Hello everyone, I am Dr. Li.
At the beginning of this month, the "Guidelines for Home Treatment of COVID-19 Infections" came out, and all kinds of antipyretics were sold out in an instant. Up to now, ibuprofen and acetaminophen are still unavailable. Later I heard that Pfizer ’s special drug Paxlovid (nematvir/ritonavir tablets) was released. It was advertised as a special drug and could be purchased online. However, the price was very high, 2,980 yuan/box. There was an uproar in the public opinion, but the drug was soon removed from the online sales platform.
Everyone began to ask, Is there really a specific medicine for the new coronavirus ? Is this imported drug with such a high price really effective?
Everyone is curious, don’t worry, you will understand after reading this article.
. The specific drugs mentioned in the guide (versions 1-8)
The new coronavirus is a virus . If we want to talk about specific drugs, they must be antiviral drugs. Just like treating hepatitis C , we have specific drugs, so hepatitis C can be cured. We also have a specific drug to treat syphilis , which is penicillin. We are always looking for effective medicines.
But the reality is that effective drugs are often absent.
In early 2020, when COVID-19 struck, the National Health Commission launched the "Diagnosis and Treatment Plan for Pneumonia Infected by Novel Coronavirus" (Trial Version 1). It bluntly stated that this is a viral infectious disease. According to everyone's understanding, it seems that antiviral drugs It is a specific drug. Unfortunately, there were no effective antiviral drugs at the time, so the guidelines at the time said: There is currently no effective antiviral drug. Alpha-interferon aerosol inhalation and lopinavir/ ritonavir can be tried to treat . Of course, treatment also includes many other important ones, including hormones, traditional Chinese medicine, mechanical ventilation, ECMO, etc., but I will not talk about them here. I will only talk about anti-viral ones here.
Interferon is a broad-spectrum antiviral drug. Before this, it was commonly used clinically to treat diseases such as hepatitis B (hepatitis B is also a viral disease). Lopinavir/ritonavir is also an antiviral drug and has been used to treat AIDS (AIDS is also a viral disease), this medicine has a trade name called Kaletra. From this name, everyone will know that it specializes in treating AIDS. Trade names are not chosen casually. They all have connotations and will make people understand, but they cannot be too explicit, otherwise it will be illegal.
Anyway, as everyone knows, the antiviral drugs used to treat the new coronavirus at that time were all drugs previously used to treat other viral diseases. These drugs were available early on, and they were not hurriedly produced to treat new coronavirus .
Facts have proved that interferon and lopinavir/ritonavir are not very effective. We also used a lot of these drugs in Wuhan at that time, but we did not find any significant help to patients. At that time, everyone was groping and trying any potentially effective medicine, but the results were disappointing.
Later, in order to better control the epidemic, the National Health Commission revised the above guidelines eight times.
The "Diagnosis and Treatment Plan for Pneumonia Infected by Novel Coronavirus" (Trial Second Edition) was soon launched. When it comes to antiviral treatment, it still says: There is currently no effective antiviral drug. You can try alpha interferon aerosol inhalation, lopinavir/ritonavir 2 pills each time, twice a day. The third version of the pilot guide for
has also come out. The description of antiviral drugs has inherited the previous statement without changing a word. The fourth edition of the
guide has also come out, and it remains unchanged.
The fifth edition of the guide came out soon. In just half a month, five editions of the guide were updated successively, which is unprecedented. There are some slight changes in the statement about antiviral drugs, which is not called a change, but an increase. The guideline first describes what it said before: There is currently no confirmed effective antiviral treatment, but interferon and lopinavir/ritonavir can be tried. In addition, ribavirin may be added. Pay attention to lopinavir/ritonavir-related adverse reactions such as diarrhea, nausea, vomiting, and liver function damage.
The fifth edition has two changes. One is the addition of ribavirin , an ancient antiviral drug. Because some people said at the time that this drug might be effective, it was added to the guide. Ribavirin is originally a broad-spectrum antiviral drug. It is a very old drug. It was previously used to treat hepatitis C or other viral diseases.
