with other medications, particularly the antibiotic azithromycin. It can also cause abnormal heart rhythms and therefore is usually only used with great caution in patients with pre-existing cardiovascular disease. Sadly, many patients do not know they have cardiovascular disease, with the first symptom in 1 in 3 patients being sudden death. That makes it really trick for doctors to use without understanding the individual patient risk profile.
Preliminary results from the RECOVERY trial found that hydroxychloroquine does not reduce the risk of dying or improve other outcomes in hospitalised patients. Investigators have stopped enrolling participants into the hydroxychloroquine arm of the trial. As a consequence of this, the WHO also stopped the hydroxychloroquine arm of the Solidarity trial on 17 June.
The Medicines and Healthcare products Regulatory Agency (MHRA) has instructed researchers in the UK who are using hydroxychloroquine in clinical trials to suspend recruitment of further participants, although hydroxychloroquine will still be able to be used in trials for the prevention of COVID-19 in healthcare workers.
This is a drug currently approved for the treatment of HIV and results from a small case series suggested there was evidence of clinical benefit from using it in the treatment of COVID-19.
Preliminary results from the RECOVERY trial found that there is no beneficial effect of lopinavir/ritonavir in hospitalised patients with COVID-19. There was no significant difference in 28-day mortality, risk of progression to mechanical ventilation, or duration of hospital stay between the two treatment arms (lopinavir/ritonavir versus usual care alone). The results were also consistent in different subgroups of patients.
Lopinavir/ritonavir may also increase the risk of a slow pulse, especially in older, critically ill patients. Currently, Lopinavir/ritonavir is only generally used in the context of a clinical trial.
Plasma is a component of blood and convalescent plasma from patients who have recovered from viral infections has been used as a treatment in viral outbreaks in the past including SARS, avian flu and Ebola.
There are ongoing trials looking into the safety and efficacy of using convalescent plasma that contains antibodies to COVID-19 infection in patients with COVID-19. A Cochrane rapid review (which reviews all of the best available evidence) found that it was unclear as to whether convalescent plasma was beneficial for patients hospitalised with COVID-19, as the completed studies were of poor quality and the results could have been related to natural progression of the disease or other treatments the patients had received.
This week the FDA has issued emergency authorisation for investigational convalescent plasma for the treatment of COVID-19 in hospitalised patients in the US. The FDA have felt that, based on evidence available, convalescent plasma may be effective in treating COVID-19 and that the known and potential benefits of the product outweigh the known and potential risks. Here in the UK, it is still felt that there is limited information regarding adverse effects and safety in patients with COVID-19 and the use of convalescent plasma is still being investigated.
Stem Cell Therapy
Stem cell therapy is being looked into for the treatment of patients with COVID-19 as it is believed that stem cells can reduce the changes that occur in the lungs amongst patients, as well as inhibit the immune inflammatory response that causes patients to deteriorate and become severely unwell.
At present, guidelines advise against the use of stem cells for the treatment of COVID-19 except in the context of a clinical trial.
These are a just few of the treatment options that have been researched and shown some promise as treatments, however, this is by not an exhaustive list.
The main message for patients and employers remains that only robust trials can prove which treatments are truly safe and effective. Sadly, robust trials and studies take time. The media are likely to keep looking for headlines in the meantime. Looking out for the number of patients involved in any trial and whether it was randomised and double-blind is the first step to consider before taking any news stories too seriously.
The UK trials are still ongoing whilst we simultaneously await a vaccine for COVID-19. Alternative treatments, such as herbal remedies, have not been investigated to the standards we’d consider as being required in order to believe any results. It’s incredibly important to beware of social media posts, or news stories, about claims for cures.
If you’re concerned about any aspect of your health, always speak to a medical practitioner at the earliest opportunity. If you’d like to learn more about our healthcare services for employers, just click here.
Dr. Sidra Malik BMBS MRCGP DRCOG DFSRH
27th August 2020