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COVID-19 Updates
Lindee Abe, APRN
COVID-19 updates are a constantly evolving topic in medicine since the beginning of the pandemic. We have been building the plane while flying it since it first started. Thankfully, we now understand the disease process better and also how to treat it effectively. There have been many changes to treatment options. With the upcoming cold and flu season, now is a great time to review what is available to treat SARS-CoV-2.
We now have a better understanding of the pathology of COVID-19, which will help us understand which treatments are most effective based on where the patient is in the disease process. Initially, the progression of COVID-19 is based on the replication of SARS-CoV-2. COVID-19 is driven by an immune/inflammatory response that causes tissue damage as the disease progresses.
Inpatient versus Outpatient
There are two pathways to managing patients with COVID-19: inpatient and outpatient. Now, the majority of patients can be appropriately managed in the outpatient setting. Therefore, each patient should be assessed for need of an inpatient admission based on the severity of symptoms and the risk of disease progression. See the list below of the comorbidities that the CDC considers risk factors for progression to severe COVID-19:
- Age ≥65 years
- Asthma
- Cancer
- Cerebrovascular disease
- Children with certain underlying conditions
- Chronic kidney disease
- Chronic lung disease (interstitial lung disease, pulmonary embolism, pulmonary hypertension, bronchiectasis, COPD)
- Chronic liver disease (cirrhosis, non-alcoholic fatty liver disease, alcoholic liver disease, autoimmune hepatitis)
- Cystic fibrosis
- Diabetes mellitus, type 1 and type 2
- Disabilities
- ADHD
- Cerebral palsy
- Congenital malformations
- Limitations with selfcare or activities of daily living
- Intellectual and developmental disabilities
- Learning disabilities
- Spinal cord injuries
- Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
- HIV
- Mental health disorders (mood disorders including depression, schizophrenia spectrum disorders)
- Neurologic conditions (dementia)
- Obesity (BMI ≥30 kg/m2) and overweight (BMI 25 to 29 kg/m2), or ≥95th percentile in children
- Physical inactivity
- Pregnancy or recent pregnancy
- Primary immunodeficiencies
- Smoking (current and former)
- Sickle cell disease or thalassemia
- Solid organ or blood stem cell transplantation
- Substance use disorders
- Tuberculosis
- Use of corticosteroids or other immunosuppressive medications
Outpatient therapy for COVID-19 is appropriate for those who are symptomatic with mild to moderate COVID-19 and are at an increased risk of progression due to the above risk factors. There is also a simplified way to assess the need for outpatient therapy by identifying if the patient is≥65 years of age, immunocompromised, risk factors, ≥50 years of age, and not vaccinated (have not received any vaccination).
Therapy
The therapy is based on the duration of symptoms in patients who are candidates for outpatient therapy. If the patient has symptoms for less than five days, the nirmatrelvir/ritonavir (Paxlovid) is the treatment of choice:
In patients that have symptoms for 6-8 days, remdesivir (≤ 7 days) or convalescent plasma (≤ 8 days) are the treatment of choice. Likewise, supportive care is the treatment of choice in patients with symptoms >8 days. Remember that the first day of symptoms is counted as day one, not day 0, as some patients think. Nirmatrelvir/ritonavir (Paxlovid) is the most commonly prescribed medication for COVID-19. Therefore, the rest of this post will focus on the prescribing of this therapy specifically.
Paxlovid
Initially, nirmatrelvir/ritonavir (Paxlovid) had emergency use authorization only. In May 2023, the FDA approved nirmatrelvir/ritonavir (Paxlovid) for treating mild-to-moderate COVID19 patients at high risk for progression to severe COVID-19. Nirmatrelvir/ritonavir (Paxlovid) is still not authorized to treat inpatient severe COVID-19, preexposure or post-exposure prophylaxis, or for use longer than five days. Nirmatrelvir/ritonavir (Paxlovid) is approved for patients 12 years of age and older.
According to the FDA, nirmatrelvir/ritonavir (Paxlovid) is effective for patients where treatment is indicated. Specifically, nirmatrelvir/ritonavir (Paxlovid) reduced the number of people needing hospitalization or death from COVID-19 by 86% compared to those who did not receive treatment. Also, there were no patient deaths from COVID-19 in the 24 weeks after infection, but the group not receiving treatment had 15 patients who died during that same 24-week period.
