COVID-19 treatment, from panic to calmness
The beds are neatly arranged, and the critically ill patients in the ward are mainly elderly people, and the vital signs of the patients are constantly monitored by the equipment at the head of the bed. Doctors and nurses in protective clothing and fully armed are busy: recording patient information, answering work calls, preparing medicine, and organizing equipment; checking the patient’s vital signs, adjusting the parameters of the ventilator; helping the patient adapt to prone position breathing, turning over, checking and adjusting Rehydration speed, recording the patient’s body temperature…
This is the scene in the ICU (Intensive Care Unit) of the southern campus (designated hospital) of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine at the end of April this year. During the most stressful stage of the epidemic in Shanghai, tens of thousands of new crown infections were added every day. According to the pathogenicity of the new crown virus strain at that time, on the basis of the huge number of infected patients, some patients must develop into severe cases.
At that time, although there were many critically ill patients, the treatment was tense and orderly, and ensuring the treatment of those seriously infected with the new crown became a key to winning the “Great Shanghai Defense War”.
In the past three years since the outbreak of the new crown epidemic, medical staff around the world have gradually accumulated experience in the treatment. At the same time, with the successful development and application of new crown-specific drugs, the treatment of patients with new crown infection has changed from panic at the beginning to today.
What changes have taken place in the treatment of the new crown? Recently, Chinese doctors have summed up and published valuable clinical scientific research papers on the treatment of COVID-19, unveiling the mystery of COVID-19 treatment for ordinary people.
In early April 2022, before Renji South Hospital was converted into a designated hospital, medical staff transferred patients.
Specific drugs play a role in real life treatment
On April 22, 2022, the World Health Organization issued treatment recommendations for new coronary pneumonia. The guidelines pointed out that the only strong The recommended method is to use the combination of Naimatevir/ritonavir tablets PAXLOVID TM .
On July 14, 2022, the team of Director Ye Shuang of the Rheumatology Department of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Gao Yuan, Director of the Department of Critical Care Medicine joined forces to publish an international authoritative medical journal “The Lancet: Infectious Diseases” (impact factor 71 points) published a short paper online entitled “PAXLOVID TM for Immunosuppressive Hospitalized Patients with SARS-CoV-2 Infection”, adding important new evidence for the timing and target of clinical anti-coronavirus treatment.
The recommendations of the guidelines are based on the results of two RCT (randomized controlled trials), which included a total of 3078 people infected with the new crown. The data showed that after treatment with PAXLOVID TM , the risk of hospitalization of the subjects was reduced by 85%. In addition to a higher rate of severe disease prevention, PAXLOVID TM has the obvious advantages of less side effects and easier management than other similar drugs. Due to its clear efficacy, PAXLOVID TM has become the first choice of doctors and patients
since it was approved by the US Food and Drug Administration (FDA) . The above-mentioned paper published by Renji Hospital is the result of a real-world study during the Shanghai epidemic in 2022. It uses real-life patient treatment data to evaluate the efficacy of PAXLOVID TM in treating patients with new coronary pneumonia, and provides more practical treatment measures for patients with new coronary pneumonia. .
“PAXLOVID TM for Immunosuppressed Hospitalized Patients with SARS-CoV-2 Infection”
”The patients enrolled in the preliminary clinical trials had mild symptoms, with an average age of about 40 years old. They were mainly smoking, high BMI, hypertension, and diabetes patients. How effective is the virus clearance of PAXLOVID TM for patients with low levels of infection.” Gao Yuan said, in addition, although the guidelines recommend administering the drug within 5 days of onset or diagnosis, the number of people infected with new coronary pneumonia in Shanghai this time is large, and the infection of most patients has exceeded 5 days, “So we also wanted to know if administration 5 days after infection would affect the efficacy of PAXLOVID TM .”
In Ye Shuang’s view, the results of real-world research serve as a powerful supplement to clinical trials, making the evidence more sufficient and complete.
