Guidance for the management of adult patients with coronavirus disease 2019.

Abstract

In December 2019, a novel coronavirus was identified in Wuhan, Hubei Province, China.[1–3] On January 12, 2020, the World Health Organization (WHO) temporarily named the new coronavirus as “2019 novel coronavirus (2019-nCoV).” On February 8, the National Health Commission of the People's Republic of China announced that the name of the pneumonia caused by 2019-nCoV was “novel coronavirus pneumonia (NCP).” On February 12, Coronaviridae Study Group of the International Committee on Taxonomy of Viruses proposed to officially name the new coronavirus “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).” On the same day, the WHO announced the official name of the disease caused by the virus as “coronavirus disease 2019 (COVID-19).” On February 22, the National Health Commission of the People's Republic of China issued a notice to amend the English name of “NCP” to “COVID-19.”[4] Currently, although the epidemic situation in China is under control, the number of cases globally has been increasing. On March 11, 2020, the WHO officially announced that COVID-19 had reached global pandemic status. As experience and understanding of disease prevention, control, diagnosis, and treatment continue to accumulate, a summary of the results of available studies and experience is needed to guide the management of the disease. This guidance explains the up-to-date etiology, pathogenesis, epidemiology, clinical characteristics, treatment principles, rehabilitation, and prevention and control measures of COVID-19. Definition, Etiology, and Pathogenesis of COVID-19 Definition COVID-19 is an acute respiratory infectious disease caused by the newly emerging SARS-CoV-2. The incubation period of this disease is generally 1 to 14 days, and the main manifestations are fever, dry cough, and fatigue. Most patients have mild clinical symptoms and good prognosis; however, more severe cases can quickly deteriorate to acute respiratory distress syndrome (ARDS) and septic shock.[1] Furthermore, myocardial injury, acute kidney injury (AKI), and other organ dysfunction often occur in patients with severe disease.[2,3] Etiology In December 2019, after an unexplained viral pneumonia epidemic emerged in Wuhan, the National Health Commission designated the Chinese Center for Disease Control and Prevention, the Chinese Academy of Medical Sciences, the Academy of Military Medical Sciences of the Academy of Military Sciences, the Hubei Provincial Center for Disease Control and Prevention, and the Wuhan Institute of Virology, Chinese Academy of Sciences, among others, as parallel testing units. This combined effort resulted in the joint identification of a new type of coronavirus as the pathogen that caused the outbreak. On January 8, the results of the preliminary pathogen identification were announced, and the complete genome sequence of the virus was actively announced to the world.[2,5–7] The Coronaviridae Study Group of the International Committee on Taxonomy of Viruses named the virus SARS-CoV-2.[8] SARS-CoV-2 belongs to the β-coronavirus genus of coronaviruses, which is the same branch as severe acute respiratory syndrome coronavirus (SARS-CoV). Sequence alignment of the virus genome shows that SARS-CoV-2 is homologous to the SARS-CoV by approximately 79% and to the Middle East respiratory syndrome coronavirus (MERS-CoV) by only approximately 52%.[5] Similar to SARS-CoV, SARS-CoV-2 uses angiotensin-converting enzyme II (ACE2) as a receptor, which is widely distributed in many organs such as the lung, heart, kidney, and gastrointestinal tract.[7,9] Pathogenesis Although most patients infected with SARS-CoV-2 have only mild respiratory symptoms, the disease in approximately 5% of patients will progress to severe lung injury or even multiple organ dysfunction, with a mortality rate of 2%.[10] Until now, a substantial amount of research has been conducted in China. This has resulted in a basic understanding of the disease characteristics of COVID-19. However, the pathogenesis remains unknown, and further research is needed. Based on the recent findings of studies on SARS-CoV-2 and those of previous studies on SARS-CoV, we speculate that the pathogenesis of severe COVID-19 follows three potential mechanisms. (1) Direct infection by SARS-CoV-2 contributes to multiple organ damage. Electron microscopy of autopsy specimens has revealed a large number of virus particles in alveolar epithelial cells,[1] and live virus particles have also been isolated from respiratory specimens and urine and stool samples.[11,12] (2) An imbalance of the host immune response, characterized by cytokine storms and lymphopenia, is an important precursor of the onset of severe COVID-19.[2] (3) Multiple organ injury and coagulopathy caused by the virus also participate in the pathogenesis of severe COVID-19.