Antiviral Treatment For Covid-19

Introduction

Brief overview of covid-19

COVID-19 is an acute respiratory infection caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). It was declared a public health emergency of international concern in January 2020 and then a pandemic in March 2020. It can have symptoms of a mild cold illness or more severe and even become fatal, including septic shock and multiorgan failure.¹ There have been several variants, and symptoms can last longer than 12 weeks - where it becomes Long Covid.¹

Importance of antiviral treatment

Antiviral treatment can be given to people at high risk of getting seriously ill with COVID-19. For example in the UK, if they are 12 and above, have symptoms and have tested positive for COVID-19.² They are important because they can reduce the risk of being hospitalised or dying from COVID-19,³ and potentially Long Covid.¹² They must be administered between 5-7 days of having symptoms to be effective, depending on which one is given.³ Depending on your location, it will differ on how you obtain these - but it will be through a healthcare provider.^3,2

These include: 

• Paxlovid 
• Remdesivir
• Sotrovimab
• Molnupiravir²

Basics of covid-19

SARS-CoV-2 virus

Coronaviruses are enveloped RNA viruses that can cause people to be ill and include SARS and MERS. SARS-CoV-2 virus has not been detected prior to December 2019 in Wuhan, China. It is similar to other SARs like coronaviruses but still distinct and is the 7th coronavirus to infect humans. The origin is still unknown but is potentially from zoonotic origin, for example from bats in wet markets. Some studies suggest there were earlier cases than originally thought in other countries.¹

Transmission and symptoms

COVID-19 is spread primarily by respiratory, and aerosol transmission. In respiratory, small liquid particles from the nose or mouth of the infected person from coughing, sneezing, talking etc. and can be inhaled via the other person’s nose, mouth or if close enough - eyes.¹ Ventilation and proximity are the major risk factors in this transmission. Aerosols are produced in medical settings in certain procedures (aerosol-generating procedures), and potentially in certain other settings however it has not been confirmed.¹

Symptoms /diagnostic factors include:

• Fever
• Difficulty breathing
• Cough
• Headache
• Altered taste/smell
• Fatigue
• Sore throat
• Muscle aches¹

Antiviral treatment approaches

Overview of antiviral drugs

Antiviral drugs are medicines that treat viral infections. Viruses are microorganisms which cause disease and use the host's cells to replicate. Antiviral drugs stop the development of the virus, in contrast to antibiotics which destroy the bacteria. Due to them using the host cells, it is difficult to develop a safe drug without damage to them as well. There are many viral infections without effective antivirals.⁴ 

Approved antiviral drugs for covid-19 

Remdesivir

Mechanism of action

Remdesivir is a prodrug which gets metabolized in the body to its active form which binds to RNA polymerase to stop viral replication. It was originally developed for Ebola.⁵

Availability and usage guidelines

• Intravenous (IV) administration
• 200g IV on 1st day, follow up 100mg IV for up to 10 days - initiated within 10 days of symptoms
  • COVID-19 IN If immunocompromised patients are hospitalised with pneumonia 
• 200g IV on 1st day, follow up 100mg IV for up to 5 days - initiated within 10 days of symptoms
  • COVID-19 inIf patients are hospitalized with pneumonia with supplemental oxygen
• 200g IV on 1st day, follow up 100mg IV for 3 days - initiated with 7 days of symptoms
  • COVID-19 in patients without oxygen supplementation who are at higher risk of progression to severe COVID-19⁶

Adverse reactions and contraindications:

• Headache
• Nausea 
• Rash 
• Sinus bradycardia 
• Allergic reaction
• Infusion-related reaction⁶

Caution with 

• Liver and kidney impairment (do not use if glomerular filtration rate less than 30 30 mL/minute/1.73 m2)⁶

Molnupiravir

Mechanism of action

Molnupiravir is a prodrug, a compound that is biologically inactive until it is metabolized in the body to become a drug.²⁸ It gets metabolized and then is taken up by cells and a phosphate group is added. This version becomes part of the SARS-COV-2 RNA which prevents it from replicating.⁷

Availability and usage guidelines:

• Oral use in 200mg capsules
• 800mg every 12 hours 
• 5 days
• To be taken with or without food 
• No adjustments for kidney disease
• Not for use in children and adolescents⁷
• Must be taken within 5 days of symptoms³

Adverse reactions and contraindications

Adverse reactions: 

• Diarrhea
• Dizziness
• Nausea⁷

Precautions  

• Not for under 18
• Not recommended in pregnancy⁷

No contraindications or drug interactions

Paxlovid 

Mechanism of action

Made up of Nirmatrelvir and Ritonavir. Nirmatrelvir is a SARS-COV-2 protease inhibitor which prevents the virus from processing protein precursors, stopping replication. Ritonavir is an HIV (Human Immunodeficiency Virus) inhibitor which increases the levels of Nirmatrelvir but does not affect SARSCOV2.⁷ It can be taken in tablet form and has increased efficacy in clinical trials⁸

Availability and usage guidelines:

• Oral use
• Come in 150mg Nirmatrelvir and 100mg Ritonavir 
• The dose is 300mg/100mg (2 tablets Nirmatrelvir, 1 tablet Ritonavir) 
• Every 12 hours
• 5 days
• With or without food
• Ages 12 and over 
• Moderate kidney disease dose adjusted to 150mg/100mg (1 tablet Niramtrelvir, 1 tablet Ritonavir)⁷

