Is Paxlovid a Game Changer? ... More Frequent COVID-19 Recurrences [Reading Science]

International Journal Nature Reports Recent Study Results
"Users Experience More Severe Rebound Effect Than Non-Users"

[Image source=Yonhap News]

[Asia Economy Reporter Kim Bong-su] Research results are emerging that show symptoms rebound are more severe in patients who took the so-called COVID-19 pandemic "game changer" treatment Paxlovid than in those who did not take it. It is an analysis that the so-called "Paxlovid rebound," widely known after being experienced by U.S. President Joe Biden recently, is being scientifically proven.

According to the international academic journal Nature on the 11th (local time), recent studies have reported that among COVID-19 infected patients, many cases initially seemed to improve but then showed increased viral loads and symptom relapse such as high fever, especially more severe and frequent in those who took the treatment drug Paxlovid.

Paxlovid is an oral antibody treatment developed by Pfizer in the United States, a combination of nirmatrelvir and ritonavir. It is known to block the protease enzyme (3CL protease), preventing the production of proteins necessary for viral replication, thereby inhibiting viral proliferation. Countries worldwide, including South Korea, have approved and widely used it since December last year. When administered within five days of symptom onset, it significantly reduces hospitalization and death rates, and was considered a "game changer" that could alter the course of humanity's war against the COVID-19 virus.

However, some people have experienced the so-called "Paxlovid rebound" phenomenon, raising global doubts about its effectiveness. Cases where patients seemed to recover but suddenly showed increased viral loads and symptom relapse have frequently appeared. Recently, President Biden's experience with this phenomenon sparked worldwide controversy.

The manufacturer Pfizer has practically denied this phenomenon. Pfizer published a paper presenting experimental results showing that Paxlovid reduces hospitalization and death rates in unvaccinated individuals. Regarding the Paxlovid rebound phenomenon, they countered that "symptom recurrence does occur, but it appeared in both the control and experimental groups in the study."

A research team at a hospital in Boston, Massachusetts, USA, undertook a study to verify Pfizer's claims. The team tracked 247 patients in the control group who were infected with COVID-19 and received a placebo in a large-scale Paxlovid clinical trial, reporting that about one-quarter experienced symptom relapse. However, among them, 12.5% showed only increased viral loads, and only about 1-2% showed both increased viral loads and symptom relapse such as high fever, indicating a significant "rebound" phenomenon. In other words, actual symptom relapse was rarer in patients who did not take Paxlovid than in those who did. A team member explained, "These results suggest that in patients not taking the drug, symptom recurrence such as high fever or sore throat due to COVID-19 virus rebound is rare," adding, "The most important implication is that the recovery process from COVID-19 does not always proceed smoothly."

There is also another study. A research team at Beth Israel Deaconess Hospital, also in Boston, tracked 11 Paxlovid-taking COVID-19 patients and 25 non-taking patients, confirming that over one-quarter of the Paxlovid group experienced symptom relapse, while only one out of 25 in the non-taking group did. Moreover, those with symptom relapse in the Paxlovid group maintained high viral loads for several days as if newly infected. The team stated, "Symptom relapse in non-taking patients appeared to be a temporary phenomenon," and "Symptom relapse in non-taking patients and Paxlovid rebound appear to be qualitatively different."

However, the cause of the Paxlovid rebound phenomenon remains unknown. Scientists believe it is unlikely due to drug resistance or weak immune responses in patients. Research is focusing on how viruses suppressed by Paxlovid return after the drug effect wears off, leading to high viral loads and strong immune responses causing symptoms like high fever to reappear. Mark C. Wiedner, a clinical epidemiology professor at Massachusetts General Hospital, noted, "It reminds us of phenomena seen when other diseases are treated too quickly," and pointed out, "For those experiencing Paxlovid rebound, it may be because the drug administration period was insufficient."