COVID Therapeutics

It’s been a long 3 years of constant changes with COVID. Most people are tired of hearing about it – especially patients and clinicians. While we seem to be at a point where cases aren’t as frequent or as severe, more “surges” are likely. With this in mind, now is the ideal time to provide an update on what is available for treatment.

Home Management of COVID

In the outpatient setting the primary treatment for COVID-19 was symptomatic over-the-counter treatment initially for infection. In many cases, this treatment plan remains the same. Ibuprofen and/or acetaminophen for fever, chills, and myalgias. Increased fluid intake for dehydration. Patients should be encouraged to get rest and sleep. The same symptomatic treatments we do for most viral illnesses in the clinic. Depending on the variant, cough is one of the most bothersome complaints for many patients. Unfortunately, I have not found cough is especially hard to treat with both over-the-counter and prescription medications. The common piece of education I give patients is to try a humidifier at night. I also tell them that the cough will be the last symptom to resolve usually. This helps manage expectations for the patient to a prevent return visit with the complaint that they are still coughing.

COVID Pharmacotherapy

Options for COVID therapeutics are increasing. There are now antivirals available for treatment of COVID-19. The National Institute of Health is an excellent resource for the most up-to-date COVID-19 treatment guidelines. The first thing to consider is the current supply of antivirals. It was only several months ago that we lacked the supply to be able to treat every patient and had to prioritize the patients that would be afforded the most benefit from the antiviral. Luckily, that is not currently the case and the current recommendation is that antiviral therapy should be offered to all patients that are outpatient and not requiring oxygen.

My personal experience when considering antiviral therapy is the recommended time frame from onset of symptoms to confirmed positive test is often a barrier to being within the window where antiviral therapy is appropriate. Most patients come in after several days of symptoms when they realize that this may not be a cold. One facility I work in doesn’t have rapid or point-of-care testing, so the PCR takes 24-48 hours to be resulted. The patient is then outside of the window for treatment with an antiviral, which can range from 5-7 days depending on the medication.

Nirmatrelvir

Assuming the patient is a candidate for antiviral therapy, what are the options? The primary medication I have seen used most frequently is ritonavir-booster nirmatrelvir. The first thing to know about this medication is that it is only recommended at 5 days or less after symptom onset. The second very important consideration in prescribing ritonavir-booster nirmatrelvir is that there is alternate dosing if a patient has impaired renal function, specifically an eGFR ≤60.

Like other antiviral COVID therapeutics, Ritonavir-booster nirmatrelvir is also contraindicated with severe liver impairment or an eGFR ≤30. This can be a fairly common issue, especially several months ago when we only had enough ritonavir booster nirmatrelvir to treat Higher risk patients. During that time the patients that had comorbidities were usually the patients that I would be concerned with impaired kidney function, but then frequently didn’t have recent lab work to review. This resulted in a lab draw being added and results not typically being available until the next day, which delayed the initiation of the antiviral (if the patient had a point-of-care or at-home test that was positive already). Another practice pearl is that point-of-care and at-home tests are sufficient to start antiviral therapy. There is no reason to delay starting an antiviral for confirmatory testing with a PCR test.

As for age restrictions, ritonavir-booster nirmatrelvir is only recommended for patients over 12 years and at least 40 kg. Ritonavir-booster nirmatrelvir hasn’t been sufficiently studied in pregnant patients. Pregnancy can increase the risk of severe COVID-19 disease. The best solution would be to have a discussion with the patient’s OB/GYN for their recommendation.

Education about nirmatrelvir

Patient education with ritonavir-booster nirmatrelvir is also very important. Patients can have a rebound of symptoms after completion of ritonavir-booster nirmatrelvir. If patients aren’t aware of this, they think they may have been reinfected with COVID or have a secondary infection. Ritonavir-booster nirmatrelvir also interacts with numerous medications, as ritonavir is a cytrochrome P450 inhibitor. The recommendations can be looked up on the National Institute of health website that has recommendations on when to withhold medications, prescribe alternate agent, or monitor for side effects. The most common interaction I have found with COVID therapeutics is with statin medications, in which case the patient can stop statin medication while taking ritonavir-booster nirmatrelvir.

Molnupiravir

Another antiviral option for treatment is molnupiravir. Like ritonavir-booster nirmatrelvir, it is recommended only in the first 5 days after symptoms onset. Molnupiravir is recommended if there is a contraindication to ritonavir-booster nirmatrelvir. Molnupiravir is not recommended under the age of 18 or in pregnancy. Molmupiravir can also cause rebound symptoms and patients should be educated regarding this possibility. There is the recommendation from the National Institute of Health that backup contraception should be used during and following use of molnupiravir. Molnupiravir does not have dosing adjustment required for hepatic or kidney impairment like ritonavir-booster nirmatrelvir.

Other Antivirals

There are two additional anti-viral COVID therapeutics noted by the National Institute of Health for treatment of outpatient COVID-19, remdesivir and Bebtelovimab. However, both medications are available through IV only. This limits the use of these medications and although they were used more initially, I have not seen them utilized recently.

Additional Therapy

The National Institute of Health had specific recommendations for the outpatient treatment of COVID-19, but also had treatments that were specifically not recommended. The first treatment not recommended in the outpatient setting is dexamethasone. Dexamethasone is used successfully in the inpatient setting with patients requiring oxygen therapy, but has been shown to worsen outpatient outcomes. The National Institute of Health also recommends against the use of Ivermectin, chloroquine, azithromycin, doxycycline, hydroxychloroquine, and HIV protease inhibitors. It is promising that we do have oral treatment options now in the outpatient setting.

One more point I would emphasize is the importance of having the conversation with the patient that both ritonavir-booster nirmatrelvir and molnupiravir only have the FDA emergency authorization use approval at this time. This may change in the future, but I think it is an important conversation to have with patient in order to make informed decisions.

Summary

While there is ongoing research for additional COVID therapeutics that seems to never end, it will hopefully result in better data regarding treatment and more treatment options. As recently as a year ago, it was difficult to tell patients that we didn’t have any options for treatment or the options we did have were difficult to get scheduled. While the options we have now are still under an emergency use authorization from the FDA, we can at least have the conversation with patients about the treatments available.

References:

Hughes, B., & Berghella, V. (n.d.). COVID-19: Antepartum care of pregnant patients with symptomatic infection. UpToDate. Retrieved September 25, 2022, from https://www.uptodate.com/contents/covid-19-antepartum-care-of-pregnant-patients-withsymptomatic-infection

“Paxlovid Drug-Drug Interactions.” National Institutes of Health, U.S. Department of Health and Human Services, https://www.covid19treatmentguidelines.nih.gov/therapies/antiviraltherapy/ritonavir-boosted-nirmatrelvir- paxlovid-/paxlovid-drug-drug-interactions/.

U.S. Department of Health and Human Services. (n.d.). Molnupiravir. National Institutes of Health. Retrieved September 25, 2022, from https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/molnupiravir/

U.S. Department of Health and Human Services. (n.d.). Nonhospitalized adults: Therapeutic management. National Institutes of Health. Retrieved September 25, 2022, from https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-ofadults/nonhospitalizedadults–therapeutic-management/