The second change is to remind us to pay attention to the side effects of lopinavir/ritonavir (Kaletra). I am still very impressed by this, because after using this drug for a period of time, many patients have found problems with liver function , which is probably related to this drug, so the guide deliberately pointed it out.
In general, the fifth edition of the guidelines mentions three antiviral drugs: alpha interferon, lopinavir/ritonavir, and ribavirin. Although there are three axes, these three axes cannot cut, and the effect is not very good. But I have to make recommendations, otherwise there will be no medicine available. This is my personal understanding.
The sixth edition of the guideline came out soon. Regarding antiviral drugs, this edition of the guideline has undergone major changes. I posted the original text:
First of all, the sixth edition of the guideline removed the sentence "antiviral drugs that currently have no definite evidence of effectiveness." This sentence was used in the fifth edition of the guideline, and was removed in the sixth edition. It directly states that five antiviral drugs, alpha interferon, lopinavir/ritonavir, ribavirin, chloroquine phosphate, and arbidol, can be tried.
Among them, alpha interferon and lopinavir/ritonavir have always been recommended for trial. They are considered veteran drugs. It is difficult to say whether they are effective or not, but they have always been recommended for trial.
Ribavirin is again recommended for trial, but with added restrictions, that is: it is recommended to be used in combination with interferon or lopinavir/ritonavir. This means that ribavirin cannot be used alone because it is not powerful enough and must be used in combination with other drugs.
Two new drugs were added, one chloroquine phosphate and one Arbidol . We had all used them at the time. Anyway, we used whatever the guidelines recommended, and everyone could only do this. The disease came too fast, and the severe patients were too fierce. Everyone did not have good experience, so we could only work together.
Chloroquine phosphate was originally a drug to treat malaria, but later studies found that it has a certain inhibitory effect on the new coronavirus, so it was added to the guidelines. Arbidol is a genuine antiviral drug, but it is also a very old drug. It was developed by the Soviets and was first launched in Russia in 1993 to treat influenza. However, later research by the team of academician Li Lanjuan of and concluded that it has an inhibitory effect on the new coronavirus, so the guideline also included it and recommended it to clinicians.
Now, there are 5 antiviral drugs. The expert group is worried that clinicians will use them on patients regardless of care, so they once again remind everyone to pay attention to the side effects of drugs. It is not recommended to use 3 or more antiviral drugs at the same time, and everyone should observe while using them to see if the effect is good. If it is not good, take it out, and if it is good, continue to use it. At the same time, you can accumulate experience and use it to revise new guidelines.
This is the seventh edition of the guide. The introduction of antiviral drugs in the seventh edition guide is exactly the same as in the sixth edition, without any changes. It means that there was no new understanding at that time, so everyone should just follow the old method. You can try all 5 antiviral drugs.
In August 2020, the eighth edition of the guidelines came out. At that time, our domestic epidemic was well controlled. The eighth edition of the guidelines made major changes in the introduction of antiviral drugs.
First of all, the eighth edition of the guidelines emphasizes: Although no definite and effective antiviral drugs have been found, some clinical observational studies have shown that certain drugs have a certain therapeutic effect, and it is unanimously agreed that drugs with potential antiviral effects should be used early in the course of . It is recommended that they be used mainly in patients with who have high-risk factors for severe disease and who are prone to severe disease..
This sentence means that these potentially effective antiviral drugs should be focused on those patients whose condition may be relatively severe (those with high risk factors for severe disease or prone to severe disease), rather than using a wide net. Those who do not have high risk factors for severe disease do not necessarily need to use it, or do not need to use it at all.
Additionally, lopinavir/ritonavir and ribavirin are not recommended for use alone. This sentence also pulled down lopinavir/ritonavir. Research shows that its fate is the same as ribavirin. It has no effect when used alone, so it is not recommended to use them alone.
