JULY 09, 2021
- The global race for effective Covid-19 treatments is ongoing
- Large-scale clinical trials are still underway in search of the most promising drugs
- Infectious disease experts here said much progress has been made in the past year
- Unlike in the early days of the pandemic, data now shows which treatments are effective
SINGAPORE — As nations around the world race to get their people inoculated as an exit strategy to Covid-19, using vaccines hailed as a "scientific miracle" given their rapid development, medical experts are still working to find the best treatments for those who become ill from the coronavirus.
Several large-scale clinical trials are still underway around the globe to assess and determine the most promising drugs that can be used to treat Covid-19 even when most people are fully vaccinated.
TODAY takes a closer look at how Covid-19 treatments have progressed over the course of the pandemic.
While vaccination remains a key priority for many counties in managing and getting out of the ongoing pandemic, infectious disease experts said that effective Covid-19 treatments are still necessary because they can be life-saving for the small proportion of people who could still get infected with severe Covid-19.
These would include those who are not eligible or do not want to get vaccinated against Covid-19.
Professor Dale Fisher, an infectious disease expert from at the National University of Singapore (NUS) Yong Loo Lin School of Medicine, said: “Treatment of Covid is critical because the vaccine is not 100 per cent. Some will always refuse vaccination and, on occasion, a vaccinated person could get sick. That’s expected so we want the best options found and available.”
TRIALS OF COVID-19 DRUGS
The largest of the trials, involving more than 12,000 patients, is being conducted at Oxford University in the United Kingdom.
Since March last year, the Recovery trial has studied several drugs for their efficacy in treating Covid-19 patients who fall ill.
Some have got the thumbs down such as the anti-malaria drug hydroxychloroquine, which made headlines last year when it was promoted as a potential treatment for the coronavirus by Donald Trump, who was then the United States president.
However, others such as the cheap steroid dexamethasone and the arthritis drug tocilizumab have been found by the UK scientists to be effective in treating patients afflicted with Covid-19 — and have saved lives as Britain battled major outbreaks of the coronavirus there.
THE LATEST DEVELOPMENTS IN SINGAPORE
In Singapore, the Health Science Authority (HSA) last week granted interim authorisation for the antibody drug sotrovimab, which was developed by pharmaceutical company GlaxoSmithKline and immunology company Vir Biotechnology, and used to treat patients above age 18 who have mild to moderate Covid-19.
These are patients who do not require supplemental oxygen, but are at risk of becoming more ill with severe forms of the disease.
In response to TODAY’s queries, the Ministry of Health said that the drug will be available at healthcare institutions by September, barring any unforeseen delays in delivery.
The drug is based on monoclonal antibodies, which have been described as laboratory-made proteins that mimic the immune system’s ability to ward off harmful antigens such as viruses.
Singapore is also looking at another monoclonal antibody treatment by Regeneron Pharmaceutical, which will likely be used here once it is available, the National Centre for Infectious Diseases (NCID) told The Straits Times on Friday (July 9).
The antibody cocktail was used to treat Mr Trump after he tested positive for the disease in October last year and was also given a tick of approval by the UK scientists involved in the Recovery trial.
WHAT INFECTIOUS DISEASE EXPERTS HERE SAY
Infectious disease experts interviewed by TODAY said that much progress has been made in the short 18 months since the start of the pandemic when there were no known effective treatments for those struck down by the disease.
Associate Professor Sophia Archuleta, an infectious disease expert at the National University Hospital, said that the main difference between then and now is that doctors are no longer operating in an “evidence vacuum”, where drugs used at the start of the crisis were chosen based on theoretical benefit.
She cited the examples of hydroxychloroquine and antiretroviral drugs such as lopinavir-ritonavir — usually used to treat the human immunodeficiency virus (HIV). Both treatments showed no benefit when studied properly in clinical trials, Assoc Prof Archuleta said.