According to reports, the study included 114 patients with new crown infection who were admitted to Renjin South Hospital from April 7, 2022 to May 7, 2022. Elderly patients (average age 65.87 years old) were much more than PAXLOVID TM Phase II and Phase III patients. Among the patients enrolled in the clinical study, as many as 79% had comorbidities, and the types of comorbidities were complex, and the vaccination rate was low (26.5%). Among them, there were 35 immunocompromised patients (30.70%). The study concluded that PAXLOVID TM
should be administered early in infection in those patients who have not been vaccinated, especially immunocompromised elderly patients . ”As intensivists, we mostly deal with patients who have a clear tendency to become severe or who have already become severe. In fact, the best treatment is to prevent the patient’s condition from turning from mild to severe, rather than turning to severe for further treatment. Therefore, as soon as possible Identify high-risk patients, carry out symptomatic treatment in advance, and prevent the progression of the disease; especially in mass incidents, early identification and early treatment are particularly important.” Gao Yuan emphasized that most of the patients included in this study were high-risk elderly patients, who were extremely prone to infection. Initially from mild to severe. The results of the study showed that PAXLOVID TM
There is a clear linear correlation between the timing of use of PAXLOVID TM and the clearance time of the virus, suggesting that early medication (within 5 days) can slow down the progress of the patient’s disease course, that is, the earlier PAXLOVID TM is started , the faster the virus clearance will be. This provides new evidence for the treatment of patients with new coronary pneumonia in my country, and has important guiding significance for clinical diagnosis and treatment.
Ye Shuang believes that patients with rheumatic immune diseases often have abnormal immune function, making them susceptible to viruses and more likely to turn into critical illness. At the same time, severe COVID-19 often presents with excessive inflammation and immune response. Therefore, for patients with new coronary pneumonia with abnormal immune function, clearing the virus in the early stage of infection is the key to preventing their repeated infection and deterioration of their condition; for patients with inflammatory storms, timely and appropriate anti-inflammatory treatment is needed. “Our work It suggests that rheumatology and immunization can make a professional contribution to the fight against new coronary pneumonia.”
The importance of multidisciplinary treatment is highlighted
The premise of the above-mentioned research in Renji Hospital is that, firstly, Renji South Hospital was converted into a designated hospital; secondly, during the same period, PAXLOVID TM was quickly approved for mild and common patients with high risk factors for progression to severe disease within 5 days of onset. Adult COVID-19 patients.
In April this year, experts from designated hospitals of Renji Hospital had a collective consultation.
It is understood that PAXLOVID TM is the first oral drug approved for marketing in China. As early as February 11, 2022, the State Food and Drug Administration conducted emergency review and approval in accordance with the relevant provisions of the “Drug Administration Law” and in accordance with the special approval procedures for drugs. , conditionally approved the import registration of Pfizer’s new coronavirus treatment drug Naimatevir Tablets/Ritonavir Tablets Combination Packaging for the treatment of mild to moderate novel coronavirus pneumonia (COVID-19) in adults with high risk factors for progression to severe disease. 19) Patients, such as patients with severe high-risk factors such as advanced age, chronic kidney disease, diabetes, cardiovascular disease, and chronic lung disease.
After the outbreak of the epidemic in Shanghai in March this year, Renji Hospital received a notice from its superiors on April 3 to convert the southern campus into a designated hospital. Adult patients with underlying diseases. After the opening of the ICU on April 18 to treat severe and critically ill patients, Gao Yuan became the head here.
Gao Yuan is a “veteran” in the treatment of the new crown. After the outbreak of the new crown epidemic in 2020, he led Renji’s “Severe Illness Team” to enter the Shanghai Public Health Center and became the last evacuated intensive care team. Gao Yuan is very familiar with the changes in the treatment of the new crown in the past three years.
At the beginning of 2020, Gao Yuan led a team to support the Shanghai Public Health Center to take over the critically ill patient Lao Chen on the second day after participating in the treatment of severe patients with new crowns. Late that night, Lao Chen urgently went to ECMO (also known as “artificial lung”). At that time, new coronary pneumonia was a new disease, and everyone had not fully understood its pathology.
