Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition)
Since December 2019, a novel coronavirus pneumonia epidemic has appeared in Wuhan City, Hubei Province. With the spread of the epidemic, other cities in China and many countries abroad have also found such cases. As an acute respiratory infectious disease, the disease has been included in the Class B infectious diseases stipulated in the Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases, and is managed as a Class A infectious disease. Through the adoption of a series of preventive control and medical treatment measures, the upward trend of the epidemic situation in China has been contained to a certain extent. The epidemic situation in most provinces has eased, but the number of outbreaks abroad is on the rise. With the deepen understanding of the clinical manifestations, pathological features of this disease and the accumulation of experience in diagnosis and treatment, in order to further strengthen the early diagnosis and early treatment of the disease, improve the cure rate, reduce the mortality rate, and avoid in-hospital infection, and alert for the disease transmission caused by overseas input cases, we revised the previous clinical guidance to form this 7th version.
The novel coronavirus (termed as COVID-19 by World Health Organization) belongs to the corona-virus βgenus, which is encapsulated in round or oval shape, and 60-140mm in diameter. The genetic characteristics of COVID-19 are significantly different from SARS-CoV and MERS-CoV. It shares more than 85% homology with SARS-Iike coronavirus isolated from bat (bat-SL-CoVZC45). The COVID-19 can be detected in human respiratory epithelial cells for about 96 hours in vitro, but it takes about 6 days to isolate and culture in Vero E6 and Huh-7 cell lines.
Our current understandings on the biochemical features of COVID-19 are mostly derived from previous studies on SARS-CoV and MERS-CoV. COVID-19 is fragile to ultraviolet and heat (56℃ for 30 minutes). It can also be inactivated by liposoluble solvents, such as ether, 75% ethanol (w/v), chlorine-containing disinfectant and chloroform. However, chlorhexidine has been proved generally ineffective.
a) Source of infection
Infected patients (symptomatic or asymptomatic) are the main source of infection.
b) Route of transmission
COVID-19 is transmitted through respiratory droplets and close contact. Aerosol transmission is plausible when patients are exposed to high concentration virus-containing aerosols for a long period of time and in a relatively closed environment. In addition, because COVID-19 has been isolated from stool and urine specimens, special attention should be paid to human waste disposal to avoid direct contact and/or environment contamination.
c) Susceptible population
Human beings are generally susceptible to COVID-19.
The following summary is based on limited numbers of autopsy and biopsy findings.
Lung consolidation was observed in various degrees.
Fibrinous exudation and hyaline membrane formation were filled in alveolar cavity. Exudative cells mainly consist of mononuclear cells and macrophages. Polynuclear gian cells were prominent. Type II alveolar epithelial cells were markedly proliferated, and some were detached into alveolar cavity. Inclusion bodies were found in type II alveolar epithelial cells and macrophages. Hyperemia and edema were apparent in alveolar septal areas. Mononuclear cell and lymphocyte infiltration, intravascular hyaline thrombosis, focal hemorrhage and necrosis of lung tissue could be seen, and hemorrhagic infarction occurred. Pathological features of organizing pneumonia and pulmonary interstitial fibrosis could be observed in pulmonary parenchyma.
Intrapulmonary bronchial epithelial cells were detached, and bronchial cavity was filled with mucus plugs. In some area, pulmonary alveoli were hyperinflated, alveolar septa fractured, and cystic cavities formed.
Coronavirus particles were found in the cytoplasm of bronchial epithelium and type II alveolar epithelial cells under electron microscope. Immunohistochemical staining showed that some alveolar epithelial cells and macrophages were positive for COVID-19 antigens. COVID-19 nuclear acids were detected through RT-PCR.
b) Spleen, hilar lymph nodes, and bone marrow
Spleen was markedly shrunk, in which lymphocytes were significantly reduced in numbers, with apparent focal hemorrhage and necrosis. Macrophage proliferation and phagocytosis were also observed. In lymph nodes, lymphocytes were also depleted and necrotized. In addition, immunohistochemical staining showed that the number of CD4+ T and CD8+ T cells in both spleen and lymph nodes were significantly decreased. All hematopoietic cell linages were reduced in bone marrow.
c) Cardiovascular svstem
It was found that some cardiomyocytes were degenerated and necrotized, and a small number of monocytes, lymphocytes and/or neutrophils are infiltrated in the myocardium. In some areas, vascular endothelial cells were detached where inflammation and thrombosis occurred.
d) Liver and gallbladder
Liver was characterized by increased volume, dark red color, hepatocyte degeneration, focal necrosis with neutrophil infiltration, hepatic sinus congestion, infiltration of lymphocytes and monocytes in the portal area, and microthrombus formation. Gallbladder was also significantly increased in size.
Protein exudate was found in Bowman’s capsules. Renal tubular epithelium was denatured and exfoliated, and hyaline cast was formed. Interstitial hyperemia, micro thrombus and focal fibrosis could be seen.
f) Other organs
The brain tissue was congested and edematous, and some neurons were degenerated. Focal necrosis was observed in the adrenal gland. The epithelium of esophagus, stomach and intestines were denatured, necrotic and exfoliated with different degrees.