[3] Pathological changes Autopsy and gross observation Following severe COVID-19, the lung lobes on both sides atrophy to varying degrees. On the cut surface, the lung air content decreases and solid changes are observed at varying degrees; no significant secretion is retained in the trachea, main bronchi, or lobar bronchi. Most patients have adhesions to the chest wall, especially in the middle and lower lobe of the lung. Light microscopic observation The main pathological changes noted in the lungs are a large number of macrophages and serous fibrous exudation in the alveolar cavity, accompanied with intra-alveolar hemorrhage [Figure 1]; diffuse alveolar damage, carnification in alveolar space, and pulmonary consolidation [Figure 2]; transparent membrane formation at alveolar cavity surface in some patients; Type II alveolar epithelium proliferation to varying degrees; alveolar septa widening to varying degrees and interstitial fibrous tissue proliferation, with a small amount of lymphocyte infiltration [Figure 3]; and retention of mucinous secretion and even mucus plugs in some small airways (mainly bronchioles and terminal bronchioles). Some patients have secondary bacterial infections, which are manifested as inflammatory cells, mainly neutrophils, infiltrating the lesion, and a few patients have secondary fungal infections, which are manifested as fungal mycelia and sporophytes in the lesion. These findings are consistent with viral pneumonia with or without secondary bacterial or fungal infection.Figure 1: Exudation of a large number of macrophages in the alveolar cavity and a small amount of lymphocyte infiltration in the alveolar septum (hematoxylin & eosin staining; original magnification ×200).Figure 2: Significant fibrotic proliferation and lung consolidation (hematoxylin & eosin staining; original magnification ×100).Figure 3: Widening of the alveolar septum with fibrotic proliferation (hematoxylin & eosin staining; original magnification ×100).Epidemiology of COVID-19 Source of infection Currently, it is believed that patients infected with SARS-CoV-2 are the main source of infection. Latent patients with no or mild transient symptoms may also become sources of infection. These patients are difficult to diagnose and isolate in a timely manner because they have no obvious symptoms. The accumulation of infectious sources at the community level has also hindered disease control. Current evidence suggests that patients in the incubation period may be infectious to some extent and that the presence of the virus can be detected in patients in the early recovery period, who may also be somewhat infectious.[1] Modes of transmission At present, respiratory droplets and close contact are considered to be the main route of transmission.[13] The virus is thus primarily transmitted through droplets produced by infected individuals when they cough and talk, and individuals who are susceptible become infected after inhaling these droplets. The droplets containing the virus can also be deposited on the surface of items and then transmitted to the mucous membranes of the mouth, nose, and eyes by contaminated hands and subsequently to the respiratory tract, where the infection develops. Aerosol transmission is also possible via prolonged exposure to high concentrations of virus aerosols in a relatively closed environment. As SARS-CoV-2 has also been isolated from feces and urine, there is a risk of fecal-oral transmission. A possible connection between environmental pollution caused by feces and urine and aerosol or contact transmission routes should be considered. Further studies are needed to determine whether mother-to-child transmission can occur. Susceptible populations As COVID-19 is a novel infectious disease, the global population lacks immunity to SARS-CoV-2, and thus, people of all ages are susceptible to infection. Elderly adults and people with comorbidities, such as chronic obstructive pulmonary disease, diabetes, hypertension, and heart disease, have an increased risk of infection. Close contacts with symptomatic and asymptomatic infected patients are at high risks of developing COVID-19. Medical staff is also at a higher risk of infection. Clinical Features of COVID-19 Clinical manifestation The incubation period is generally 3 to 7 days, with the shortest and longest known incubation periods of 1 day and 14 days, respectively. Acute onset of fever and fatigue occurs in the early stage, and the primary respiratory symptom is dry cough. A minority of patients also have symptoms of nasal congestion, runny nose, sore throat, muscle pain, and/or diarrhea. In severe cases, chest tightness and dyspnea may gradually develop after 7 to 10 days. ARDS, septic shock, metabolic acidosis that is particularly difficult to correct, and coagulation dysfunction can occur in critically ill patients. Notably, patients with severe illness can have moderate to low fever, even without obvious fever symptoms. Mild cases of infection generally manifest as low