Professor Mu Xiangdong
Mu Xiangdong, Director of the Department of Respiratory and Critical Care Medicine, Beijing Tsing Hua Chang Gung Memorial Hospital; Chief Physician; Professor and Mentor to Graduate Students; First Deputy Director of the Youth Committee; Member of the Youth Committee of the Chinese Thoracic Society; Member of the Infectious Disease Committee of the Chinese Thoracic Society; President of the Bronchiectasis Respiratory Committee of the Wu Lien-Teh Public Foundation.
Introduction: If patients infected with COVID-19 are found to have a significant increase in their white blood cells, neutrophils and procalcitonin (PCT) values, a timely etiological examination should be completed, and appropriate antibacterial treatment should be initiated.
While the peak of severe COVID-19 infection has subsided, antiviral and anti-inflammatory treatments for infected patients continue to require special clinical attention. The incidence of varying degrees of pulmonary fibrosis in the late stage of severe COVID-19 pneumonia is almost 100%.1 In order to provide better treatment for infected patients, the Respiratory Center of Beijing Tsinghua Chang Gung Memorial Hospital recently published the “Concise Diagnosis and Treatment Recommendations for Pulmonary Fibrosis After COVID-19 Pneumonia (1st Edition)”.1
“Medical World” recently invited Professor Mu Xiangdong from Beijing Tsinghua Chang Gung Memorial Hospital to speak on the evolution and virulence of the Omicron strain, the clinical diagnosis and treatment of new COVID-19 pneumonia, and to elaborate further on the necessity of anti-inflammatory and antibacterial treatment for infected patients.
Q1. Omicron has become the dominant variant around the world. What are your thoughts regarding the change in its virulence? BA.5.2 and BF.7 are the dominant subvariants in the North and South. Are there differences in their virulence and the clinical symptoms caused by each?
With continuous spread and mutation, Omicron has evolved into many subvariants. Current data show that the main mutant strains prevalent in Beijing and Guangzhou are BF.7 and BA.5.2, respectively. As both are subvariants of Omicron and share a close evolutionary relationship, they are also very similar in terms of viral genome sequence and pathogenicity. At present, a significant difference can be seen between the clinical manifestations of COVID-19 patients in the North and South. Patients in Guangzhou, in particular, mostly have mild symptoms or are asymptomatic, whereas the percentage of asymptomatic patients in northern China is relatively low. The clinical manifestations of infected patients in the North are also more obvious, especially upper respiratory tract symptoms.
This is not because the virulence of the Omicron variant is “stronger in the North and weaker in the South,” but rather the result of differing clinical manifestations at different stages of the disease after infection, which are caused by the difference in temperature. It should be noted that human immunity is closely related to temperature. At present, the temperature in the North is generally below zero degrees Celsius. Not only does the cold climate greatly impact human immunity, it also exacerbates the clinical manifestations of patients with cardiovascular and cerebrovascular diseases, respiratory diseases (such as chronic obstructive pulmonary disease [COPD]), diabetes and other diseases. Even if infected with the same strain of COVID-19, the symptoms of patients will differ at contrasting temperatures.
In addition, when the prevention and control strategy was first implemented, COVID-19 had yet to become a full-blown pandemic and few critically ill patients were clinically diagnosed. However, 1–2 weeks after the course of the patient’s illness and as the pandemic continued to develop within the community, the number of critically ill patients in both the North and the South increased sharply. The similar spike in cases between regions indicates some similarity of the impact of Omicron in both areas, so the reasons behind the difference should not be generalized until the full picture has been understood.
Q2. Are there any differences in the imaging of COVID-19 pneumonia compared with general influenza pneumonia?
Compared with influenza pneumonia, COVID-19 pneumonia is “simpler”. In terms of imaging, COVID-19 pneumonia has “less heterogeneity and stronger characteristics,” which makes it relatively easier to identify and is conducive to clinical diagnosis.
Pneumonia caused by influenza virus is more complicated. On the one hand, the influenza virus itself can cause viral pneumonia, while on the other, it can lead to decreased immune function of patients followed by secondary bacterial pneumonia. Clinically, some patients with influenza pneumonia were found to also have severe bacterial infections such as Staphylococcus aureus and Streptococcus pneumoniae.
Patients infected with COVID-19 have relatively fewer bacterial infections. Although secondary bacterial infections may occur as the disease progresses, the prevalence is not as high as that seen with influenza pneumonia. In imaging, COVID-19 patients with pneumonia are seen with multiple patchy ground-glass opacity in both lungs that are mainly distributed in the subpleural area. As the disease progresses, reverse pulmonary edema symptoms may appear.
Q3. After being severely infected with COVID-19 for more than 5–7 days, attention should be paid to anti-inflammatory treatment, especially for patients with ‘cytokine storms.’ Based on your clinical experience, could you explain how people with a higher incidence of cytokine storms can be identified? How should the timing of anti-inflammatory treatment be determined? How should the success or failure of anti-inflammatory treatment be evaluated?