4. Clinical features
a) Clinical manifestation
Based on the current epidemiological survey, the incubation period of COVID-19 is 1-14 days. Most patients show clinical symptoms in 3-7 days.
Fever, dry cough, and fatigue are the main manifestations. Other symptoms include nasal obstruction, runny nose, sore throat, myalgia and diarrhea. In severe cases, patients presented dyspnea and/or hypoxemia within one week after onset. Some of them rapidly deteriorated to acute respiratory distress syndrome (ARDS), septic shock, refractory metabolic acidosis, coagulation dysfunction, and multiple organ failure. Notably, some severe patients only presented mild- to moderate-grade fever in their entire course of disease, and some even did not show fever at all.
Some children and newborns presented atypical symptoms, such as vomiting, diarrhea and other gastrointestinal discomfort, or only exhibited drowsiness and shortness of breath.
In mild cases, patients only presented low-grade fever and slight fatigue, without evident pneumoma.
From our current observation, most patients have a good prognosis, and only a few patients are critically ill. The prognosis for the elderly and those with chronic comorbidities is relatively worse. The clinical course of COVID-19 pneumonia in pregnant women is similar to that of the same age group. The severity of symptoms in children is relatively mild.
b) Laboratory examination
i. Routine examination
In the early stage of the disease, the total count of peripheral leukocytes could be normal or decreased, and the lymphocyte decreased. In some patients, liver transaminases, lactate dehydrogenase (LDH), creatine kinase and myoglobin were elevated. In some critically severe patients, troponins were also increased. In most patients, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were increased, while procalcitonin generally remains in normal range. Notably, D-dimer was significantly increased in severe patients, and peripheral lymphocytes were progressively decreased. Inflammatory biomarkers are often elevated in severe and critically severe patients.
ii. Etiological and serological examination
(1) Etiological examination: COVID-19 nucleic acids can be detected in nasopharyngeal swabs, sputum and other lower respiratory tract secretions, blood and feces by using RT-PCR and next generation sequencing technology(NGS). It is more accurate to detect the lower respiratory tract specimen (sputum or airway extract). Once collected, specimen examination should be performed as soon as possible.
(2) Serological examination: the COVID-19-specific IgM antibody starts to show positive after 3-5 days from onset. In comparison, the titer of COVID-19-specific IgG antibody is 4 times higher in recovery period than that in acute phase.
iii. Chest imaging
At the early stage of the disease, multiple small patchy shadows and interstitial changes appear, which are more obvious in the periphery of the lung. Then it developed into multiple ground-glass shadows and infiltrates shadows. In severe cases, pulmonary consolidation may occur. Pleural effusion is rare.
5. Diagnostic criteria
a) Suspected cases
Comprehensive analysis of the following epidemiological history and clinical manifestations :
i. Epidemiological history
(1) Travel or residence history of Wuhan and surrounding areas, or other communities with documented COVID-19 positive cases within 14 days before the onset of illness.
(2) History of contact with COVID-19-infected persons (positive for nucleic acid detection) within 14 days before the onset of illness.
(3) History of contact with the patients presenting fever or respiratory symptoms,who travel to or reside in Wuhan and surrounding areas, or in other communities with documented COVID-19 positive cases within 14 days before the onset of illness.
(4) Clustering onset (2 or more cases of fever and/or respiratory symptoms within 2 weeks in small areas such as home. office. school class. etc.)
ii. Clinical manifestation
(1) Presenting with fever and/or respiratory symptoms.
(2) With imaging features of above mentioned COVID-19 pneumoma.
(3) In the early stage of the disease, the total number of leukocytes was normal or decreased, and the lymphocyte count was normal or decreased.
A case that meets any one of the epidemiological history criteria and any two of the clinical manifestations can be identified as a suspected case. If there is no clear epidemiological history, 3 of the clinical manifestations is required.
b) Confirmed cases
Suspected cases with one of the following etiology or serological evidence can be identified as confirmed cases:
(1) Real-time RT-PCR detection is positive for COVID-19 nucleic acid.
(2) The viral gene identified by gene sequencing is highly homologous with known COVID-19;
(3) The COVID-19-specific IgM and IgG antibodies are tested positive. The titer of COVID-19-specific IgG antibody is 4 times higher in recovery period than that in acute phase.
6. Clinical classification
a) Mild type
The clinical symptoms are mild. and there was no sign of pneumonia on chest imaging.
b) Moderate type
These patients had fever and respiratory symptoms. Radiologic assessments found signs of pneumoma.
c) Severe type
Adults meet any of the following criteria:
(1) Shortness of breath, RR≥30 times/min;
(2) Oxygen saturation≤93% at rest;
(3) Alveolar oxygen partial pressure/fraction of inspiration O₂ (PaO₂/FiO₂) ≤300 mmHg (lmmHg=0.133 kPa).
At high altitudes (above 1000 meters), PaO₂/FiO₂should be corrected according to the following formula: PaO₂/FiO₂x[Atmospheric Pressure (mmHg)/760] .
Patients whose pulmonary imaging showed significant progression of lesion>50% within 24-48 hours should be treated as severe type.