Author: QIU Jia (MD Weekly)
Translator: COVID-19 Readings
In this battle with the virus, the medical workers are the soldiers who rushed ahead.
As the director of the emergency department of Wuhan Union Medical College Hospital, Professor Zhang Jinnong was one of the first doctors to contact patients with COVID-19 and actively carry out clinical diagnosis and treatment. He also became one of the earliest medical workers infected with COVID-19 due to long hours of heavy work and close contact with patients.
The dual status of doctor and patient gave Zhang Jinnong more perspectives and more treatment plans to try and implement. He first advocated home isolation for mild cases, and based on his own experience, made public recommendations for home isolation.
Zhang Jinnong did not stop working during the illness. He remotely read the scans, discussed cases, participated in consultations. With in-depth front-line clinical experience, a large amount of literature review and contemplation, he drafted the “Wuhan Union Hospital 2019 Novel Coronavirus Infection Treatment Strategies and Instructions”, which is the country’s first guidance program for the diagnosis and treatment of COVID-19, affectionately called the “Wuhan Union Program”. It provided great reference for the diagnosis and treatment of COVID-19, reducing the severity and mortality, improving the cure rate, and the formulation of subsequent national diagnosis and treatment plans. The treatment and triage strategy was published online on February 13 in The Lancet Respiratory Medicine.
MD Weekly reporter connected exclusively with Professor Zhang Jinnong to introduce the essence of thinking and treatment characteristics of “Wuhan Union Treatment Program”.
Antivirals Must Be Given Early, They Are Only Effective Within 72 Hours
Zhang Jinnong told the reporter that their first batch of 15 medical staff who had been infected were all cured and discharged, and he was the last one to be discharged. These medical staff all adopted the “Wuhan Union Medical Treatment Program”, none of them became severely ill, no one was on the ventilator, and rarely took oxygen. Generally, the inflammation indicators were all normal within two weeks, and nucleic acid testing results turned negative in about 20 days.
The formulation of the “Wuhan Concorde Treatment Program” was based on considerations about the characteristics of the novel coronavirus. Professor Zhang introduced that this novel coronavirus pneumonia is in line with the characteristics of respiratory viral pneumonia. Like influenza and SARS, it can lower the overall system immunity, and lymphocyte decline is a very accurate indicator. Secondly, the local defense function of the respiratory tract is destroyed.
“As a patient, I clearly felt the dry throat and no sputum. This indicates that the mucociliary clearance mechanism was damaged. Currently, the virus is mainly found in the alveoli. This is strikingly similar to the previous reports of autopsy of patients who died from influenza, which showed that the virus was not only in the upper respiratory tract, but had also entered the alveoli.”
Professor Zhang therefore believes that the research on influenza in these years can be used for reference. For example, previous studies have shown that oseltamivir is effective against the influenza virus, but it needs to be used early. It will not be effective by the time the virus destroys the local respiratory tract and systemic immunity. Therefore, neuraminidase inhibitors such as oseltamivir are only conditionally effective for influenza and must be used within 72 hours.
“So I predict that the current antiviral drugs that people generally think might be effective, whether it is Remdesivir, Cliz, or Abidol, must be used early, otherwise there will be no obvious effect like with the flu.” Professor Zhang thinks that currently the designated hospitals are all treating severely ill patients, studies on the efficacy of the antiviral drugs may not yield good results.
Why Did I Choose Abidol?
Professor Zhang said that many antiviral drugs have shown very good results in vitro. Remdesivir, the frontr unner, is naturally the focus. However, the problem is that Remdesivir is a new drug that has not been on the market, much less having post-market observations. Without studies with real-world big data, its safety cannot be determined.
“Currently, the mortality rate is only 2% in areas where the mortality rate is low, and some provinces do not even have any deaths. For such a disease, how do we consider the use of new drugs with unclear safety profile, long-term side effects and possible damage to human health? Is it worth it? So I very much agree with what Academician Zhong Nanshan said, it is necessary to follow the procedure and complete the tests step by step. Do not use it on a large scale in the beginning. “
At present, according to reports in The Cell journal in the United States, chloroquine is the second most effective for the novel coronavirus. Chloroquine has been reported to cause adverse reactions such as cardiac arrest, large-scale application may also require caution. “But at least we have previous experience with chloroquine and know what the side effects are.”
In third place is Abidol, with an in vitro selection index for influenza virus of 2.5 and in the same batch of tests an index of 8.6 for coronaviruses. It has been clinically proven to be effective in treating flu and rhinovirus, so wouldn’t it be more effective for coronavirus? Professor Zhang said that the drug is only available in China and Russia. It has been used in Russia for 30 years and has proven to be without side effects. In the current trial usage against COVID-19, it is also well tolerated. What needs to be made clear is that a high therapeutic index does not necessarily mean it will be clinically effective.
“In contrast, the Remdesivir therapeutic index is as high as a few hundred, but can it be proven effective? At the time it was certainly effective in vitro against the Ebola virus, but later it had no effect when used on Africans. These are all worth considering.”
The Key to Reducing The Severity / Mortality of COVID-19 Is to Treat Secondary Bacterial Infections
Attaching importance to “virus induced secondary bacterial infections” is an issue that Professor Zhang Jinnong has been emphasizing, and the treatment of secondary bacterial infections is also the core of “Wuhan Union Treatment Program”.
“The efficacy of specific antiviral drugs depends on the time of administration. The sooner the better, otherwise the immune system will already have been destroyed. Viral infections lead to a decrease in the body’s immunity and it is very common for patients to have bacterial infections.”
Professor Zhang gave the reporter several typical examples. AIDS patients, due to HIV infection causing the body’s immunity to decline, usually will have combined bacteria (such as tuberculosis) and other pathogenic microorganism (such as pneumocystis) infections.
