26th May 2020 by Anne Sakoane
Vaccine manufacturers and academics are frantically working on developing a vaccine against COVID-19 but will it be too late for this current pandemic? Even if a vaccine becomes available, how can we be sure it will work?
When will a corona vaccine be ready?
Typically, a vaccine takes 10-15 years to develop, however, pandemic flu vaccine development is accelerated and can take approximately 5-6 months. The sped-up process starts with identifying the new strain of influenza virus with pandemic potential, refining bulk manufacture procedures, conducting clinical trials and finally, approval by regulatory authorities. The accelerated emergency procedure allows for fast-track approval of a new vaccine once an influenza pandemic is declared.
One US based firm started testing their candidate COVID-19 vaccine in human volunteers in a Phase 1 study7 in March and this week, researchers from the Oxford Vaccine Group have begun recruiting for Phase II/III human trials8. Other companies in pursuit of a COVID-19 vaccine include Pfizer9, Johnson & Johnson10, Sanofi Pasteur11 and GSK12.
How will we know the vaccine will work?
Did you know that in Europe, when your regular annual flu vaccine undergoes human clinical testing, it is tested for safety but not actually tested for its ‘effectiveness’ to prevent us getting the flu?
Instead, what scientists look for when testing a new flu vaccine in human clinical trials is establishing whether people get an immune response, meaning do they produce antibodies, against the flu strains in the test vaccine. This gives us an indication on whether the vaccine may be protective. In addition, there is no guarantee that the flu strains chosen to be in the vaccine will be the same circulating strains causing flu in your country during the forthcoming winter season – it’s a predictive guessing game that scientists have to manage16.
Why can’t all flu clinical trials look at true vaccine effectiveness?
Investigating whether the test flu vaccine works is challenging and often requires conducting large and expensive clinical trials. We usually observe how well a vaccine has worked after each flu season once it has been given to the population. Vaccine effectiveness varies from one season to the next and in the UK, overall effectiveness has been estimated at between 30-60% for adults aged 18 to 65 years (flu infection in primary care)19.
Can we be sure the corona vaccine will be safe?
With researchers working at breakneck speeds with pressure to develop a pandemic vaccine as fast as possible, how can we be sure the vaccine has undergone the accustomed thorough safety test requirements?
Back in 2009, during the H1N1 (swine flu) influenza pandemic, an influenza vaccine was used in several European countries which was later found to have an increased risk of narcolepsy21 (a condition that causes a person to suddenly fall asleep at inappropriate times).
For a final pandemic vaccine, large-scale safety data will be generated by using the vaccine during a pandemic and the WHO advises24 all countries administering pandemic vaccines to conduct intensive monitoring for safety and to report adverse events. In Europe, in preparation for a pandemic vaccine, some manufacturers would have conducted advance studies using a so-called “mock-up” vaccine which can greatly speed up regulatory approval.
Will there be enough vaccine to go around? Who should get the vaccine first?
Even if an experimental vaccine appears to work in clinical trials, mass producing them quickly is certainly a massive challenge. Around 90% of flu vaccines are made in chicken eggs26. Production takes six months — an eternity during a pandemic situation. Faster, alternative manufacturing techniques are emerging, such as using cell-based methods.
If there aren’t enough vaccines to go around, who gets priority? Wealthier countries? Richer individuals who can afford to pay out of their own pockets? The elderly vulnerable patients or those with underlying medical conditions? Or do we protect front line healthcare workers first?
What are my treatment options if I get the corona virus? It has been reported that intravenous vitamin C, tocilizumab/Zinc supplements/garlic/anything else has cured patients with coronavirus.
The reality is, there is no empirical evidence that any medication, chemical or substance is effective as treatment against COVID-19. Some compounds could help with symptomatic relief but are not effective medical treatments for the disease yet.
There is a difference between proposed treatments for symptoms (e.g. vitamin C) and a proposed curative treatment for the disease27.
The WHO are focusing on some promising drugs which are currently licensed for treating other conditions. These include an experimental antiviral compound called remdesivir; the malaria medications chloroquine and hydroxychloroquine; and a combination of two HIV drugs, lopinavir and ritonavir.
[-link to previous article discussing digital advancements proposing treatment]
What does it take to develop an effective treatment for a disease and have it approved for market?
The medication’s efficacy would need to be tested, it’s safety profile would have to be proven and longer-term studies on its use in wider population groups need to be studied which all take time, from 7 years and sometimes up to 12 years28.
When would a treatment for COVID-19 be ready?
One of the benefits of researching existing approved drugs is that we already know they are safe, so in theory it would take less time to get the drug approved to treat corona. Time will tell if any treatment will be available fast enough to impact the current pandemic.
What do we know about the current potential treatment, remdesivir, reported to be in use in several active clinical trials around the world?
medDigital first wrote about the Chinese and American investigations into remdesivir as a potential treatment for COVID-19 back in February 2020. Since then, it has risen in prominence as more investigative trials have opened in different countries around the world (including the WHO’s adaptive, randomised, open-label multi-centre safety and efficacy trial in hospitalised adults)30.
The Food and Drug Administration (FDA) in the USA has rapidly authorised remdesivir for the treatment of coronavirus patients but this is not a formal approval – so far, the investigative medication has not been officially approved for any purpose anywhere in the world.
Interim clinical data in the international trial has indicated remdesivir shortened recovery time from 15 to 11 days in hospitalised patients31, which resulted in a stop to the study when there was clear evidence the drug was effective.
The Principal Investigator of the study, Dr Andre Khalil of the University of Nebraska, noted that sicker patients (across the racial, gender and age spectrums) fared as well on remdesivir and their average time to recover is slightly faster, regardless of whether they began treatment before or after 10 days of symptoms32.
These results are a sign of hope for an effective treatment’s availability in the battle against COVID-19, though there is a consensus that wider scale studies and more data are needed, and as of May 2020, it looks like this will be incoming by the end of the year.
What do we know about hydroxychloroquine as a potential treatment for COVID-19?
Of all potential treatments under recent investigation, the anti-malarial drug hydroxychloroquine has been mentioned in various new media the most – likely due to the President of the United States, Donald Trump’s admission33 that he has been taking it in an attempt to prevent hydroxychloroquine.
The latest (as of 22nd May 2020) study in the Lancet reports34 that hydroxychloroquine might increase the number of deaths among those in hospital with COVID-19 (with death rates of 9% in a control group compared to 18% in patients treated with hydroxychloroquine, and even higher in those treated with a comination of hydroxychloroquine and antibiotics) and there were no benefits to treating coronavirus patients with the drug.
Shortly after this research was published, the WHO announced it had halted its testing of the drug over safety fears35. Hydoxychloroquine has been shown to be safe for malaria and conditions such as lupus or arthritis but there is no evidence from any clinical trial that it should be recommended for use in treating COVID-1936.