fever, fatigue, and no symptoms of pneumonia. Although most patients have a good prognosis, a few patients (approximately 5%) become critically ill and may die. Laboratory and radiological investigation General inspection In the early stage of the disease, the total number of white blood cells is normal or decreased, and the lymphocyte count is decreased. Some patients have increased levels of liver enzymes, muscle enzymes, and myoglobin. In most patients, C-reactive protein levels and erythrocyte sedimentation rates are elevated, and procalcitonin levels are normal. In severe cases, D-dimer levels are elevated, and inflammatory factors may also be elevated. Etiology and serology On etiological examination, SARS-CoV-2 nucleic acid can be detected in nasopharyngeal swabs, sputum, and other lower respiratory tract secretions, blood, stool, and other specimens using real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS). Detection with lower respiratory tract specimens (sputum and airway extracts) is more accurate. On serological examination, new specific immunoglobin M (IgM) antibodies are typically observed 3 to 5 days after onset, and the immunoglobin G (IgG) antibody titers in the recovery period are at least four times the amount in the acute phase. Chest imaging Multiple small patchy shadows and interstitial changes appear in the early stage and are obvious in the peripheral zone of lungs. These then develop into multiple ground-glass infiltrates in the lungs. In severe cases, pulmonary consolidation may appear, and pleural effusion is rare. Chest imaging findings are not specific and must be combined with clinical manifestations and dynamic observations. If short-term disease progression is obvious, the presence of multiple lung lesions is supportive of a definitive diagnosis; however, if the patient has an underlying lung disease, it is often difficult to distinguish viral lesions from other lung lesions, and thus, diagnosis must be confirmed with other tests.[1] Diagnosis of COVID-19 Etiological diagnosis Detection of SARS-CoV-2 nucleic acid using RT-PCR and/or NGS Various specimens, including nasopharyngeal swabs, sputum and other lower respiratory tract secretions, blood, and stool, are used to test positivity for SARS-CoV-2 nucleic acid, and positive findings can confirm viral infection. The most commonly used method for detecting nucleic acid is RT-PCR, which is the standard for COVID-19 etiological diagnosis. However, RT-PCR results can present with a false negative. SARS-CoV-2 infection mainly invades bronchial epithelial cells and alveolar epithelial cells; thus, lower respiratory tract specimens (ie, sputum or airway extracts) should be used to more accurately determine infection. Qualified sample collection, rapid delivery of specimens for inspection, standardized testing operation procedures, and use of standard-compliant test kits can effectively improve the accuracy of sample detection. In addition, nicking enzyme amplification reaction, which does not rely on the extraction of nucleic acids, can be used for rapid SARS-CoV-2 detection and screening. Serological detection of SARS-CoV-2 specific antibodies Most SARS-CoV-2-specific IgM antibodies are positive 3 to 5 days after onset. IgG antibody can serve as a confirmatory test when the titers in the recovery period are at least four times the amount in the acute phase. Enzyme-linked immunosorbent assay, the antibody gelatin method, and immunochromatography method can detect serum-specific IgM and IgG antibodies, with a sensitivity of 50% or more, and a specificity of 90% to 99%. The combined detection of IgM and IgG can improve diagnostic sensitivity. Serum antibody detection is a newly added evidence for etiological diagnosis in the “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7),”[1] and has the advantages of simplicity, rapidness, low price, and easy accessibility. Serum antibody detection can determine not only the presence of infection, but also the patient's immune status and can compensate when false-negative results of nucleic acid detection are observed, particularly in cases with low virus loads in the upper respiratory tract. Although serum antibody detection is an effective supplementary method for SARS-CoV-2 nucleic acid detection, there is an early window period in which serum antibodies cannot be detected. Additionally, this method has relatively low sensitivity, can only provide evidence of recent infection, and cannot confirm the presence of a live virus. Diagnostic criteria and systems The diagnosis of COVID-19 is based on a comprehensive diagnostic system of epidemiological history, clinical manifestations, and pathogenic confirmation. As a serious acute infectious disease, complete epidemiological history is particularly critical in the diagnosis of the disease. The average incubation period is 1 to 14 days, and a history of residence in or travel to Wuhan or severely infected areas