Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)

Abstract

Since December 2019, multiple cases of novel coronavirus pneumonia (COVID-19) have been identified in Wuhan, Hubei. With the spread of the epidemic, such cases have also been found in other parts of China and other countries. As an acute respiratory infectious disease, COVID-19 has been included in Class B infectious diseases prescribed in the Law of the People's Republic of China on Prevention and Treatment of Infectious Diseases, and managed as an infectious disease of Class A. By taking a series of preventive control and medical treatment measures, the rise of the epidemic situation in China has been contained to a certain extent, and the epidemic situation has eased in most provinces, but the incidence abroad is on the rise. With increased understanding of the clinical manifestations and pathology of the 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, avoid nosocomial infection as much as possible and pay attention to the spread caused by the imported cases from overseas, we revised the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 6) to Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). I. Etiological Characteristics The novel coronaviruses belong to the β genus. They have envelopes, and the particles are round or oval, often polymorphic, with diameter being 60 to 140 nm. Their genetic characteristics are significantly different from SARS-CoV and MERS-CoV. Current research shows that they share more than 85% homology with bat SARS-like coronaviruses (bat-SL-CoVZC45). When isolated and cultured in vitro, the 2019-nCoV can be found in human respiratory epithelial cells in about 96 hours, however, it takes about 6 days for the virus to be found if isolated and cultured in Vero E6 and Huh-7 cell lines. Most of the knowledge about the physical and chemical properties of coronavirus comes from the research on SARS-CoV and MERS-CoV. The virus is sensitive to ultraviolet and heat. Exposure to 56°C for 30 minutes and lipid solvents such as ether, 75% ethanol, chlorine-containing disinfectant, peracetic acid, and chloroform can effectively inactivate the virus. Chlorhexidine has not been effective in inactivating the virus. II. Epidemiological Characteristics 1. Source of infection Currently, the patients infected by the novel coronavirus are the main source of infection; asymptomatic infected people can also be an infectious source. 2. Route of transmission Transmission of the virus happens mainly through respiratory droplets and close contact. There is the possibility of aerosol transmission in a relatively closed environment for a long-time exposure to high concentrations of aerosol. As the novel coronavirus can be isolated in feces and urine, attention should be paid to feces or urine contaminated environment that may lead to aerosol or contact transmission. 3. Susceptible groups People are generally susceptible. III. Pathological Changes Pathologic findings from limited autopsies and biopsy studies are summarized below: 1. Lungs Variable consolidation is present in the lungs. The alveoli are filled with fluid and fibrin with hyaline membrane formation. Macrophages and many multinucleated syncytial cells are identified within the alveolar exudates. Type II pneumocytes show marked hyperplasia and focal desquamation. Viral inclusions are observed in type II pneumocytes and macrophages. In addition, there is prominent edema and congestion in the alveolar septa which are infiltrated by monocytes and lymphocytes. Fibrin microthrombi are present. In more severely affected area, hemorrhage, necrosis, and overt hemorrhagic infarction are seen. Organization of alveolar exudates and interstitial fibrosis are also present. Detached epithelial cell and mucus are present in the bronchi, sometimes mucus plugs are seen. Hyperventilated alveoli, interrupted alveolar interstitium, and cystic formation are occasionally seen. By electronic microscopy, cytoplasmic 2019-nCoV virions are observed in the bronchial epithelium and type II pneumocytes. Immunostain reveals 2019-nCoV viral immunoreactivity in some alveolar epithelial cells and macrophages and RT-PCR confirms the presence of 2019-nCoV nucleic acid. 2. Spleen, hilar lymph nodes, and bone marrow The spleen is markedly atrophic with a decreased number of lymphocytes. Focal hemorrhage and necrosis are present. Macrophages proliferation and phagocytosis are present in the spleen. Sparsity of lymphocytes and focal necrosis are noted in lymph nodes. CD4+ and CD8+ immunohistochemistry highlights a decreased number of T cells in the spleen and lymph nodes. Myelopoiesis is decreased in bone marrow. 3. Heart and blood vessels Degenerated or necrosed myocardial cells are present, along with mild infiltration of monocytes, lymphocytes, and/or neutrophils in the cardiac interstitium. Shedding of endothelial cells, endovasculitis, and thrombi are seen in some blood vessels. 4. Liver and gall bladder The liver is dark-red and enlarged. Degeneration and focal necrosis of hepatocytes are found, accompanied by infiltration of neutrophils. The sinusoids are congested. The portal areas are infiltrated by lymphocytes and histiocytes. Microthrombi are seen. The gallbladder is prominently distended. 5. Kidneys The kidneys are remarkable for proteinaceous exudates in the Bowman's capsule around glomeruli, degeneration, and shedding of renal tubules epithelial cells, and hyaline casts. Microthrombi and fibrotic foci are found in the kidney interstitium. 