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The main factor in poor outcomes globally has been overwhelmed hospitals without enough beds, ventilators and oxygen. Photo: AFP

ExplainerWhich drugs are most effective to treat Covid-19 patients?

  • Vaccination remains a key priority for many countries but infectious disease experts say effective Covid-19 treatments will still be necessary
  • Several large-scale clinical trials are still under way around the globe to assess and determine the most promising medications

As nations around the world race to vaccinate citizens against Covid-19, medical experts are still working to identify the best treatments for those who become ill.

Several large-scale clinical trials are still under way 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.

Why treatments are needed

Vaccination remains a key priority for many countries in managing and reopening after the pandemic, but infectious disease experts believe effective Covid-19 treatments will still be necessary for patients who become infected. These will include those who are not eligible or do not want to get vaccinated against Covid-19.

“Treatment of Covid is critical because the vaccine is not 100 per cent,” said Professor Dale Fisher, an infectious disease expert from the National University of Singapore (NUS) Yong Loo Lin School of Medicine. “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. Since March 2020, the Recovery trial has studied several drugs for their efficacy in treating Covid-19 patients.

Some drugs have been shown to be ineffective, such as the anti-malaria drug hydroxychloroquine, which was promoted as a potential treatment by former US president Donald Trump.
However, others such as the cheap steroid dexamethasone and the arthritis drug tocilizumab have been effective in treating patients, and have saved lives as Britain battled major outbreaks.

Latest developments in Singapore

In Singapore, the Health Science Authority last week granted interim authorisation for the antibody drug sotrovimab, which was developed by pharmaceutical company GlaxoSmithKline and immunology company Vir Biotechnology, and was used to treat patients aged 18 and over with mild or moderate Covid-19. These patients do not require supplemental oxygen but are at risk of developing more severe symptoms.

The Ministry of Health said the drug will be available at health care institutions by September, barring unforeseen delays.

The drug is based on monoclonal antibodies, which are laboratory-made proteins that mimic the immune system’s ability to ward off harmful antigens such as viruses.

Singapore is also considering another monoclonal antibody treatment by Regeneron Pharmaceutical, the National Centre for Infectious Diseases (NCID) told The Straits Times last week.

The antibody cocktail was used to treat Trump after he tested positive for the disease in October last year and was also approved by the UK scientists conducting the Recovery trial.

What the experts say

Infectious disease experts said progress has been made since the start of the pandemic when there were no known effective treatments for those infected.

Associate professor Sophia Archuleta, an infectious disease expert at the National University Hospital, said doctors are no longer operating in an “evidence vacuum”, when drugs were selected based on theoretical benefit.

She cited hydroxychloroquine and antiretroviral drugs such as lopinavir-ritonavir – usually used to treat HIV. Both treatments showed no benefit during clinical trials, Archuleta said.

Professor Hsu Li Yang, who leads the infectious diseases programme at Saw Swee Hock School of Public Health at NUS, said this progress was made possible by large, single and multi-country platform trials such as the UK’s Recovery trial and the World Health Organization’s Solidarity trial.

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These trials, where multiple treatments were compared simultaneously using a standardised protocol, have enabled more rapid and rigorous testing of drugs that have been developed or repurposed, helping eliminate drugs that were later found to be less effective.

Archuleta said existing Covid-19 therapies fall into two categories: those that target the virus itself (including antiviral drugs and monoclonal antibodies) and those that treat the body’s inflammatory response (including steroid treatments and immune modulators).

Fisher from NUS said corticosteroids – anti-inflammatory drugs – have produced the best results in improving clinical outcomes by preventing deaths and the development of severe disease. He added that monoclonal antibody drugs, such as sotromivab, have emerged as useful treatments for patients with mild Covid-19 but are at risk of developing more severe symptoms.

What Singapore’s hospitals are doing

NCID has published treatment guidelines for Covid-19, which apply to all hospitals in Singapore.

The document provides recommendations for the therapeutic management of patients with Covid-19 in Singapore.

Dr Shawn Vasoo from NCID said doctors would first consider whether patients have severe Covid-19 or not.

Dr Raymond Fong, chief and senior consultant of Changi General Hospital’s department of infectious diseases, said patients diagnosed with Covid-19 were evaluated and classified into four categories of disease severity:

Asymptomatic: patients with no symptoms or who do not require treatment

Mild: those with acute respiratory infection symptoms but 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

Vasoo said that for selected patients in the first week of illness but who are at risk of developing severe Covid-19, the antiviral drug remdesivir may be used to speed recovery. Some high-risk patients not yet on oxygen support and 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, Vasoo said.

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For patients with severe Covid-19, corticosteroids such as dexamethasone have been used. This is because these patients, who require oxygen support, often have hyper inflammation, where an aggressive immune response to the virus may damage organs, particularly the lungs, 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, Fong from Changi General Hospital said.

The drugs that NCID does not recommend for treatment of Covid-19 patients include hydroxychloroquine, HIV drug lopinavir-ritonavir and anti-parasite drug ivermectin.

How much have outcomes improved

Vasoo said that treatments along with supportive care have contributed to Singapore’s low mortality rate. However, he said 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.

Fisher said the biggest driver of poor outcomes globally has been overwhelmed hospitals without enough 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 said.

Read the original article at Today Online.