within the past 14 days is an important epidemiological factor. The most common clinical manifestations are fever and respiratory symptoms such as dry cough and shortness of breath. More than 86% of patients also develop abnormalities visible on lung imaging. In addition to the typical manifestations of viral pneumonia (normal or decreased white blood cells), most COVID-19 cases are associated with decreased lymphocytes. Etiological confirmation of SARS-CoV-2 infection remains the gold standard for diagnosis. As asymptomatic viral carriers are also infectious and clustered onset has been observed, clinicians should pay close attention to it, which requires dynamic observation and repeated pathogenic examinations. The COVID-19 diagnostic criteria for suspected and confirmed cases are as follows.[1] Suspected cases For suspected cases, a comprehensive analysis of the following epidemiological history and clinical manifestations should be performed. Epidemiological history: (i) Travel history or residence history in Wuhan and surrounding areas or other communities with case reports within 14 days before onset; (ii) history of contact with SARS-CoV-2-infected persons (with positive nucleic acid test) within 14 days before onset; (iii) history of contact with patients from Wuhan and surrounding areas, or patients with fever or respiratory symptoms from a case-reporting community within 14 days before the onset of illness; and (iv) clustered cases. Clinical manifestations: (i) Fever and/or respiratory symptoms; (ii) characteristic imaging of COVID-19; and (iii) normal or decreased total number of white blood cells in the early stage of the disease and normal or decreased lymphocyte count. Patients who meet any one of the epidemiological items and any two of the clinical manifestations are suspected to have the disease. If there is no clear epidemiological history, three of the clinical manifestations should be met. Confirmed cases Suspected cases can be confirmed by one of the following pathogenic or serological positive results: (i) positive RT-PCR results for SARS-CoV-2 nucleic acid; (ii) viral gene sequencing highly homologous to the known SARS-CoV-2; or (iii) serum samples positive for SARS-CoV-2-specific IgM and IgG antibodies. The SARS-CoV-2-specific IgG antibody will need to change from negative to positive or the titers in the recovery period will need to be at least four times the amount in the acute phase. Severity classification The clinical classification of COVID-19 can be mild, moderate, severe, or critical.[1] (i) Mild: Clinical symptoms are slight, with no pneumonia manifestation on lung imaging. (ii) Moderate: Fever and respiratory symptoms with pneumonia manifestation visible on imaging; no dyspnea or other complications. (iii) Severe: Patients meet any of the following criteria: shortness of breath, respiratory rate (RR) ≥30 beats/min; resting state, mean oxygen saturation ≤93%; partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300 mmHg (1 mmHg = 0.133 kPa). At high altitudes (>1000 m), PaO2/FiO2 should be corrected according to the following formula: PaO2/FiO2 × [atmospheric pressure (mmHg)/760]; pulmonary imaging shows that the lesions have progressed by >50% within 24 to 48 h. (iv) Critical: Patients with one of the following conditions are considered critical: respiratory failure requiring mechanical ventilation; shock; and multiorgan failure requiring intensive care unit (ICU) monitoring and treatment. Risk factors for severe disease According to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7),[1] and the “Expert Consensus on Comprehensive Treatment of Coronavirus in Shanghai 2019,”[14] in combination with the latest clinical research,[3,15,16] we propose the following risk factors for severe COVID-19: (i) elderly patient (age >65 years); (ii) comorbidities, such as hypertension, diabetes, and coronary heart disease; (iii) progressive decline in peripheral blood lymphocytes, CD4+ T lymphocyte count <250/μL; (iv) progressive increase in peripheral blood inflammatory factors, such as interleukin (IL)-6 and C-reactive protein; (v) progressive increase in lactic acid and lactic dehydrogenase >2 times the upper limit of the normal value; (vi) intra-pulmonary lesions significantly progressed by >50% within 2 to 3 days; (vii) metabolic alkalosis; (viii) high sequential organ failure assessment scores; and (ix) D-dimer levels >1 mg/L at admission. Differential diagnosis Cases of mild COVID-19 should be distinguished from upper respiratory tract infections caused by other viruses, mainly common cold and influenza. Common cold primarily manifests with low fever and catarrhal symptoms, without seasonality, and although the population is generally vulnerable, it is typically self-limiting. Influenza[17] can cause more systemic symptoms, such as headache and myalgia, and influenza cases are the most prevalent from the end of November to the end of February of the following year. For moderate, severe, and critical cases with different levels of pulmonary infiltration, epidemiological and medical history, laboratory examination, and imaging findings should be incorporated to distinguish from other types of pneumonia caused by viral infections or atypical pathogens.