Also, does not recommend the use of hydroxychloroquine . Hydroxychloroquine is also an anti-malarial drug, somewhat similar to chloroquine phosphate, but different. At first, some people said that since chloroquine phosphate is somewhat effective, would hydroxychloroquine also be effective? Later, it was proved that hydroxychloroquine is not very effective, so the guide deliberately mentioned this drug and did not recommend the use of hydroxychloroquine.
The drugs that you can continue to try include: alpha-interferon, ribavirin (combined with interferon or lopinavir/ritonavir), chloroquine phosphate, and arbidol. It is not recommended to use 3 or more antiviral drugs at the same time.
In April 2021, the expert group revised the eighth edition of the guidelines (diagnosis and treatment plan) and released a "Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Eighth Edition Revised Edition)". The changes in the revised version are mainly in other aspects. There are no changes in antiviral drugs. It can be considered that there is no difference from the previous eighth edition, and they are still the same drugs.
. Two blockbuster news
There are two blockbuster news in the second half of 2021.
The first big news is: On December 22, 2021, the US FDA emergency approved Pfizer's oral COVID-19 drug Paxlovid for people over 12 years old and weighing at least 40 kilograms, making it the first approved oral COVID-19 drug in the United States, a protease inhibitor specifically used to combat COVID-19. This is a landmark event. Studies show that Paxlovid reduces the risk of hospital death by 89%.
Immediately afterwards, on February 11, 2022, the my country Food and Drug Administration also approved the marketing of Paxlovid in my country for the treatment of adult patients with mild to moderate COVID-19 who have high risk factors for progression to severe disease, such as patients with advanced age, chronic kidney disease, diabetes, cardiovascular disease, chronic obstructive pulmonary disease and other high risk factors for severe disease.
The second big news is: On December 8, 2021, my country's independently developed neutralizing antibody combination treatment drug ambavirumab/romisevirumab injection was approved for the treatment of adult and adolescent patients with new coronavirus infection who have mild and common types and are associated with high risk factors for progression to severe disease. Studies have shown that the drug can reduce the composite of hospitalization and death by 80% in outpatients at high risk of disease progression. No subjects in the treatment group died during the 28-day treatment period, while 9 patients in the placebo group died.
The above two blockbuster news involve two drugs to treat COVID-19, one is from the United States and the other is from China. The approval of these two drugs has rewritten the guidelines for the diagnosis and treatment of COVID-19.
. The Ninth Edition of the New Coronavirus Pneumonia Diagnosis and Treatment Plan
Above we have introduced the 1-8 editions of the guidelines. By March of this year (2022), due to the constant changes in the virus, various clinical research results have also come out (including the two blockbuster drugs mentioned above), and a lot of information has to be updated. Therefore, based on the revised eighth edition, the National Health Commission released the ninth edition of the guideline, which is the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Ninth Edition)". The new edition of the guideline proposes that the Omicron strain has replaced the Delta strain as the main epidemic strain. Existing evidence shows that Omicron has stronger transmissibility than Delta, but its pathogenicity has weakened .
Let’s focus on the introduction of antiviral drugs.
The ninth edition of the guidelines further standardizes antiviral treatment.The new guidelines have deleted several previously recommended drugs, including alpha-interferon, ribavirin, lopinavir/ritonavir, chloroquine phosphate, and arbidol, all of which have been deleted. Because there is not enough clinical evidence to show that these drugs are effective. In other words, although we have been using them for so long, we may have done nothing.
The new guideline no longer says that there are no antiviral drugs with proven efficacy, but directly recommends two new drugs. Yes, the two blockbuster drugs mentioned above! There are two specific anti-new coronavirus drugs approved by the State Food and Drug Administration at the end of 2021, and they have been written into the guidelines, namely:
Nematvir tablets/ritonavir tablets combination packaging (PF-07321332/ritonavir tablets) (Paxlovid) and domestic monoclonal antibodies (ambavirimab/romisevirumab injection).
This change is huge.