ECMO has been running for a long time, which has brought coagulation disorders to Lao Chen. Under normal circumstances, it can be alleviated by supplementing exogenous AT3 (antithrombin III), but exogenous plasma has no obvious effect on Laochen. At this critical moment, thanks to the strong support of Director Wang Xuefeng of Ruijin Hospital, he provided a new type of AT3 that was not available in China before, and corrected Lao Chen’s coagulation disorder.
However, due to the use of ECMO for more than 40 days, it is very difficult to perform muscle tremors and awakening on Lao Chen. During this process, his inflammatory reaction was severe, accompanied by severe coughing. Under the consultation of many experts, some effective methods were finally found to successfully wake up the patient completely.
After being admitted to the hospital for 73 days, he recovered and was discharged. Lao Chen became one of the critically ill patients with new coronary pneumonia who had the longest hospitalization time in Shanghai that year, and he used ECMO for more than 40 days. “ECMO took more than 40 days, far exceeding the frequency of daily treatment, which is unimaginable in normal times.” Gao Yuan said with emotion.
Based on people’s understanding of the new crown pneumonia at that time, the treatment of every critically ill patient with the new crown needs to challenge the existing medical limits and make continuous breakthroughs. Today, words like “white lung” are rarely heard, and most of the people who died of the new crown infection did not die of lung infection but other underlying diseases of the patient.
”In 2020, the lung infection of severe patients is relatively serious, and the team is often working hard to deal with the patient’s lung. Now, the situation is completely different.” Gao Yuan said that there are very few patients with severe lung infection caused by Omicron , but the strain is extremely transmissible, and people with serious underlying diseases are prone to develop severe disease after infection. This is the biggest challenge facing the treatment work now.
At two o’clock in the afternoon on April 23, Gao Yuan appeared in the conference room on time together with the directors of the infection department, respiratory department and other departments. Here, online consultations are held every afternoon. Doctors in the designated hospitals and experts from the parent hospital discussed the diagnosis and treatment plans for critically ill patients in the hospital one by one, and accurately formulated “one person, one policy”.
The patient discussed that day was in a complicated condition, suffering from mental illness, sudden acute myelitis, rhabdomyolysis, liver and kidney insufficiency, and later gastrointestinal bleeding, but the clinical symptoms of the new crown were mild, and CT showed a little lung ooze. After intense discussions, the directors of more than ten departments jointly formulated a new strategy.
”There are a large number of similar patients, and they have many underlying diseases, ranging from advanced tumors, cardiovascular diseases, nervous system diseases, severe immune system diseases to diabetes and hypertension, and more than half of the patients have three or more underlying diseases. The treatment is very complicated and requires the participation of multiple disciplines, strengthen the coordination of specialists, and treat one person with one plan to reduce the mortality rate.” Gao Yuan pointed out that compared with 2020, when treating critically ill patients, MDT (Multidisciplinary Diagnosis and Treatment) The role is more prominent.
Still need to make good use of “combination boxing”
The new crown virus is constantly mutating. Today, the elderly are undoubtedly the most dangerous group after being infected with the new crown virus. Not only in China, how to treat the elderly suffering from the new crown and the elderly with multiple underlying diseases is a major challenge for the world to deal with the new crown epidemic.
According to reports, in April, when the epidemic situation in Shanghai was the most severe this year, the proportion of patients over 60 years old in the ICU of Renjin South Hospital accounted for more than 80%, and patients over 80 years old accounted for more than 30%. Basic illness.
In addition to underlying diseases, the low vaccination rate among the elderly is also one of the reasons why the elderly have become the main group of severe cases of the new crown.
Even in Shanghai, vaccination coverage among the elderly is still low. On May 6, 2022, academician Chen Saijuan and Zhang Xinxin of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and Zhang Wenhong of Huashan Hospital Affiliated to Fudan University published a paper entitled “Shanghai’s response to the current COVID-19 crisis” in the top international medical journal “The Lancet”. Life-Saving Efforts from the Omicron Wave in the Epidemic”.
The article wrote that among Shanghai’s 5.8 million people over the age of 60, 62% had been vaccinated, while only 38% had received booster shots. As of May 4, 2022, of the 503 COVID-19 deaths, only 25 patients had received at least one dose of the COVID-19 vaccine. The vaccination rate of the deceased patients was only 4.97%.
