Similarly, the antiviral drug monopiravir (Lagevrio) received EUA in December 2021 for the treatment of mild to moderate COVID-19 in high-risk adults 18 years of age or older, when taken for 5 days starting within 5 days of symptom onset.
However, monupiravir was not as effective as Paxlovid in getting patients to reduce hospitalizations compared with placebo in clinical trials. Monupiravir is only authorized for use in patients for whom an FDA-authorized alternative COVID-19 treatment is not available or clinically inappropriate. Additionally, while Paxlovid is authorized for use in children 12 years of age, monopiravir is not authorized for use in children under 18 years of age because it may affect bone and cartilage growth. In addition, monopiravir can prevent SARS-CoV-2 replication, but the pathway is different from Paxlovid, and it is not recommended for pregnant women. Animal studies have shown that it may cause harm to the fetus.
Currently, the U.S. government has purchased 3100,000 courses of Monupiravir and 20 million courses of Paxlovid, which will be delivered this year.
The virus mutation is different from the early
The results of the EPIC-HR trial (evaluation of protease inhibitor treatment for COVID-19 in high-risk patients) published in April this year did not even mention rebound, and the EPIC-HR trial is the basis for the Paxlovid EUA. Omicron was also not mentioned because no vaccinated trial participants became infected with COVID-19 before Omicron became available.
This retrospective cohort study was conducted in Hong Kong, focusing on the nearly 1.1 million non-hospitalized patients diagnosed with SARS-CoV-2 infection in Hong Kong during the Austrian Micron BA.2.2 wave from February 26 to May 3, 2022. Among them, 5,257 were taking Monupiravir and 5,663 were taking Paxlovid.
Both antiviral drugs were associated with a lower risk of all-cause death compared with no antiviral drug - 39% lower risk with monopiravir and 75% lower risk with Paxlovid. Both were also associated with a lower risk of in-hospital disease progression compared with no antiviral drug — 36% for monopiravir and 53% for Paxlovid. Paxlovid reduced the risk of hospitalization by 31%, while patients taking monopiravir had the same risk of hospitalization as those not taking antiviral drugs.
In the Hong Kong study, the use of Paxlovid was associated with greater and more consistent protection than the use of monopiravir, with similar protection regardless of vaccination status and age. However, the authors noted that Paxlovid was significantly better than monopiravir in the study, which may be due in part to a higher proportion of patients over the age of 65 and a lower proportion of fully vaccinated patients receiving the latter drug.
Is it a drug problem, or is it a disease problem?
The U.S. CDC and the May 24 health advisory stated , "Transient recurrence of symptoms may be part of natural infection with SARS-CoV-2, Recurrent infection in some people is not related to Paxlovid treatment and regardless of vaccination status.
A study released by Dayi Ho on May 23 revealed that approximately 410 people (he was the second case described in the report) had returned positive after taking Paxlovid. When asked if he thought resurgence might be part of the natural process of SARS-CoV-2 infection, he responded that it was "definitely not a natural process."
Tatiana, breast cancer expert at Johns Hopkins University in the United States Prowell has heard from colleagues about cases of rebound in the natural history of the disease. She speculated that Omicron might be the source.
He Dayi refutes Pfizer ’s argument that rebounds are uncommon. He and his co-authors note that five of the 10 relapses described in their report occurred in two families, two in his family and three in another family, suggesting that the condition is not uncommon.
This is concerning, because it seems that people who experience a relapse can infect others, said He. In 10 cases, the viral load during the relapse was comparable to the level during the initial infection. Dayi He and his co-authors write that 1 symptomatic patient and 1 presymptomatic patient transmitted SARS-CoV-2 to family members during relapse .
Trying to figure out the cause of relapse
He Dayi may be one of the very few people who relapsed after taking Paxlovid, and then had his virus sequenced the first and second time. The results showed that both sequences of and Ho were identical to , ruling out several possible explanations for his recurrence. This could not be due to bad luck, which meant that he contracted a second SARS-CoV-2 infection just as he was recovering from his first. it can't be due to the virus becoming resistant to Paxlovid, if it were the virus sequence would not be the same as .
Scientists have proposed several other possible explanations for rebound after Paxlovid treatment. "The first question that came to my mind was the timing," Carlos said. "I thought we might be treating it too short." Wachter speculated: "If you start right away, maybe you'll suppress the virus, the immune system won't rev up as much as it normally would, and a 45-day course of treatment might not be long enough." But Wachter also admitted that all of these theories are moot.
To answer the outstanding questions about relapse, Carlos Said: "I'm not sure we need the classical definition of clinical trials , we need post-approval data, which is being collected for , but the findings may not be available for several months. Currently, there is no evidence that additional treatment with Paxlovid is required when relapse after a 5-day course of treatment is suspected .
Although there are a lot of questions about the phenomenon of relapse, Carlos said "our biggest challenge with this drug is that it is not used as frequently as it should be. Primary care physicians are concerned about drug interactions The people most likely to develop severe or even fatal infections with COVID-19 are also the people most likely to be taking multiple medications."
