Long COVID: how personalized medication optimization can support recovery

Most people recover from COVID-19 within a few weeks, but some continue to feel unwell for months or even years. This is known as long COVID. There is no single medication that cures it, so treatment focuses on relieving symptoms, and many people end up taking several medications at once. This article explains what long COVID is, which medications are commonly used to manage its symptoms, and how pharmacogenetic testing can help you and your healthcare providers choose medications and doses that are safer and more likely to work.

What is long COVID?

The World Health Organization defines long COVID (post-COVID-19 condition) as symptoms that usually start within 3 months of a COVID-19 infection, last for at least 2 months and cannot be explained by another diagnosis. In 2024, the US National Academies of Sciences, Engineering, and Medicine described long COVID as a chronic condition that follows a COVID-19 infection and lasts for at least 3 months.

Long COVID can affect almost any part of the body. More than 200 symptoms have been reported. The most common include:

• tiredness (fatigue), often worse after physical or mental effort;
• shortness of breath and cough;
• a racing heart, chest pain or dizziness when standing up;
• trouble thinking, concentrating or remembering ("brain fog");
• headaches, muscle and joint pain;
• poor sleep, depression and anxiety.

How common is long COVID?

Estimates vary with how long COVID is defined and measured. A global analysis published in JAMA estimated that about 6% of people who had a symptomatic COVID-19 infection in 2020 and 2021 still had fatigue, breathing problems or thinking problems 3 months later. Other reviews suggest that long COVID follows at least 10% of infections. Long COVID can affect people of all ages, including those who had a mild infection.

Can COVID-19 affect the heart in young people?

COVID-19 can cause inflammation of the heart muscle (myocarditis), but this is uncommon. In a registry of 1,597 college athletes in the United States who had COVID-19, 2.3% showed signs of myocarditis on heart imaging, and most of them had no heart symptoms. In children, a rare but serious reaction called multisystem inflammatory syndrome in children (MIS-C) can occur a few weeks after infection. Anyone who has chest pain, palpitations or shortness of breath after COVID-19 should have their heart checked.

Can COVID-19 vaccines cause complications?

Like all medications, COVID-19 vaccines can cause side effects. Most are mild and pass within a few days, such as a sore arm, fever, headache or tiredness. Rare but serious complications have also been reported. The best known is inflammation of the heart muscle (myocarditis) after mRNA vaccines. In a large Israeli study of more than 2.5 million people vaccinated with the Pfizer-BioNTech vaccine, myocarditis occurred in about 2 in 100,000 people, and in about 11 in 100,000 young men aged 16 to 29. Most cases were mild or moderate. Some people also report long-lasting symptoms after vaccination that resemble long COVID, and this is still being studied.

The two mRNA vaccines may not have the same effects. A statewide study in Florida compared adults who received a first dose of either the Pfizer-BioNTech or the Moderna vaccine between December 2020 and August 2021. Over the next 12 months, people who received the Pfizer-BioNTech vaccine had a higher risk of death from any cause, including heart-related deaths, than matched people who received the Moderna vaccine. This was an observational study that compared the two vaccines with each other, not with unvaccinated people, so it cannot prove that the vaccine caused the difference.

At the same time, observational studies suggest that people who were vaccinated before a COVID-19 infection were less likely to develop long COVID, although the certainty of this evidence is low. If you have had a reaction to a vaccine, or you are unsure whether a vaccine is right for you, talk to your healthcare provider about your personal benefits and risks.

How is long COVID treated?

There is no approved medication that cures long COVID. Antiviral treatment has been tested: in a randomized trial of people who had long COVID symptoms for 3 months or longer, a 15-day course of nirmatrelvir-ritonavir (Paxlovid) did not improve symptoms compared with placebo.

Care therefore focuses on each person's symptoms and on rehabilitation. This can include pacing activities to avoid crashes after exertion, breathing exercises, sleep support, and treatment of mental health problems. Medications are often part of the plan, and because people with long COVID may have several symptoms at once, they are often prescribed several medications at the same time. The more medications a person takes, the greater the risk of side effects and drug interactions.

Which long COVID medications are affected by genes?

Many medications used to manage long COVID symptoms are broken down by liver enzymes, such as CYP2D6, CYP2C19 and CYP2C9, whose activity depends on your genes. Here are some examples.

