Will Covid-19 drugs be less effective against the Omicron variant?

It is not likely that members of the public will be able to soon go to the GP to get a pill when they become sick with Covid-19. PHOTO: REUTERS

SINGAPORE - As the highly mutated Omicron coronavirus variant surfaces in more places around the world, there is concern that it will evade a class of drugs - known as monoclonal antibodies - that can help prevent a person from becoming very ill with Covid-19.

These monoclonal antibodies - laboratory-made versions of the antibodies produced by the body to fight Covid-19 - are designed to look for the spike protein of the coronavirus.

"Drugs that are antibody-based, such as Regeneron's and Eli Lilly's antibody cocktails, will be affected as these target the spike protein of the virus where the majority of mutations are found," said Associate Professor Hsu Li Yang, an infectious diseases expert at the National University of Singapore's Saw Swee Hock School of Public Health.

It is unlikely that the mutations in the Omicron variant will affect the effectiveness of drugs that are not monoclonal antibodies or antibody cocktails, he added.

Associate Professor Luo Dahai from Nanyang Technological University's Lee Kong Chian School of Medicine said the mutations found in Omicron mainly focus on the virus surface's spike proteins, which may thus make the spike protein-targeting antibodies less effective.

At Alexandra Hospital, Dr Louisa Sun, an infectious diseases consultant, said the main concern where drugs are concerned is monoclonal antibodies, as most other Covid-19 treatments do not target the virus.

Still, doctors and public health experts are watching closely to see whether Omicron will affect vaccine effectiveness and cause more severe disease and deaths, she said.

Currently, the commonly used drugs for Covid-19 fall under three main categories - antibody treatments, anti-inflammatory drugs and antivirals.

Antibody treatments

Antibody treatments can block the coronavirus from entering human cells and neutralise it. The treatments are derived from convalescent plasma, which is taken from survivors' blood plasma or monoclonal antibodies such as Regen-Cov, a combination of two monoclonal antibodies produced by Regeneron Pharmaceuticals, and Sotrovimab by GlaxoSmithKline (GSK) and Vir Biotechnology.

Monoclonal antibodies are given to patients early in the course of illness.

"These are injectable drugs and are costly as their production process is complex," said Dr Sun.

A patient receiving monoclonal antibody therapy in Anchorage, Alaska, on Oct 30, 2021. PHOTO: NYTIMES

Patients need to be carefully screened for their suitability to receive monoclonal antibodies, because "if given too late or to unsuitable patients, they have no benefit", she said, and may cause harm instead.

Most people who have Covid-19 have mild symptoms or are asymptomatic and do not require specific treatment, particularly if they have been vaccinated against the virus. But there are those with mild symptoms who may have underlying conditions, such as obesity, unmanaged diabetes and cancer, that can put them at risk of severe disease.

Omicron's impact: Antibody treatments may be less potent as these target the spike protein of the coronavirus. Regeneron has said its antibody cocktail may be less effective against Omicron, while GSK said lab tests showed that its antibody drug works against the new variant.

Regeneron has said its antibody cocktail may be less effective against the Omicron variant. PHOTO: REUTERS

Anti-inflammatory drugs

Anti-inflammatory drugs are used to calm the immune system's violent reactions to the virus in the sickest patients.

The most important and commonly used drugs for Covid-19 patients who need oxygen or are in the intensive care unit are steroids, said Dr Sun.

Very common and inexpensive, steroids are used for a myriad of other medical conditions.

The main purpose is to reduce inflammation, but they are not recommended for mildly ill patients who do not need oxygen, she added. This is because "studies have not shown any benefits and instead patients may suffer from harmful side effects of steroid use, including other secondary infections and elevated blood sugar".

Dexamethasone was the first steroid found to be effective in reducing deaths from Covid-19. Apart from steroids, there are a few other drugs used to suppress inflammation, and they are known collectively as immunomodulators.

When deciding which drugs are suitable, doctors will also need to consider the patient's underlying conditions and other complications, said Dr Sun.

Omicron's impact: "Drugs that target the immune system, such as tocilizumab or dexamethasone, do not target the virus at all and therefore are unaffected by viral mutation," said Prof Hsu.

Antiviral drugs

Antiviral drugs prevent the coronavirus from multiplying inside the body.

There is remdesivir, which can be added to steroids to treat very ill patients. It is a lot more costly than steroids.

There are also the newer oral antivirals, such as molnupiravir from Merck and paxlovid from Pfizer.

Dr Sun said these drugs, similar to monoclonal antibodies, are given early to patients when they still have mild disease. "However, there are still several unknowns at this point as well, and due to various side effects, there will still be subgroups of patients who will not be able to receive these treatments," she added.

Singapore has signed an agreement to buy molnupiravir, and said in October that the antiviral pill will be available once it is approved by the Health Sciences Authority.

But will members of the public be able to soon go to the GP to get a pill when they become sick with Covid-19? Prof Hsu said this will not be likely over the next few years.

It hinges on when the professional bodies are satisfied that such drugs can be prescribed by family practitioners, as well as whether prices are low enough that general practitioner clinics will be prepared to stock and dispense them, and if patients are similarly willing to pay for them at the clinic, he said.

These drugs are not cheap. Prof Luo said: "Most of the new drugs are expensive as the pharmaceutical companies want to make a profit, from hundreds to thousands of dollars."

At the National Centre for Infectious Diseases, clinical director Shawn Vasoo said the centre is anticipating further data for the newer oral antivirals, which have been reported to have a role in mild to moderate Covid-19, and decrease progression to severe disease.

He added that the antivirals could benefit those who are at higher risk, and these are the patients currently being cared for at Covid-19 treatment facilities or in hospital.

Omicron's impact: Drugs that specifically target the virus, such as Gilead's remdesivir, Merck's molnupravir and Pfizer's paxlovid, zero in on parts of the virus that still remain conserved in current Covid-19 variants, said Prof Hsu.

Prof Luo said that while more research is needed to confirm that Omicron will not reduce the efficacy of antivirals, these drugs target the viral replicative proteins "which seem not to carry any critical mutations".

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