Doctors seek new solutions for helping seriously ill Covid-19 patients

“The single most important thing we have done is to restrict population movement and introduce social distancing early. This bought Ireland’s healthcare system extra time in preparing for this pandemic, especially relative to the UK,” respiratory consultant Oisin O’Connell stresses.

However, even when serious cases occur, doctors increasingly have a variety of treatment options as their understanding of the disease, and international learning on it, broadens.

“We expect the disease to come in waves, and with each wave we want to be able to have learned from previous ones,” O’Connell says.

About 15 per cent of patients will require hospitalisation, and 5 per cent will need to be admitted to ICU. In countries where systems were overloaded, over half of the ICU patients have died but Irish figures could be better if we can remain within our surge capacity.

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“Patients are referred to the ICU because they fail to maintain adequate levels of oxygen in their blood despite having an oxygen mask,” explains Dr Michael O’Dwyer, head of critical care at St Vincent’s Hospital.

These patients then require mechanical ventilation in an ICU. “Our experience is that patients with Covid-19 coming to an ICU require a period of 7-14 days, at least, on a ventilator before their lung function improves substantially.”

While many patients improve with this standard treatment, given the vast numbers involved researchers have been searching for additional treatments to shorten the length of the disease and improve death rates.

“Whilst most of the motivation in this field is altruistic, undoubtedly financial gain and academic progression also plays a role,” O’Dwyer cautions.

Hypoxia

Doctors have learned Covid-19 can manifest itself in different ways among different groups of seriously ill patients. Many patients will show the classic signs of oxygen depletion known as “hypoxia” and respiratory distress associated with various subtypes of pneumonitis, which are a form of inflammatory condition of the lung tissue. They are increasingly recognising patients can display several patterns of pneumonitis.

Furthermore, doctors are learning therapies may have to vary according to the different "phenotypes", or patterns, the disease displays in individual patients, according to O'Connell. Many of these therapies will be undergoing international trials that Ireland hopes to join such as the World Health Organisation-endorsed "Solidarity" trial, but due to the international emergency specific therapies are also being used in a more limited fashion in medical settings across the world.

While the peer review of research is being expedited, O’Dwyer says a potential downside is the administration of treatments “that have no real beneficial effects but do have poorly understood detrimental effects”.

“It also makes robust randomised trials more difficult to perform because all patients want the widely advertised cure (despite the lack of evidence and potential for harm) and are therefore unwilling to participate when they may end up in the placebo arm of a trial.”

"There simply cannot be any trade-off in standards for drug development and testing," says Dr Liz O'Brien, chief medical officer of Befins Healthcare and a former pharmaceutical regulator. "These rules are there for a reason. You pose a real risk to society if you lower standards and put something out that millions of people could be exposed to."

Highly lucrative

Nonetheless, doctors continue to search for new options, while drug companies are researching products that could prove highly lucrative. Some of these drugs are new, and others are existing drugs for which new uses are being tested.

Remdesivir, an anti-viral tried out during the Ebola epidemic, is the drug that has attracted most attention, not hindered by the way very limited – and positive – results of a trial were leaked last week.

For specific patients, Tocilizumab, traditionally used to treat rheumatoid arthritis, can be repurposed to decrease an extreme inflammatory response. “In some patients, it may be beneficial if introduced at the right time, and in the right context,” O’Connell says.

Another approach tried in China for some patients with a poor immune function is a form of immunoglobulin therapy involving the use of pooled plasma from recovered patients to treat seriously ill patients.

"This could prove beneficial, but it needs to be done in an evidence-based setting, with proper monitoring for side-effects," he says. The recently established National Research Ethics Committee for Covid-19 is providing supports for expedited study and clinical trials in this context.

Other seriously ill Covid-19 patients have developed tiny lung clots (known as micro-thrombi) which can cause local damage either in the lungs or other areas of the body. There are several international research studies examining blood thinners and clot-busting medications for some of these patients.

Chloroquine and hydroxychloroquine, traditionally used to treat malaria and lupus respectively, as well as the antibiotic azithromycin, are being studied internationally also, but they may pose a serious risk of heart arrhythmia.

Genetic factors

Beyond individual treatments, scientists have observed that genetic factors may predispose particular patients – such as those with high blood pressure, obesity and other genetic innate immunity factors – to the disease.

O’Dwyer’s view is that there are lots of “interesting” potential treatments available but they remain experimental because of the lack of good trial data.

“Because of this we should be much more aggressive in enrolling patients into trials so that we expedite the process of generating useful information.”

He urges caution about advocating treatment outside of a trial because of the potential for harm. “Our best treatment option today is high-quality supportive ICU care in a well-resourced environment whilst participating in the ongoing clinical trials where these are available.”

Most hopes are pinned on a vaccine, of which many prototypes are currently in development. But it may take years for a vaccine to be properly tested and even then, virus mutation could pose a further challenge.

O’Brien says it may be that that “there is no solution to the virus other than supportive therapy, societal changes and ‘taking the hit’.”