This shows that the guidelines are confident in these two drugs, because their efficacy is supported by relatively high-quality clinical studies. The more eye-catching one is Paxlovid from Pfizer of the United States. First of all, it is a drug produced by Pfizer of the United States. It is undeniable that Pfizer is an excellent pharmaceutical company, so Paxlovid represents advancement in the eyes of many people. Secondly, this medicine is taken orally, which is more convenient than the domestic monoclonal antibody injection type. So much so that in the eyes of many people, Paxlovid is a miracle drug!
Is Paxloivd really a miracle drug?
Of course not! At least, not entirely!
. Is Paxlovid a specific drug?
The answer is very clear, it is not a magic medicine.
Strictly speaking, what is a specific medicine? Only when the effect is particularly good can it be called a special medicine. For example, Bingtongsha can treat hepatitis C. It can directly kill the virus and cure hepatitis C. This is called a special medicine. Another example is syphilis. To treat syphilis, penicillin can directly kill Treponema pallidum and achieve recovery. It is called a special medicine.
No matter whether it is Pfizer's Paxlovid or domestic monoclonal antibodies, they cannot achieve similar effects as protonsa and penicillin. They have certain curative effects, but they are really not effective drugs.
Let’s look at Paxlovid, a study that included 2246 unvaccinated patients with at least one high-risk factor. The drug was administered within 3 days of symptom onset. The results showed that it reduced hospitalization or death events by 88% during the 28-day observation period (0.77% vs. 6.31%). This 89% is a relative effect. This number is real, but it is different from the drug effect that the general public understands.
The specific situation is that among the 1,039 high-risk patients who received Paxlovid treatment, 8 (0.77%) were hospitalized or died, while among the 1,046 control group patients, 66 (6.31%) needed to be hospitalized and died. According to this set of data (0.77% vs 6.31%), a conclusion of 88% relative effectiveness of the drug can be drawn. But the actual difference in the proportion of severe cases between the two groups was 5.54%. In other words, among these high-risk patients, even if they take a placebo, about 94% of them will not need to be hospitalized or die. Timely use of Paxlovid can increase this proportion to about 99%.
For low-risk patients, the effect of Paxlovid is very limited. In a study involving more than 100,000 patients, 4% took Paxlovid. Among infected people older than 65 years old, the drug reduced the risk of hospitalization by about 75%, but there was no obvious benefit in the 40-64 age group. In other words, if treatment prevents one hospitalization and death for every 300 low-income patients, that means there are at least 299 people who will suffer adverse effects from the drug without seeing any benefit at all. A drug like
can only be said to be one of the most effective new coronavirus treatment drugs at present, but it cannot be said to be a specific drug.
Because of this, the limited indications for Paxlovid in the ninth edition of the guidelines are: The applicable population is adults and adolescents (12-17 years old, body weight ≥ 40kg) with mild and common forms within 5 days of onset and with high risk factors for progression to severe disease. It also says to read the instructions before use and not to use it in combination with pethidine, ranolazine and other drugs (many drugs are omitted here).
Please see clearly:
(1) It can only be used within 5 days of the onset of illness. If it is used for more than 5 days, the effect will not be good. If it is used again, it will only have side effects and will not have any curative effect.
(2) Only used for light and ordinary types, but not effective for heavy and critical types.
(3) It should only be used by patients with high-risk factors for progression to severe disease. Simply put, it should only be used by high-risk patients and should not be used by low-risk patients because it is not helpful to low-risk patients.
The above are the factors for high-risk patients. To put it bluntly, even if you have mild or ordinary COVID-19, if you do not have the above-mentioned high-risk factors, it is not recommended that you use Paxlovid. In addition, if you are not infected with the new coronavirus, this medicine cannot prevent infection.
In the same way, domestically produced monoclonal antibodies are not considered specific drugs. It can only be said that these two drugs are currently COVID-19 treatment drugs that have a certain efficacy with more evidence.
In addition, drugs like Paxlovid are not without side effects. The side effects currently shown may include changes in taste, gastrointestinal reactions, increased blood pressure, muscle pain, etc.
Young people (under 60 years old) and low-risk people, using it may not necessarily shorten the course of the disease, reduce the risk, or alleviate the symptoms. What is it used for? This medicine cannot prevent disease, and it will be useless if used too early. What is it used for?
