Dr. Mazade's Question of the Week: Treatment and Prevention Strategies for COVID-19 in High Risk Persons

Happy New Year!

Sweet, adorable, glasses-wearing, curious, socially smiling, six-month old former preterm infant, Danica, and her 17-year-old mother, Mitzi, visit your office for a check-up.

They are doing well. Baby Danica has chronic lung disease for which she uses bronchodilators, and has pulmonary hypertension. She is no longer on home oxygen. Her weight is up nicely since the time of her last visit when it was 3.5 kg.

Mitzi has a rheumatologic disorder, has been vaccinated for COVID-19, but takes immunosuppressants, which may have prevented her from responding well to her vaccines.

They ask you to help come up with a plan to prevent COVID-19 infection or to ameliorate disease if they develop infection. Use the table below to determine which of the following statements are true regarding treatment and prevention strategies for COVID-19 in high risk persons. More than one may be true:

A. Before prescribing Paxlovid for Mitzi for pre-hospital treatment of COVID-19 infection, it would be important to check for medication interactions with the CYP3 inhibitor, ritonavir, which is included in the co-packaging to slow the metabolism of the COVID-19 active nucleoside analog, Niraltrelvir. You take a few minutes at this time to run her list of meds and consider listing ritonavir as a medication precaution if you find an interaction.

B. Due to the concern for cartilage and bone damage, oral antiviral treatment with Molnupiravir should be avoided for pre-hospital treatment of COVID-19 in mother, Mitzi, until she is 18 years old.

C. Due to the age-restrictions of the EUA issued on December 2, 2021, only Mother Mitzi, but not Baby Danica, would be eligible for the one-time IM administration of the dual monoclonal antibody, Evusheld, which may afford some protection for 6 months.

D. At this time, Danica does not meet the age requirement for pre-hospital treatment of COVID-19 with the GSK monoclonal antibody, Sortrovimab.

Thanks for taking the time to educate yourselves!

Marc

COVID-19 Therapeutics and Preventatives

Class	Product	Dosing	Setting	Indication	Side effects	Status
Antiviral, Nucleoside analog	Remdesivir Veklury by Gilead	5 mg/kg (up to 200 mg) day 1 then 2.5 mg/kg (up to 100 mg) IV on days 2-5.	Hospital	Hypoxic COVID-19 pneumonia, not on ECMO with GFR>30	Hepatotoxicity. Must check ALT, Cr, PT	FDA approved for those 12 years and older and issued EUA for those < 12 years and 3.5 to 40 kg on 10/22/20.
Antiviral, Nucleoside analog	Remdesivir Veklury by Gilead	5 mg/kg (up to 200 mg) day 1 then 2.5 mg/kg (up to 100 mg) IV on days 2 and 3.	Non- hospital	Non-hypoxic COVID-19 infection in high risk patients¹	Hepatotoxicity. Must check ALT, Cr, PT	FDA approved for those 12 years and older and issued EUA for those <12 years and 3.5 to 40 kg on 10/22/20.
Antiviral, protease inhibitor (Mpro), a inactive HIV-1 protease (ritonavir) used to inhibit CYP3 metabolism of Mpro	Paxlovid [Nirmatrelvir (aka Mpro) and ritonavir] by Pfizer	3 co-packaged pills (two 150 mg Mpro & one 100 mg ritonavir per dose) given orally BID x 5d .	Non- hospital	Non-hypoxic COVID-19 infection in high risk patients¹	Loss of taste, diarrhea, HTN, muscle aches, liver injury, HIV resistance, Contraindicated with CY3P dependant drugs (inhibitor of CYP3).²	EUA issued for >= 12 years and 40 kg on 12/22/21.
Antiviral, Nucleoside analog	Molnupiravir By Merck	Four 200 mg capsules every 12 hours for 5 days	Non- hospital	Non-hypoxic COVID-19 infection in non-pregnant, high risk patients¹	Diarrhea, nausea and dizziness. Bone and cartilage damage. Fetal injury concerns. Birth control rec. for + 90 days (men) and bc and no breastfeeding for +4 days (women).	EUA issued for 18 years and older on 12/23/21
Monoclonal antibody	Evusheld (Tixagevimab and cilgavimab) by AstraZeneca	One 1.5 ml vial of Tixagevimab and one 1.5 ml vial of cilgavimab IM. Protective for 6 months	Hospital or non-hospital	Pre-exposure prophylaxis in high risk patients¹	Potential for allergic reaction, HA, fatigue cough, cardiovascular events including myocardial infarction and heart failure.	EUA issued on 12/2/21 for use in those 12 years and older and at least 40 kg.
Monoclonal antibody	Sotrovimab by GSK	One 500 mg vial given IV once.	non-hospital	Non-hypoxic COVID-19 infection in high risk patients¹	Potential for allergic reaction	EUA issued on 12/16/21 for use in those 12 years and older and at least 40 kg

¹ Conditions associated with high risk to severe disease and or death are not limited to, but may include older age (for example ≥65 years of age) • Obesity or being overweight (for example, adults with BMI >25 kg/m2 , or if 12 to 17 years of age, have BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm) • pregnancy • chronic kidney disease • diabetes • Immunosuppressive disease or immunosuppressive treatment • Cardiovascular disease (including congenital heart disease) or hypertension • chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension) • sickle cell disease • neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies) • having a medical-related technological dependence (for example, tracheostomy

² For a complete list of medication interaction see “Fact Sheet for Healthcare Providers Emergency use authorization for Paxlovid^TM” https://www.fda.gov/media/155050/download.

Get to know Marc Mazade, M.D.

I went into infectious diseases because my infectious diseases professors were among the most passionate doctors and teachers who invested in medical students and residents.

When I got into infectious diseases fellowship and received that one-on-one training on a daily basis, my career started blossoming. Everything started coming together. My professors challenged me to keep reading, thinking, and researching, while instilling in me the quiet patience that's required to keep digging via a friendly conversation with kids and their families to uncover a potential diagnosis that might explain an illness.

Kids are fun to treat, because they aren't weighed down by a life of poor health decisions that compromise their chances of getting better. It makes me feel great to see kids get well and back to living the lives they love - playing with toys, going to school, drawing and painting, or participating in dance, sports, band, choir, youth group, or just spending enriching time with their families and friends.

I like mentoring upper level medical students and helping them develop their knowledge of infections that are common in children. They often remember things that I've forgotten. When I'm not at Cook Children's, I love working on my tennis serve and backhand, fishing the abundant lakes, streams and bays of the region, and turning the pages of a well written medical mystery novel.