Adverse reactions and contraindications

Adverse reactions:

• Diarrhea
• Dygueisa (metallic/rancid taste)
• Muscle aches 
• High blood pressure ⁷

Contraindications and precautions

• Only in pregnancy if monoclonal antibodies are unavailable
• Liver toxicity reported but rare 
• Not recommended in people with severe liver or kidney disease
• Potential for allergic reactions⁷
• Interacts with lots of medications³

In Paxlovid, there is Ritonavir which slows down the metabolism of the antiviral in the liver so that it can work. However, it also slows down the metabolism of multiple other drugs, meaning if the person is taking other drugs such as anticoagulants it could cause side effects of these. So it shouldn’t be given to any of the drugs included in this, people with liver or kidney impairment, and certain medicinal products which dependent on a certain liver enzyme (CYP3A) for clearance or are CYP3A inducers which may be associated with resistance.^7,8

Host-targeted therapies

Current antiviral drugs tend to target the virus itself, with viral resistance becoming more common. It is believed for COVID-19 and any potential future pandemics/epidemics, host-targeted therapies are required as well. These target the molecules in host pathways instead. Viruses usually hijack these pathways by interacting with host proteins to avoid the immune response.⁹

These include corticosteroids, such as dexamethasone and have become one of the main treatments for severe COVID-19.  Monoclonal antibody drugs have been approved for treatment, as well as cytokine antagonists such as tocilizumab.¹¹ 

Challenges and considerations

Drug resistance

Some new variants of COVID-19 could potentially become resistant to antivirals which could have public health implications. This is monitored especially in immunocompromised patients¹³ where viral mutations can happen when treated with antivirals.¹⁴

Global accessibility

There was a global divide on vaccines, called a “vaccine apartheid” ¹⁶ by the WHO Director General where high-income countries were hoarding the majority of vaccines leaving little for low-income countries¹⁷. It is happening again with antiviral treatments, with Paxlovid remaining out of reach for most middle-low income countries after it was developed. Unlike with vaccines, however, Pfizer did agree to permit generic manufacture of Paxlovid. Paxlovid must be given very soon after the start of treatments and so requires testing, which is limited in low-income countries.^{18, 19}

Future directions

Continued research and development

Stephen Griffin, a virologist from the University of Leeds, has expressed concern regarding antiviral treatment and the need for more drug combinations due to increasing resistance and contraindications of existing treatments. However, says there is no motivation for pharmaceutical companies to trial combination drugs because they have no incentive with things being pared down in terms of COVID-19.⁸ The UK’s COVID-19 antivirals and therapeutics taskforce was closed down in March 2023 in line with their “Living with Covid” strategy.³⁰ 

The antiviral Acyclovir is being trialled as a potential treatment for symptoms of Long Covid.^20,21

Public health measures and vaccination

COVID-19 is very much still present and causing detrimental effects including hospitalization, death and Long Covid, so these precautions are still recommended even though many regulations are being abandoned by countries.^{22, 23}

Masks

Masks are still advised to protect yourself and others, especially in crowded or poorly ventilated places. Different masks provide different levels of protection, with N95 masks providing a tighter fit and efficient filtration of particles.²⁹

Ventilation

Improving ventilation can reduce the gathering of virus particles in indoor spaces. Ways to do this include: 

• Meeting outdoors
• HEPA air purifiers
• Avoid crowded spaces
• Open windows 
• Changing filters in heating and HVAC systems
• Improving air flow using fans²⁴

Vaccination

COVID-19 vaccination is advised to increase your body’s protection against the virus, and even if you get the virus it will reduce the risk of hospitalization and death (CDC). It is recommended you stay up to date with them and should check online for your area’s vaccine policies.²⁵

Isolation and hygiene 

Self-isolation is recommended if you have symptoms for 10 days by WHO, testing for COVID-19 where possible and good hygiene including handwashing.^{26, 27}

Conclusion

Recap of antiviral treatments

There are multiple options for antiviral treatments depending on clinical assessment by health professionals. This includes Remdesivir, Molu]nupiravir, and Paxlovid as well as host targeted therapies such as corticosteroids.

Importance of a comprehensive approach to managing covid-19

The risk of death, hospitalisation and Long Covid has been found to increase with repeated infection.²⁷ Therefore, it is essential to try and avoid infection with COVID-19 with public health measures, as well as utilizing antivirals when clinically necessary. One or the other is not enough, for example, just getting the vaccine and not taking other precautions such as wearing masks, ventilation and isolating. It requires a comprehensive approach.

FAQs

What is the most effective antiviral for covid-19?

It is case-dependent and will be assessed by medical professionals.

Who qualifies for antiviral treatment for covid?

It depends on your location, but people who are at high risk of getting seriously ill with COVID-19. For example in the UK, if they are at high risk, are 12 and above, have symptoms and have tested positive for COVID-19

Is it worth taking covid antivirals?

It is worth taking COVID antivirals if it is clinically indicated as it can reduce the risk of death and long covid.

How long do you take covid antivirals for?

Usually 5 -7 days depending on the type of antiviral.