You should seriously consider prescribing an antiviral agent either oral nirmatrelvir-ritonavir (Paxlovid) (within 5 days of onset of symptoms) or IV remdesivir (within 7 days of onset of symptoms) in all your ambulatory patients with mild/moderate Covid-19 at high risk of progression (ie, ≥1 risk factors) to severe disease (Figure). ^1-3 Both of these drugs reduce hospitalization and mortality from Covid-19 by over 85%!¹ Oral molnupiravir may be prescribed as a second-line agent (within 5 days of onset of symptoms), if neither Paxlovid or remdesivir is an option and the patient is not pregnant. There is no indication for the use of  dexamethasone or systemic steroids in the treatment of Covid-19 in ambulatory settings. As with all drugs, you should be familiar with adverse-effects and contraindications of these anti-viral agents before prescribing them. 

Couple of questions to ask when managing a patient with newly diagnosed Covid-19 in ambulatory setting:

1. Does your patient truly have mild/moderate disease (eg, Sp02 on room air ≥94% on room air and not tachypneic) or severe disease (eg, Sp02 on room air <94%)?⁴ If severe disease is likely, you should refer your patient to a hospital for evaluation and treatment as soon as possible. If your patient is not symptomatic from Covid-19, no antiviral treatment is indicated. 
2. Once you decide your patient has mild/moderate disease and doesn’t need to go to hospital, ask whether your patient has any risk factor associated with progression to severe Covid-19.² Recall that there are numerous risk factors, including age over 50 and many physical disabilities, smoking (current or former) and mental health disorders, such as depression, ADHD, autism and depression that may be present even in the younger population.²
   • In the absence of any risk factor for progression, no antiviral therapy is indicated.

In the presence of 1 or more risk factors for progression or contraindications, you should consider initiation of Paxlovid x 5 days, if within 5 days of onset of Covid-19 symptoms or IV remdesivir x 3 days, if within 7 days of onset of Covid-19 symptoms.  

• Remember that although Paxlovid may potentially interact with numerous drugs, fewer such drugs are absolutely contraindicated. Convenient online resources are available to help you decide if your patient can still receive Paxlovid safely.
• Also don’t forget that remdesivir can now be given without dosage adjustment in renal insufficiency, including those on dialysis. 

If for some reason neither Paxlovid nor remdesivir is an option, oral molnupiravir can be considered with some caveats, including recommendations against its use during pregnancy and use of effective contraception during and following treatment in people who engage in sexual activity that may result in conception. 

Irrespective of treatment, it is prudent to monitor for any deterioration of sp02 at home when managing patients with mild/moderate Covid-19.  

Bonus pearl: Did you know that despite its high efficacy (89% reduction in hospitalization and death) against Covid-19,^1,5 Paxlovid is severely underutilized in the outpatient setting with fewer than 25% of eligible patients with Covid-19 receiving it?⁶

Figure: Covid-19 management in ambulatory adult patients

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References

1. Rubin R. Paxlovid Is Effective but Underused—Here’s What the Latest Research Says About Rebound and More | Infectious Diseases | JAMA | JAMA Network Published online January 31, 2024. doi:10.1001/jama.2023.28254
2. Interim Clinical Considerations for COVID-19 Treatment in Outpatients | CDC. Accessed Feb 1, 2024
3. Molnupiravir | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024.
4. Clinical Spectrum | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024
5. Appaneal HJ, LaPlante KL, Lopes VV, et al. Nirmatrelvir/ritonavir utilization for the treatment of non-hospitalized adults with Covid-10 in the National Veterans Affairs (VA) Healthcare System. Infectious Diseases and Therapy 204;13:155-172. Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System | Infectious Diseases and Therapy (springer.com)
6. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022; 386:397-408. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 – PubMed (nih.gov)

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!