[18] In particular, potential lung changes caused by non-infectious diseases should not be overlooked. Differential diagnoses of COVID-19 include: (i) Other viral pneumonia: The main viruses to be identified include influenza virus, human avian influenza virus, adenovirus, respiratory syncytial virus, MERS-CoV, and SARS-CoV. The diagnosis of COVID-19 should be based on a combination of epidemiological history (such as epidemic period and epidemic area travel history), clinical characteristics, and pathogenic examination results. (ii) Atypical pathogen pneumonia: This primarily includes lower respiratory tract infections caused by Mycoplasma, Chlamydia, and Legionella, which are mostly clustered. Irritating dry cough is a more characteristic clinical symptom of Mycoplasma infection, which is progressively aggravated. The clinical manifestations of Chlamydia pneumonia and Mycoplasma pneumonia are similar, and most cases have good prognosis. A small number of patients with Chlamydia psittaci infection can develop severe pneumonia. Epidemiological history of Legionella includes exposure to contaminated air conditioning systems or water sources, and the clinical manifestations include relatively slow pulse, fever, acute onset headache, non-drug-induced consciousness or drowsiness, non-drug-induced diarrhea, shock, acute liver and kidney damage, hyponatremia, and hypophosphatemia. (iii) Pulmonary changes caused by non-infectious factors: These include acute interstitial pneumonia, organizing pneumonia, pulmonary edema, alveolar hemorrhage, and secondary interstitial pneumonia caused by connective tissue disease. Detailed medical history, clinical manifestations, and specific laboratory indicators are required for definitive diagnosis. Treatment of COVID-19 General treatment Stratified treatment is based on the clinical severity of SARS-CoV-2 infection. The general treatment includes (i) proper bed rest, (ii) supportive treatments, such as maintaining a certain energy intake, water-electrolyte and acid-base balance, and the homeostasis of the internal environment; (iii) monitoring of vital signs, including body temperature, breathing, pulse, and blood oxygen saturation. Anti-viral treatment There are currently no specific anti-viral drugs for COVID-19. Based on the available evidence, the WHO lists candidate anti-viral drugs, including remdesivir, lopinavir/ritonavir, or lopinavir/ritonavir plus an interferon, that should be urgently evaluated.[19] Remdesivir has strong anti-viral activity against SARS-CoV-2 in vitro and shows good anti-viral effects in both severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) animal models.[20,21] Additionally, data from previous clinical trials show that remdesivir is well tolerated.[22] At present, two randomized controlled double-blind trials in China that include hospitalized patients with mild-to-moderate and severe COVID-19 are ongoing, with the aim of obtaining efficacy and safety results for remdesivir (NCT04252664, NCT04257656). The U.S. National Institutes of Health recently began a trial of remdesivir for hospitalized patients with COVID-19, and in March 2020, remdesivir received an orphan drug designation from the U.S. Food and Drug Administration. For lopinavir, there are no data regarding its efficacy against SARS-CoV-2 in vitro; however, there are available in vitro and in vivo data for both SARS and MERS.[23,24] In one study of 41 patients with SARS and 111 historical controls, the combination of lopinavir/ritonavir (in the study participants) was associated with significantly fewer adverse clinical outcomes than ribavirin alone (in the historical controls).[25] However, the historical nature of the control comparison in that study does not allow for a valid estimate of efficacy. In 2016, Arabi et al[26] launched a randomized controlled trial (RCT) of lopinavir/ritonavir combined with interferon-β in patients with MERS-CoV in the Kingdom of Saudi Arabia (NCT02845843). In a randomized, controlled, open-label trial conducted by the community-acquired pneumonia-China network and involving hospitalized adult patients with confirmed SARS-CoV-2 infection, no benefit was observed in the primary endpoint of time to clinical improvement, but the results for certain secondary endpoints were intriguing (ChiCTR2000029308).[27] Future trials in patients with COVID-19 may help confirm or exclude the possibility of treatment benefits with lopinavir/ritonavir. Common adverse events of lopinavir/ritonavir include gastrointestinal tract reactions, and attention should be paid to the interaction between lopinavir/ritonavir and other drugs metabolized by cytochrome P450. Favipiravir and ribavirin are nucleoside analogs, and in vitro data have confirmed that ribavirin has weak anti-viral activity against SARS-CoV and MERS-CoV. The median effective concentration (EC50) of favipiravir against the SARS-CoV-2 in vitro was 61.88 μmol/L.