Racing heart and dizziness on standing (POTS): beta-blockers, such as metoprolol or propranolol, are sometimes used to slow a racing heart. For metoprolol, the 2024 CPIC guideline for beta-blockers recommends that CYP2D6 poor metabolizers start at the lowest recommended dose, increase the dose carefully and be monitored more closely for a slow heart rate, or consider another beta-blocker. Poor metabolizers can have about five times more metoprolol in their blood than normal metabolizers given the same dose.

Depression and anxiety: antidepressants such as sertraline, escitalopram and venlafaxine are broken down by CYP2C19 and CYP2D6. The 2023 CPIC guideline recommends dose changes or a different medication for some genetic profiles. In the PRIME Care randomized trial, genetic testing helped doctors avoid antidepressants with predicted drug-gene interactions and modestly improved remission of depression. Learn more about Pillcheck for mental health and the best medication for anxiety and depression.

Pain and headaches: several NSAIDs, such as celecoxib, ibuprofen and meloxicam, are broken down by CYP2C9, and CPIC recommends lower starting doses or another medication for people with reduced CYP2C9 activity. Codeine and tramadol need CYP2D6 to work: they may give little relief in poor metabolizers and can be dangerous in ultrarapid metabolizers. Low-dose amitriptyline, used for headaches, nerve pain and sleep, is broken down by CYP2D6 and CYP2C19. Learn more in Why don't painkillers work for everyone?

Nausea: ondansetron is broken down by CYP2D6. CPIC recommends that CYP2D6 ultrarapid metabolizers use a different anti-nausea medication, because ondansetron may not work well for them.

Heartburn: proton pump inhibitors (PPIs), such as omeprazole and pantoprazole, are broken down by CYP2C19, and the dose may need to change based on your genes. Long-term PPI use has also been linked to a higher risk of some infections. Learn more in Tecta, PPIs and COVID-19 risk.

Blood clots: people who develop blood clots or have a heart problem may need blood thinners. Genes guide the dose of warfarin (CYP2C9 and VKORC1) and the choice of clopidogrel (CYP2C19).

Why does taking several medications at once matter?

Some medications block the same liver enzymes that are affected by your genes. For example, fluoxetine, paroxetine and bupropion strongly block CYP2D6. A person with normal CYP2D6 genes who takes one of them can process other CYP2D6 medications like a poor metabolizer. In the same way, a person who inherited reduced CYP2D6 activity is expected to respond as if they were already taking a CYP2D6 blocker. When several medications are combined, both genes and drug interactions need to be considered together.

How can Pillcheck help?

Pillcheck is a pharmacogenetic test that shows how your genes affect your response to medications. A Pillcheck pharmacist reviews your genetic results together with all of your current medications and supplements, checks for drug-gene and drug-drug interactions, and provides recommendations that you can share with your doctor. This can help you avoid side effects and find an effective treatment sooner while you recover from long COVID.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• Long COVID is a long-term condition that follows a COVID-19 infection and lasts at least 3 months. It can affect people of all ages.
• COVID-19 vaccines can rarely cause serious complications, such as myocarditis, and the two mRNA vaccines may differ in their effects.
• There is no single cure, so treatment focuses on symptoms such as fatigue, a racing heart, pain, poor sleep, depression and anxiety.
• Many people with long COVID take several medications at once, which increases the risk of side effects and interactions.
• Genes affect how the body handles many of these medications, including metoprolol, antidepressants, NSAIDs, codeine, tramadol, ondansetron and PPIs.
• A Pillcheck medication review considers your genes and all of your medications together.

Frequently asked questions

How long does long COVID last?

It varies. Many people improve gradually over months, but some have symptoms for a year or longer. Long COVID is defined as lasting at least 3 months after infection.

Is there a medication that cures long COVID?

No. No medication has been approved to cure long COVID. Treatment focuses on managing symptoms and rehabilitation. Talk to your healthcare provider about a plan that fits your symptoms.

Can a genetic test diagnose long COVID?

No. A pharmacogenetic test does not diagnose long COVID or any other disease. It shows how your body is likely to respond to medications, which can help your healthcare providers choose medications and doses for your symptoms.

I take several medications for long COVID. Should I have them reviewed?

Yes. Taking several medications increases the risk of side effects and interactions. Ask your pharmacist or doctor to review all of your medications, including over-the-counter medicines and supplements. A Pillcheck pharmacist reviews them together with your genetic results.

References

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