In 1918, there were no antibacterial drugs in the world. Some literature suggested that the autopsy of 8,000 cases of death from the 1918 influenza showed that all were due to bacterial infections, so that at that time, the flu was thought to be caused by bacteria. At that time, a German scientist cultivated this bacterium after adding blood to the medium, so it was called Haemophilus influenzae, which is a common colonizing bacteria in the human upper respiratory tract mucosa.
Rhinoviruses cause colds, and colds can easily cause acute episodes of chronic obstructive pulmonary disease (COPD). Haemophilus influenzae, a colonic bacteria of the respiratory tract mucosa, is the main cause of chronic obstructive pulmonary disease. This shows that rhinovirus infection induces bacterial co-infection, which leads to the acute attack of COPD.
“We may not have a specific medicine for treating viral infections, but we have corresponding antibacterial drugs for treating bacterial infections.” Professor Zhang said that autopsy results of 2009 influenza deaths showed that 50% had bacterial infections. There were two main pathogenic bacteria, one was Streptococcus pneumoniae, and the other was Staphylococcus aureus. Because we talked about the similarity of respiratory viruses before, this time for COVID-19 we should also focus on the secondary infection of these two bacteria.
Strep. pneumoniae is very resistant to penicillin. For penicillin-resistant Strep. pneumoniae, carbapenems or macrolides are not used. The Wuhan Union Treatment Program recommends respiratory quinolones, followed by ceftriaxone, and number 3 is amoxicillin. Quinolone should not be used in pregnant women. Ceftriaxone is preferred.
A prospective study published by Chinese scholars internationally showed that the most effective respiratory quinolones for Strep. pneumoniae were moxifloxacin and levofloxacin, which were almost 100% sensitive, followed by ceftriaxone, which was 70% sensitive. The third place was amoxicillin, 50% sensitive.
Staph. aureus is a very important pathogen in severe pneumonia. All international guidelines, expert recommendations, articles published by authoritative magazines, etc. emphasize that (treating) severe pneumonia should cover Staph. aureus. Staph. aureus is a common pathogen in community-acquired pneumonia (CAP). Severe patients often have Staph. aureus infections. Staph. aureus is very toxic and produces leukotoxins, causing severe inflammatory reactions.
“Right now, everyone has been referring to an inflammatory storm (cytokine storm) 7 to 10 days into the illness. The popular explanation is the systemic inflammatory response plus organ damage, which is sepsis. It is not that the virus invades your liver, kidney, and heart, then a large amount of inflammation causes organ damage, instead often bacterial infection peaks in 7 to 10 days.” Therefore, Professor Zhang said that in clinical treatment, there has to be awareness of the necessity of controlling Staph. aureus in critically ill patients.
“So we must suppress these common CAP pathogenic bacteria. Without infection or reducing the infection, the inflammatory storm will be mild and no sepsis will occur. Without sepsis, there will be no organ damage and no organ damage, once the patient has survived 7 to 10 days, then it will be immune victory in 14 to 21 days! “
Professor Zhang said that most patients without severe complications were cured in two to three weeks. In these two to three weeks, remove the virus as soon as possible, control bacterial infections, start empirical antibacterial treatment early, provide respiratory support if there is respiratory failure, minimize the patient’s inflammatory response. Corticosteroids or gamma globulin should be used with caution to prevent immune closure. Try not to interfere with the patient’s immune reconstruction process. This is the “Wuhan Union Treatment Program”.
Achieve Three Preventions
How to prevent COVID-19 has been the focus of attention. Professor Zhang Jinnong suggested that the “prevention” here should include preventing those who are not infected from infection, prevent infected patients from getting worse, and prevent cured patients from “relapse”.
“The country has implemented a series of measures to prevent infection. Our hospitals require wearing a mask from beginning to end and improving air circulation. Our front-line doctors are actually at high risk. The gathering of a large number of patients leads to extremely high viral titre, greatly increasing the risk of infection.”
Professor Zhang believes that attention should also be paid to the issue of fecal-oral transmission. “Currently, the International Virus Classification Commission proposes to name the novel coronavirus SARS-CoV-2, mainly because it is considered to be very similar to SARS. There had been reports of faecal-oral transmission for SARS previously.
In addition, COVID-19 patients had symptoms of diarrhea, and I myself also had symptoms of diarrhea. Therefore, I discussed with Professor Tang Chengwei, director of the Department of Gastroenterology at West China Hospital, to quickly check the patients’ stool to see if it would test positive in nucleic acid tests, and it turned out to be positive indeed.” Professor Zhang said that this was why he chose to use Abidol himself. The concentration of Abidol in the lungs is not as high as that in the hepatobiliary system, so it should be more effective on the digestive system. His own experiment did prove it to be effective.
The prevention for patients is mainly to prevent or reduce secondary CAP, to reasonably apply antibacterial treatment, to discharge as soon as possible, to prevent bacterial cross infection, and to be alert to the occurrence of hospital-acquired pneumonia (HAP). The pathogenic bacteria of HAP are usually drug-resistant. In addition to worsening the condition, the disease will also be more difficult to treat.
For patients who were cured and discharged, Professor Zhang said that attention should still be paid to home isolation. “Although I was discharged from the hospital, I still needed to isolate at home for 14 days according to requirements.” Professor Zhang believes that the so-called “relapse prevention” does not mean that the patient will be re-infected with the virus. Because the body will produce a certain amount of antibodies, it is unlikely to be re-infected by the virus in the short term. But because of the patient’s declined immunity, it is necessary to guard against the possibility of re-infection with CAP.
Handbook of COVID-19 Prevention and Treatment (The First Aliated Hospital, Zhejiang University School of Medicine)