On July 30, 2022, White House Presidential Physician Kevin O’Connor issued a written letter stating that US President Biden “returned” to the new crown.
White House Presidential Physician Kevin O’Connor issues written letter
Previously, on July 21, the White House issued a statement saying that Biden tested positive for the new crown virus. At that time, Biden had completed the full vaccination and received 2 booster shots. The White House said Biden would take Pfizer’s oral antiviral drug Paxlovid for treatment.
Then on July 27, the White House announced that Biden’s new crown virus test result turned negative.
According to the latest letter, Biden tested positive on Saturday morning after testing negative for the new coronavirus four times in a row on Tuesday, Wednesday, Thursday and Friday, but not again Symptoms appear. The White House presidential doctor said there is currently no reason for a new round of treatment for Biden, but the strict isolation procedure will be restarted.
Paxlovid Fuyang: Not a Case
Biden’s experience is not an isolated case. White House Presidential Physician Kevin O’Connor also mentioned in the latest written letter that a small number of new crown patients treated with Paxlovid may have the possibility of recovery.
Previously, Anthony Fauci, Chief Medical Adviser to the President of the United States, also experienced Paxlovid rebound. He then underwent a second course of Paxlovid treatment as recommended by his doctor.
He Dayi, a Chinese scientist and inventor of AIDS “cocktail therapy”, also experienced “Paxlovid Fuyang”. He received a course of Paxlovid treatment after the infection, and on the seventh day after the course, he tested positive again for Covid-19.
“If you test positive, you have to assume that you are contagious to others.” He said in an interview with JAMA.
After experiencing “Paxlovid Fu Yang” personally, He Dayi published a preprinted paper as the corresponding author, recording the “Paxlovid Fu Yang” in 10 non-immunocompromised patients aged 31 to 71 years old. Yang” situation.
Paper screenshot
The paper shows that the symptoms of the vast majority of patients improved rapidly and the nucleic acid turned negative after receiving Paxlovid treatment; some Fuyang patients reported symptoms of fatigue and headache; All recovered with additional antiviral treatment; viral gene sequencing of 3 patients showed that the fuyang was not caused by infection with other strains; 2 patients transmitted the virus to other family members during the revival.
Additionally, in a Mayo Clinic study published this month in Clinical Infectious Diseases, 4 (0.8%) of 483 high-risk patients treated with Paxlovid experienced a rebound in symptoms ( rebound), but basically all were mild, and their antigens or nucleic acids turned negative after 3 to 5 days of no further treatment.
Paper screenshot
However, the limitation of this study is that it was a retrospective study, not a placebo-controlled double-blind trial, so some experts believe that the 0.8% re-positive rate is likely an underestimate . In Pfizer’s Phase III clinical trial, about 1% to 2% of the subjects also had a relapse.
In addition to Paxlovid, another oral antiviral drug for Covid-19, Molnupiravir, has also reported recovery after use.
According to a study by Case Western Reserve University School of Medicine, both Paxlovid and Molnupiravir have a certain probability of re-yang after treatment, and symptomatic re-yang after 7 days of treatment for both drugs The rates were 2.31% and 3.75%, respectively, and the rates of inpatient treatment were 0.44% and 0.84%, respectively.
After matching risk factors, there was no significant difference between the two drugs in the rebound of the new crown, and the prevalence of underlying diseases in patients with Fuyang was significantly higher than that in patients without Fuyang.
Image source: Reference 3
Principle: or non-resistance
Why did the “Paxlovid Fu Yang” happen?
A recent study published in Clinical Infectious Diseases performed drug resistance testing and neutralizing antibody testing on a virus isolated from a “Paxlovid-positive” patient, suggesting that, The reason for “Paxlovid Fuyang” may not be due to the fact that the new coronavirus has developed resistance to Paxlovid, nor is it caused by the lack of neutralizing antibodies.
Researchers believe that Paxlovid Fuyang is most likely due to insufficient exposure or duration of exposure to the drug.
Image source: Reference 4
The main ingredient of Paxlovid, PF-07321332, is a 3CL protease inhibitor of the novel coronavirus. For single-stranded RNA viruses such as the new coronavirus, its replication must be completed in the host cell. During replication, RNA first encodes 2 large multimeric precursor proteins and 4 structural proteins. Polyproteins require proteolytic hydrolysis to produce short, nonstructural proteins that facilitate viral replication.