Professor Hsu Li Yang, who heads the infectious diseases programme at Saw Swee Hock School of Public Health at NUS, said that this progress was partly made possible by the establishment of large, single and multi-country platform trials such as the UK’s Recovery trial and the World Health Organization’s Solidarity trial.
These trials, where multiple treatments are compared simultaneously using a standardised protocol, have enabled more rapid and rigorous testing of drugs that have been developed or repurposed, and have helped eliminate drugs that were later found to be less effective, he added.
Prof Archuleta said that the existing Covid-19 therapies fall into two broad categories — those that target the virus itself (for example, antiviral drugs and monoclonal antibodies) and those that treat the body’s inflammatory response (for example, steroid treatments and immune modulators)
Prof Fisher from NUS Yong Loo Lin School of Medicine said that so far, corticosteroids — anti-inflammatory drugs — have the best evidence in improving clinical outcomes by preventing deaths and the development of severe disease.
He added that monoclonal antibody drugs, such as sotromivab, are emerging as useful treatments for patients who have mild Covid-19 but are at risk of suffering a more severe form of the disease.
WHAT SINGAPORE HOSPITALS ARE DOING
NCID has published treatment guidelines for Covid-19, which apply to all hospitals in Singapore.
Last updated on June 14, the document provides updated interim evidence-based recommendations for the therapeutic management of patients with Covid-19 in Singapore.
Explaining how the guidelines work, Dr Shawn Vasoo, NCID’s clinical director, said that generally, doctors would first consider if patients have severe Covid-19 or not.
Elaborating, Dr Raymond Fong, chief and senior consultant of Changi General Hospital’s department of infectious diseases, said that patients diagnosed with Covid-19 are evaluated and classified into four broad categories of disease severity:
- Asymptomatic: Patients who have no symptoms or do not require treatment
- Mild: Those who have acute respiratory infection symptoms with no suggestion of pneumonia
- Moderate: Patients with pneumonia but do not require supplemental oxygen therapy
- Severe or critical: Patients who have pneumonia and require oxygen therapy, and may need support under intensive care
Dr Vasoo said that for selected patients who are in the first week of illness, but are at risk of developing severe Covid-19, the anti-viral drug remdesivir may be used to hasten the recovery time.
Some high-risk patients who are not yet on oxygen support and are still in the early stage of illness may also be given remdesivir.
When they become available, monoclonal antibodies will also form part of the recommended treatments for early and non-severe Covid-19 in high-risk patients, Dr Vasoo said.
For patients who have severe Covid-19, corticosteroids such as dexamethasone are used because they have been shown to lower death rates.
This is because these patients, who require oxygen support, often have hyper inflammation, where an over-enthusiastic immune response to the virus may damage organs and in particular, the lungs, Dr Vasoo said.
Other anti-inflammatory drugs — such as tocilizumab and baricitinib (used for the treatment of rheumatoid arthritis) — are usually given in addition to corticosteroids.
These drugs are used to support the immune system by modifying its response to a threat, such as the Sars-Cov-2 virus in the case of Covid-19, Dr Fong from Changi General Hospital said.
The drugs that NCID does not recommend for treatment of Covid-19 patients include hydroxychloroquine, HIV drugs lopinavir-ritonavir, and anti-parasite drug ivermectin.
HOW MUCH HAVE OUTCOMES IMPROVED
When asked how much the progress of Covid-19 treatments have helped improve clinical outcomes in Covid-19 patients here, Dr Vasoo said that treatments along with supportive care have helped to contribute to the low mortality rate in Singapore.
However, he noted that these outcomes are not part of a clinical trial, where the impact of specific Covid-19 treatments on patients can be compared quantifiably with those who did not receive treatments.
Prof Fisher said that the biggest driver of poor outcomes globally continues to be overwhelmed hospitals with stretched resources such as beds, ventilators and oxygen.
“When all these basics remain available, we are even more enabled to save lives with the clinical skills and techniques we have learned and the drugs we now have available,” he added.