[28] In theory, high blood concentrations of favipiravir would be required to achieve anti-viral effects in patients with COVID-19. At present, a historical cohort study and a preprint paper of an RCT reported mild clinical benefits of favipiravir treatment for COVID-19. In addition, some experts have proposed using Arbidol to treat COVID-19; however, its anti-viral mechanism against the coronavirus is unclear. In brief, further RCTs are needed to clarify the efficacy and safety of potential anti-viral agents against SARS-CoV-2. Anti-bacterial treatment The irrational use of anti-microbials should be avoided, and a combined approach to anti-microbial stewardship program (ASP) and COVID-19 prevention and control has been recommended.[29] Senior infectious disease experts and qualified clinical pharmacists are both core members of a hospital ASP team and will also have actively participated in the epidemic response and institutional preparation. An expert team can identify early potential cases, the microbiology laboratory team can identify pathogens, and the anti-infective clinical pharmacist can help develop anti-microbial treatment programs, monitor and manage drug shortages owing to insufficient supply during an epidemic, and coordinate front-line access to new drugs in epidemic areas. It is not recommended to use anti-bacterial drugs to treat mild cases of COVID-19. Antibiotics can be used to treat severely and critically ill patients with COVID-19 and pre-existing or secondary bacterial and/or fungal infections. Appropriate respiratory pathogen detection should be improved, including the detection of other respiratory viruses, bacterial smears and cultures, and fungal tests. Empirical treatment should refer to local pneumonia epidemiology and surveillance data of bacterial or fungal resistance. When sepsis is present, antibiotics should be administered within 1 h of the initial patient evaluation,[30] and step-down treatment should be administered in a timely manner according to microbiological results and clinical consultations.[1,30] The irrational use of anti-bacterial drugs in the management of patients with COVID-19 will increase the risk of nosocomial infections from drug-resistant bacteria, as well as the risk of early lymphocyte decline in severely or critically ill patients. High-risk factors for secondary invasive fungal infections include the use of high-dose glucocorticoids, long-term stays in the ICU, and receiving non-invasive or invasive mechanical ventilation.[31] The guidelines for hospital-acquired pneumonia and invasive fungal infection should be followed, and drugs should be selected rationally. Immunomodulatory therapy Glucocorticoids The use of glucocorticoids in the treatment of COVID-19 is controversial because no relevant RCTs have been conducted. Studies have shown that low and medium doses of glucocorticoids can reduce mortality and shorten hospital stays in patients with severe viral pneumonia without inducing secondary infection or other complications.[32] The “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)”[1] of the National Health Commission recommends that glucocorticoids should be used as appropriate in the short term for patients with progressive deterioration of oxygenation indicators, rapid disease progression on imaging findings, and excessive activation of inflammatory response. Domestic retrospective studies in China have shown that low and medium doses of glucocorticoids have no significant effect on viral clearance time. A potential benefit of glucocorticoids in critically ill patients may exist.[33] Given the current limited evidence, glucocorticoids should be used with caution in the management of COVID-19, and the indications and contraindications must be strictly adhered to. The specific recommendations for glucocorticoid use are as follows.[34] Principles: (i) Use glucocorticoids with caution, and prohibit the use of glucocorticoids to reduce fever and (2) for patients who have regularly used glucocorticoids before SARS-CoV-2 infection for autoimmune diseases, nephrotic syndrome, bronchial asthma, and other underlying diseases, the dosage of glucocorticoids should be individualized according to the patient's underlying disease and the severity of the infection. Indications: (i) Imaging-confirmed pneumonia and rapid progression (lesion progression >50% within 24 to 48 h); (ii) blood oxygen saturation (SpO2) ≤93% or respiratory distress (RR ≥30 breaths/min) or oxygenation index ≤300 mmHg breathing room air in a resting state. Both of these conditions must be met simultaneously to justify glucocorticoid use. Contraindications: Caution is required for patients with