One of the ongoing challenges with COVID-19 has not only been prevention, but also therapeutics. How do we treat people who are hospitalized with mild symptoms? Nonhospitalized patients? More and more the use of medical countermeasures becomes increasingly a topic of concern and discussion as we look to the future of COVID and that we will likely living with it longer than we’d like.

Often discussions around therapeutics are centered around hospitalized patients, but how do we approach treatments for nonhospitalized patients? A new article published in JAMA seeks to address how we approach treatments for these patients who are not hospitalized, but experiencing COVID-19. For mild and moderate COVID-9 symptoms, how should we treat them? Even more relevant—how does this change with Omicron, a variant that is more transmissible but increasingly considered less severe. As the authors noted, “Antivirals target different stages of the SARS-CoV-2 life cycle. Anti–SARS-CoV-2 monoclonal antibodies bind to the viral spike protein, preventing attachment and entry into cells. Nirmatrelvir-ritonavir inhibits the SARS-CoV-2 main protease, which cleaves viral polyproteins into nonstructural proteins essential for replication. Molnupiravir and remdesivir target SARS-CoV-2 RNA replication: the former induces RNA mutagenesis leading to virus that is unable to replicate and the latter is a nucleotide prodrug that inhibits viral RNA polymerase. Because of mutations in the viral spike protein of the Omicron variant, most currently available anti–SARS-CoV-2 monoclonal antibodies have reduced activity. Nirmatrelvir-ritonavir, remdesivir, and molnupiravir, which target more conserved viral regions, are expected to remain active against Omicron.”

The authors reviewed Sotrovimab, Nirmatrelvir-ritonavi, Remdesivir, and Molnupiravir in nonhospitalized patients noting mechanisms of action, trials, and outcomes. Moreover, the researchers developed a table for each therapy and its advantages and disadvantages, which breaks down serious drug interactions and situations where one drug was preferred over the other. One very beneficial piece to this article and research, was a discussion on treatment for children and pregnant people, but also allocating treatments when there are supply chain issues.

The authors noted that “Patients at highest risk for severe disease should be prioritized. The NIH COVID-19 treatment guidelines have proposed a prioritization scheme for when there are logistical or supply constraints. When the number of patients in the highest risk tier exceeds medication supplies, other approaches such as lotteries may be needed. The distribution of medications should be actively monitored and adjusted to ensure equitable use (ie, vulnerable and disadvantaged individuals are not being excluded).”

Lastly, and most importantly, the authors emphasized future directions, which emphasized not only monitoring emergence of resistance in those receiving monotherapies, but also equitable distribution and the increasing importance of addressing such gaps. As the authors noted, there is a need to address therapeutics both at a micro and macro level, and where viral resistance may impact these efforts. In the face of Omicron and what future variants may throw at us, an evaluation of medical countermeasures for nonhospitalized patients is critical.