Dosing
The dosing of nirmatrelvir/ritonavir (Paxlovid) is also based on renal function. Patients with an eGFR ≥60 mL/min should be prescribed nirmatrelvir 300 mg-ritonavir 100mg twice daily for five days. Those with an eGFR of 30-59 mL/min should be prescribed nirmatrelvir 150 mg ritonavir 100mg twice daily for five days. Patients with eGFR < 30 mL/min are not recommended to receive nirmatrelvir/ritonavir (Paxlovid) based on the manufacturer’s guidelines. However, patients without a suspected kidney impairment who don’t have a recent eGFR can have nirmatrelvir/ritonavir (Paxlovid) prescribed without checking a creatinine level. Personally, if a patient doesn’t have a recent eGFR when they are seen for suspected CVOID-19, I will order a BMP at the same time as the COVID-19 test if they are a candidate for nirmatrelvir/ritonavir (Paxlovid).
Drug Interactions
One major consideration with nirmatrelvir/ritonavir (Paxlovid) is the drug interactions that occur with the medication because it is a CYP3A inhibitor. I always check the patient medication list before prescribing nirmatrelvir/ritonavir (Paxlovid), and if there are questions about interactions, the pharmacy is a great resource. Some of the more frequent ones that I have seen are statins, which also could be held and restarted three days after the completion of therapy.
Concomitant Dose Reduction
Other medications could have the dose reduced while taking nirmatrelvir/ritonavir (Paxlovid). Some medications should also not be administered with nirmatrelvir/ritonavir (Paxlovid), and alternative therapies should be considered. Other medications that are known to interact with nirmatrelvir/ritonavir (Paxlovid) and would necessitate an alternative therapy include:
- Cardiovascular medications (amiodarone, clopidogrel, quinidine, propafenone, ivabradine, flecainide, dronedarone, dofetilide, disopyramide)
- Pulmonary hypertension medications (e.g., sildenafil, tadalfil, vardenafil)
- Neuropsychotic agents (e.g., clozapine, lurasidone, midazolam, pimozide)
- Immunosuppresants (e.g., voclosporin)
- Anti-infectives (e.g., glecaprevir/pibrentasvir, rifampin, rifapentine)
- Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin, primidone)
- Miscellaneous medications (e.g., bosentan, certain chemotherapeutic agents, ergot derivatives, lumacroftor/ivacaftor, St. John’s wort, tolvaptan)
The National Institute of Health (NIH) has a great resource that lists medications with interactions and specifies which other medications can be held during therapy and which ones may benefit from a reduced dose.
Rebound Symptoms
Rebound Symptoms are a point of education that I would like to discuss with all patients being prescribed nirmatrelvir/ritonavir (Paxlovid). The EPIC-HR and EPIC-SR trials found that this occurred at similar rates between patients who received nirmatrelvir/ritonavir (Paxlovid) and also patients in the placebo group. I have found in practice that this does occur frequently and therefore I feel that this is important to discuss with patients. If it is not discussed, there are many phone calls and repeat visits when the medication is completed, and the patient may suddenly feel worse. While it may occur at similar rates to patients who don’t receive medication, it can be unexpected when given a medication that patients believe should resolve their symptoms.
Lageviro
Additional outpatient treatment includes molnupiravir (Lageviro), although the reduction in hospitalization is only 30%, much less than nirmatrelvir/ritonavir (Paxlovid). Molnupiravir (Lageviro) does not require dose adjustment for renal or liver disease, which is also an advantage of the medication. However, Molnupiravir (Lageviro) requires post-use contraception and should not be used in pregnancy. This topic requires more patient education and reassurance that the patient will comply with the education.
Nirmatrelvir/ritonavir (Paxlovid) has been approved for use by the FDA and is an important tool for treating COVID-19. The appropriate selection of the right patient to receive the treatment and weighing the impact of the patient’s current medications are essential to the prescribing of nirmatrelvir/ritonavir (Paxlovid). Shared decision-making remains central to achieving optimal patient outcomes for the treatment of CVOID-19.
References:
Cohen P, Gebo K. COVID-19: managing adults with acute illness in the outpatient setting. Post TW, ed. UpToDate. UpToDate Inc. Accessed October 10, 2023. https://www.uptodate.com/contents/covid-19-management-of-adults-with-acute-illness-in-theoutpatient-setting
National Institute of Health. COVID-19 Treatment Guidelines. 21 July 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals-includingantibody-products/ritonavir-boosted-nirmatrelvir–paxlovid-/paxlovid-drug-druginteractions/
U.S. Food & Drug Administration. Frequently asked questions on the emergency use authorization for Paxlovid for treatment of COVID19. https://www.fda.gov/media/155052/download