Based on the observations in the above studies, “Paxlovid Fuyang” is likely because, during a 5-day course of treatment, the virus replication in the patient’s body was inhibited. , but there is still live virus. After the course of treatment is over, the live virus may replicate again, resulting in a return to yang.
However, since the human immune system has been mobilized and the level of neutralizing antibodies has increased, Fuyang does not mean an increased risk of severe disease, and most patients with Fuyang do not need additional treatment. Can be turned negative again.
In addition, there are some hypotheses that “Paxlovid revival” may be because the vaccine coverage rate is already high, and the premature use of antiviral drugs reduces the exposure of antigens in the immune system, affecting the Humoral/cellular immune response; another possibility is that Omicron (and its offshoots) may take longer to peak or be cleared than previous SARS-CoV-2 variants.
However, further research is needed to confirm these hypotheses.
Is it necessary to extend the duration of medication?
Currently, under US FDA approval, Paxlovid is available for use in adult and pediatric patients (ages 12 and older weighing at least 40 kg or 88 lbs). Treatment should be started as soon as possible within 5 days of symptom onset if you are eligible for EUA treatment and if:
-Tested positive for SARS-CoV-2 infection
-mild to moderate symptoms
-Have one or more risk factors for progression to severe disease
-non-serious or hospitalized conditions at the start of treatment
-No severe liver and kidney damage.
Patients treated within three days of symptom onset had an 89% reduction in hospitalization or mortality compared with placebo, according to Paxlovid’s Phase III trial;Patients who received Paxlovid within 5 days of symptom onset had an 88% lower risk of hospitalization or death compared to those who received placebo.
After the approval of the EUA, other research institutions have published the effectiveness data of Paxlovid.
Mass General Brigham’s preprint study published in medrxiv shows that the overall risk of hospitalization is already low among outpatients diagnosed with COVID-19 (
Paper screenshot
Israeli study published this month in Clinical Infectious Diseases showed that among 4,737 patients treated with Paxlovid (about 75% were vaccinated), there was a 46% reduction in the risk of severe illness and a reduced risk of death 80%, and Paxlovid was more effective in elderly patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease.
Researchers believe that Paxlovid was very effective in reducing the risk of severe illness and death in the real world during the Omicron era.
Paper screenshot
So, what impact will Paxlovid Fuyang bring?
On May 24, the US CDC responded to “Paxlovid Fuyang”.
CDC said that the recovery of new crowns generally occurs 2 to 8 days after turning negative, and the recovery may be part of the natural history of new crown infections and has nothing to do with Paxlovid treatment and vaccination. These re-positive cases improved without additional treatment, including symptoms and nucleic acid test results (median 3 days).
CDC mentions that whether patients receive antiviral drugs or not, there may be a risk of transmission during the recovery period and still need to be managed according to CDC isolation guidelines. However, judging from the reported cases so far, there is no case of Fuyang patients with severe symptoms.
Previously, Pfizer, the research and development drug company of Paxlovid, said that in view of the report of “Paxlovid Fuyang”, it may consider recommending to extend the treatment course of Paxlovid, or recommend that patients with Fuyang take Paxlovid again for treatment . However, this view was subsequently questioned by some scholars, who believed that prolonged treatment was unnecessary and would significantly increase the cost of treatment.
The CDC also believes that there is currently no evidence that “Paxlovid Fuyang” needs additional treatment. (Planner: z_popeye | Producer: gyouza)
Acknowledgments: I would like to thank Zhou Yebin, a medical research and development practitioner, Master of Neuroscience, Hokkaido University, and Weibo Popular Science University V Zhuang Shili for their contributions to this article
Image source: YouTube video screenshot
References:
[1]Rapid Relapse of Symptomatic Omicron SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir. Research Square. doi.org/10.21203/rs.3.rs-1588371/v3
[2]DOI: 10.1093/cid/ciac481
[4]https:https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac496/6611663
[6]DOI: 10.1093/cid/ciac443
[7]https:https://emergency.cdc.gov/han/2022/han00467.asp