This medicine should be used by patients under the guidance of professional doctors. It is difficult for ordinary people to identify whether they are at high risk. How many people read the guidelines? Everyone only knows that there is such a "special medicine" and they don't care about who is suitable to take it.
I would like to ask, is it suitable to put such a drug on an online sales platform so that everyone can buy it with a prescription issued by an online doctor? And the price is 2980 yuan/box. Does this make people panic, and they always feel that if they have no money, they have to wait for death, and only rich people can buy this medicine?
Therefore, it is correct for the online platform to remove this drug from the shelves. This drug is qualitatively different from acetaminophen and ibuprofen.
5. There is more than one "special medicine"
As we said, these drugs are not special medicines, so we put them in double quotes.
The domestic ambavirumab/romisevirimab injection is considered by everyone to be a "specific drug". This drug is a combination of two neutralizing antibodies. They work together to form a combined punch. Research shows that the effect is not much different from Paxlovid. Both have their own advantages and disadvantages. The disadvantage of this monoclonal antibody is that the injection is more troublesome to use, but fortunately, it only requires one dose, which is more trouble-free. The indications for the use of this monoclonal antibody are also: patients with mild and common types and high risk factors for progression to severe disease. They are all used for high-risk patients, and ordinary low-risk people do not need to join in the fun.
There is another drug called Azivudine , which is also made in China.
Azivudine is an innovative drug against HIV virus developed by Zhengzhou University Professor Chang Junbiao as the inventor. In 2013, it was approved to enter clinical trials. In 2021, Azivudine was officially approved for marketing as an anti-AIDS drug and was included in the 2021 version of the "China AIDS Diagnosis and Treatment Guidelines". Azivudin began to be used in COVID-19 treatment research in 2020. In April 2022, Azivudin completed phase III clinical trials at home and abroad. In July, Azivudin received emergency conditional approval from the State Food and Drug Administration, becoming the only domestically produced oral COVID-19 drug approved for emergency use. (The domestically produced monoclonal antibody above is an injection, and this one is an oral drug)
Azivudine’s Phase III clinical trial results show that it can shorten the time for symptom improvement in moderate COVID-19 patients and increase the proportion of patients with clinical symptom improvement. In August 2022, the Health Commission and the Bureau of Traditional Chinese Medicine issued a document to include Azivudine Tablets in the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Ninth Edition)", and stated its indications: for the treatment of adult patients with common new coronavirus pneumonia .
But in fact, the ninth edition of the guidelines was released in March, so the ninth edition of the guidelines we see now does not contain Azivudine, only Paxlovid and monoclonal antibodies. However, the National Health Commission has issued an announcement that Azivudine has been included in the guidelines. So when the revised ninth or tenth edition of the guidelines is released in the future, Azivudine will definitely be included. This is my understanding.
In this way, there are three so-called new coronavirus specific drugs for us to choose from, namely: Paxlovid, ambavirumab/romisevirumab injection, and Azivudine tablets. The first one is from Pfizer of the United States, and the latter two are independently developed in China. This kind of scene is rare. Historically, the drugs recommended in our various guides have mostly been imported drugs. This time we have actually done the work and achieved results, so we can write it into the guide.
But I would like to remind everyone that although Azivudine tablets are also so-called specific drugs, their indications are common forms of COVID-19. It does not include mild cases, let alone asymptomatic infections. Please do not use them without permission. Besides, medicines all have side effects. You should weigh the pros and cons before taking them, not just take them when you want. Last month, online sales of Azivudine were stopped after just one day. How could this kind of drug be easily sold online? It’s not like you don’t know how fake the prescriptions for drugs sold online are.
Don’t get excited when you see the words “special medicine”!
Special medicines and special medicines. We are always looking for special medicines, but they are often absent. When I say that the above-mentioned drugs are not effective drugs, I do not deny their clinical value, but there is still a distance between them and effective drugs. Moreover, they are not without side effects and cannot be bought and eaten at will.
I wish everyone good health.