Severe COVID-19 pneumonia generally goes through three stages: viral replication, pulmonary inflammation, and pulmonary fibrosis. For these three stages, antiviral, anti-inflammatory and anti-fibrosis treatments should be carried out, respectively. However, these three stages cannot be completely separated, therefore, the treatment regimen needs to be an individualized combination plan based on the patient’s condition. During the viral replication period, the patient’s symptoms are mainly concentrated in the upper respiratory tract. As the disease progresses, the infection will spread to the lungs. After 5–7 days of infection, the patient is usually experiencing lung inflammation. The viral replication period has not ended at this point in time, as it is still replicating further in the lower respiratory tract and causing inflammation.
Clinical observations have found that virus can still be detected in the lower respiratory tract even after testing negative for the virus in the upper respiratory tract. Therefore, it is very important to carry out antiviral treatment during the pulmonary inflammation period 5–7 days after severe infection. It has also been found that, compared with patients who do not receive antiviral treatment, patients who receive antiviral treatment in the late stage of severe COVID-19 saw more clinical benefits.
Compared with other types of pneumonia, the inflammatory response caused by COVID-19 is more severe. The inflammatory response is closely related to the patient’s condition, so doctors should look into the severity of the patient’s condition when evaluating the necessity and timing of anti-inflammatory treatment. Secondly, inflammatory factors such as interleukin 6 (IL-6), C-reactive protein (CRP) and PCT all reflect the severity of the patient’s inflammation to a certain extent, and thus may also be used as reference indicators. In addition, one of the main features of patients with viral pneumonia is dyspnea, which is not the case for bacterial pneumonia. Therefore, the severity of inflammation can also be determined by observing whether the patient needs oxygen supplementation to relieve the symptoms of dyspnea.
Anti-inflammatory treatments are mainly divided into broad-spectrum anti-inflammatory drugs and targeted anti-inflammatory drugs. In the case of unidentified inflammatory pathways, broad-spectrum anti-inflammatory drugs can be used. This includes glucocorticoids, the classic broad-spectrum anti-inflammatory drug widely used in clinical practice. If the main pathway of the patient’s inflammatory response has been determined, specific targeted anti-inflammatory drugs such as the IL-6 antagonist tocilizumab, can be used to inhibit the excessive inflammatory response of critically ill patients. Anti-inflammatory drugs can also be used in combination.
It is worth noting that anti-inflammatory treatment can lead to a decline in immunity, but the virus can only fundamentally be defeated through the strengthening of the immune system. In other words, anti-inflammatory treatment and antiviral treatment have an inherently contradicting but unifying relationship. Therefore, anti-inflammatory treatment should be provided “adequately.” Clinically, small to medium doses of hormone therapy are generally used and the course of treatment in the acute phase takes approximately 7–14 days. If the patient’s condition still recurs after treatment, anti-inflammatory treatment can be restarted. At this stage, a reduced dosage of anti-inflammatory drugs should be taken.
Q4. After being infected with COVID-19, under what circumstances can the patient begin antibiotic treatment? How should patients with different clinical manifestations choose from various antibiotic treatment options? In the initial empiric treatment, respiratory quinolones and second-generation cephalosporins are the first choice. Based on your clinical experience, could you please elaborate on the applicable population, treatment timing and clinical value of respiratory quinolones (such as levofloxacin, moxifloxacin and sitafloxacin)?
Aside from some patients with bacterial sinusitis and otitis media, the prevalence of COVID-19 and upper respiratory tract bacterial co-infection is generally low, and most patients do not require antibacterial treatment. In terms of treatment of pulmonary infection, it is generally not necessary to initiate antimicrobial therapy for young patients with pneumonia who do not have underlying diseases. For patients at high risk of bacterial infection and who are concurrently complicated with bronchitis, bronchiectasis, COPD, diabetes and other common diseases, especially those over 65 years old, a sputum sample should be sent for culture and etiological examination if the patient’s white blood cells, neutrophils, PCT value and other indicators are found to be significantly increased. After the pathogenic bacteria is identified, antibiotics should be rationally used for treatment according to the drug susceptibility results.
Patients that were in the community prior to infection and admitted to the hospital within 48 hours are clinically treated according to the community-acquired pneumonia (CAP) management plan. For the treatment of CAP, respiratory quinolones such as levofloxacin, moxifloxacin, and sitafloxacin are the first choice, though macrolides or tetracyclines can also be used. If necessary, β-lactam antibacterial drugs are used in combination, to ensure protection against Gram-positive cocci and atypical pathogens. For patients that are hospitalized for more than 48 hours, protection against Gram-negative bacilli and multidrug-resistant bacteria are considered according to the hospital-acquired pneumonia (HAP) protocol.