In response to the current situation of epidemic prevention and control, the Comprehensive Group of the Joint Prevention and Control Mechanism of the State Council announced the “New Coronavirus Pneumonia Prevention and Control Plan (Ninth Edition)” in June this year, adjusted the prevention and control measures, and revised the “Citizens’ Basic Code of Conduct for Epidemic Prevention” Amended accordingly.
In 2020, the lung infection of severe patients is more serious, and the team is often working hard to deal with the patient’s lungs. Now, the situation is completely different.
The latest version of the code of conduct has 12 articles, including “vaccination” – vaccination is an effective means to block the spread of the new crown virus and prevent and control the new crown pneumonia epidemic. risk of death. People over the age of 60 who meet the vaccination requirements should complete the full vaccination as soon as possible and receive booster injections.
In April this year, the ICU of the southern branch (designated hospital) of Renji Hospital was officially opened.
Of course, specific drugs are always expected.
Ding Sheng, dean of the School of Pharmacy at Tsinghua University, believes that the long-term response to the new coronavirus requires a combination of vaccines and drugs, but they each play different roles. He further explained that vaccines are the most effective measure to deal with infectious diseases as a whole. It plays the role of identifying viruses and preventing infection; while anti-new crown drugs are used to treat new coronary pneumonia, which is a treatment option for people infected with new crown virus. Ding Sheng’s point of view has been recognized by many people in the industry.
As early as shortly after the outbreak of the epidemic in 2020, the research and development of new crown vaccines and specific drugs started globally. With the deepening of research, small-molecule drugs have shown unique advantages in the treatment of new crowns-the targets of small-molecule drugs can be distributed inside or outside cells; most small-molecule drugs can be administered orally; small-molecule drug preparation The process is relatively simple and mature, the yield is much higher than that of macromolecular biopharmaceuticals, and the cost is also lower than that of large molecules; the storage and transportation of small molecule drugs also require less environmental conditions, which is convenient for storage or transportation.
On March 14, 2022, the National Health and Medical Commission issued the “Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Ninth Edition)”. The latest version of the guidelines was unanimously considered by domestic experts to be the most scientific and effective version of the guidelines. Among them, the combined packaging of two specific drugs, Naimatevir Tablets/Ritonavir Tablets, and Ambavirumab/Romisvirumab Injection were included in the guidelines, pointing out the direction for clinical front-line doctors to use drugs.
Professor Zhang Jing, a doctoral supervisor at Fudan University and deputy director of the Institute of Antibiotics at Huashan Hospital affiliated to Fudan University, has participated in several important clinical research projects on new anti-new coronavirus drugs. The progress of viral drugs in scientific research and their entry into treatment guidelines.
According to Zhang Jing, the World Health Organization has updated the treatment guidelines for new coronary pneumonia in 2020, mainly based on the changes brought about by the mutation of the new coronavirus strain. more and more clinical attention.”
Zhang Jing further explained that small-molecule drugs have always been a mature and commonly used drug for diseases infected by pathogenic microorganisms such as bacteria, fungi, and viruses. Because small-molecule drugs have clear targets, they have won the trust of clinicians.
The small-molecule drug PAXLOVID TM that entered the ninth edition of China’s new crown diagnosis and treatment guidelines is not a single drug, but a combination of two drugs, Naimatevir Tablets and Ritonavir Tablets. “This design is ingenious. One drug targets the main protease target of the virus and blocks the replication of the virus; the second drug inhibits the metabolic enzyme in liver cells that can clear the previous drug, so that the previous drug molecule that inhibits the new coronavirus will not It will be quickly metabolized to ensure that it can play a better role in medicine.” Zhang Jing said.
After the outbreak of COVID-19, Professor Zhang Jing participated in the early clinical research of nucleic acid vaccines, anti-coronavirus neutralizing antibodies including monoclonal antibodies and double antibodies, and small molecule drugs. She said that from a historical perspective, infectious diseases have always been accompanied by the development of human beings. Viruses are constantly evolving. People need to continuously develop weapons to deal with viruses and promote human development in mutual games.
