According to the World Health Organization (WHO), new coronavirus infections (COVID-19) have spread globally since December 2019, with more than 760 million cases and 6.9 million deaths so far, but the actual numbers are thought to be higher [1] and viral mutations have not stopped to date. In order to adapt and guide the standardized treatment of the disease, the WHO first published dynamic guidelines for COVID-19 drug therapy on September 4, 2020, providing direction to a wide range of clinicians, and on November 10, 2023, the WHO updated the guidelines for the 13th time. The latest version of the guideline makes revisions to the treatment recommendations for non-critically ill patients, while further clarifying the drug recommendations for COVID-19 treatment, with nematrevir/ritonavir tablets (Paxlovid) remaining the only drug strongly recommended for use in populations with a high and intermediate risk of hospitalization
1.Nematrevir/ritonavir remains the only highly recommended treatment for patients who are not critically ill and at high risk of hospitalization
WHO continues to strongly recommend the use of nematrevir/ritonavir in populations at high and moderate risk of hospitalization. The recommendation states that nematrevir/ritonavir is considered to be the best option for most eligible patients, given its therapeutic benefits, ease of administration, and fewer concerns about its potential harms.
2.For high-risk patients, nematrevir/ritonavir is a superior choice
The guideline development panel concluded that for non-critically ill patients at highest risk of hospitalization, nematrevir/ritonavir is more effective in preventing hospitalization of patients and has fewer adverse drug reactions than other alternatives, such as monupiravir, while being more convenient to administer and is the preferred choice for the treatment of high-risk patients.
3. Unchanged efficacy of nematrevir/ritonavir against different virus variants
Nematrevir/ritonavir prevents the cleavage of viral polyproteins by inhibiting 3CLpro, which in turn inhibits viral replication. Data from the study showed that the new mutant strain of the virus mutated mainly in the spiking protein rather than in 3CLpro; therefore, the efficacy of the drug was stable against the different mutant strains, and the pharmacokinetic indexes of efficacy were unchanged against the different strains of the virus.
4. VV116 treatment is not recommended for COVID-19 patients except in clinical trials
The new version of the guideline states that because there is still a high degree of uncertainty regarding the effect of VV116 on important outcomes such as admission, mortality, use of invasive mechanical ventilation, and time to symptom relief in patients with non-severe COVID-19, its use is limited to the context of clinical trials. Subgroup analyses based on age, disease severity, serologic or vaccine status could not be performed due to a lack of data, so it is assumed that the effects are similar in all subgroups and that this recommendation applies to patients with any disease severity and any symptom duration.