6. Other organs Cerebral hyperemia and edema are present, with degeneration of some neurons. Necrotic foci are noted in the adrenal glands. Degeneration, necrosis, and desquamation of epithelium mucosae of variable degree are present in the esophageal, stomach, and bowel. IV. Clinical Characteristics 1. Clinical manifestations Based on the current epidemiological investigation, the incubation period is one to 14 days, mostly three to seven days. The main manifestations include fever, fatigue, and dry cough. Nasal congestion, runny nose, sore throat, myalgia, and diarrhea are found in a few cases. Severe patients develop dyspnea and/or hypoxemia after one week and may progress rapidly to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulopathy, multiple organ failure etc. It is noteworthy that for severe and critically ill patients may only present with moderate to low fever, or even no fever at all. Some children and neonatal patients may have atypical symptoms, presented with gastrointestinal symptoms such as vomiting and diarrhea, or only manifested as lethargy and shortness of breath. The patients with mild symptoms usually do not develop pneumonia but have low fever and mild fatigue. Based on our experience, most patients have good prognosis and a small percentage of patients are critically ill. The prognosis for the elderly and patients with chronic underlying diseases is poorer. The clinical course of pregnant women with COVID-19 is similar to that of non-pregnant patients of the same age. Symptoms in children are relatively mild. 2. Laboratory tests General findings In the early stages of the disease, peripheral WBC count is normal or decreased and the lymphocyte count is decreased. Some patients have elevated liver enzymes, lactate dehydrogenase (LDH), muscle enzymes and myoglobin. Elevated troponin is seen in some critically ill patients. Most patients have elevated C-reactive protein and erythrocyte sedimentation rate and normal procalcitonin. In severe cases, D-dimer increases and peripheral blood lymphocytes progressively decrease. Severe and critically ill patients often have elevated inflammatory factors. Pathogenic and serological findings (1) Pathogenic findings: Novel coronavirus nucleic acid can be detected in nasopharyngeal swabs, sputum, lower respiratory tract secretions, blood, feces, and other specimens using RT-PCR and/or NGS methods. It is more accurate if specimens are obtained from lower respiratory tract (sputum or air tract extraction). The specimens should be submitted for testing as soon as possible after collection. (2) Serological findings: COVID-19 virus specific IgM becomes detectable around 3–5 days after onset; IgG reaches a titration of at least 4-fold increase during convalescence compared with the acute phase. 3. Chest imaging In the early stage, imaging shows multiple small patchy shadows and interstitial changes, more apparent in the peripheral zone of lungs. As the disease progresses, imaging shows multiple ground glass opacities and infiltration in both lungs. In severe cases, pulmonary consolidation may occur. However, pleural effusion is rare. V. Case Definitions 1. Suspect cases Considering both the following epidemiological history and clinical manifestations: 1.1 Epidemiological history 1.1.1 History of travel to or residence in Wuhan and its surrounding areas, or in other communities where cases have been reported within 14 days prior to the onset of the disease; 1.1.2 In contact with novel coronavirus infected people (with positive results for the nucleic acid test) within 14 days prior to the onset of the disease; 1.1.3 In contact with patients who have fever or respiratory symptoms from Wuhan and its surrounding area, or from communities where confirmed cases have been reported within 14 days before the onset of the disease; or 1.1.4 Clustered cases (2 or more cases with fever and/or respiratory symptoms in a small area such families, offices, schools etc within 2 weeks). 1.2 Clinical manifestations 1.2.1 Fever and/or respiratory symptoms; 1.2.2 The aforementioned imaging characteristics of COVID-19; 1.2.3 Normal or decreased WBC count, normal or decreased lymphocyte count in the early stage of onset. A suspect case has any of the epidemiological history plus any two clinical manifestations or all three clinical manifestations if there is no clear epidemiological history. 2. Confirmed cases Suspect cases with one of the following etiological or serological evidences: 2.1 Real-time fluorescent RT-PCR indicates positive for new coronavirus nucleic acid; 2.2 Viral gene sequence is highly homologous to known new coronaviruses. 2.3 COVID-19 virus specific IgM and IgG are detectable in serum; COVID-19 virus specific IgG is detectable or reaches a titration of at least 4-fold increase during convalescence compared with the acute phase. VI. Clinical Classification 1. Mild cases The clinical symptoms were mild, and there was no sign of pneumonia on imaging. 2. Moderate cases Showing fever and respiratory symptoms with radiological findings of pneumonia. 3. Severe cases Adult cases meeting any of the following criteria: (1) Respiratory distress (≥30 breaths/min); (2) Oxygen saturation ≤93% at rest; (3) Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300 mmHg (1 mmHg = 0.133 kPa). In high-altitude areas (at an altitude of over 1000 meters above the sea level), PaO2/FiO2 shall be corrected by the following formula: Cases with chest imaging that shows obvious lesion progression within 24–48 hours >50% shall be managed as severe cases. Child cases meeting any of the following criteria: (1) Tachypnea (RR ≥ 60 breaths/min for infants aged below 2 months; RR ≥ 50 BPM for infants aged 2–12 months; RR ≥ 40 BPM for children aged 1–5 years, and RR ≥ 30 BPM for children above 5 years old) independent of fever and crying; (2) Oxygen saturation ≤92% on finger pulse oximeter taken at rest; (3) Labored breathing (moaning, nasal fluttering, and infrasternal, supraclavicular, and intercostal retraction), cyanosis, and intermittent apnea; (4) Lethargy and convulsion; (5) Difficulty feeding and signs of dehydration. 4. Critical cases Cases meeting any of the following criteria: 4.1 Respiratory failure and requiring mechanical ventilation; 4.2 Shock; 4.3 With other organ failure that requires ICU care. VII. Clinical Early Warning Indicators of Severe and Critical Cases 1. Adults 1.1 The peripheral blood lymphocytes decrease progressively; 1.2 Peripheral blood inflammatory factors, such as IL-6 and C-reactive proteins, increase progressively; 1.3 Lactate increases progressively; 1.4 Lung lesions develop rapidly in a short period of time. 2. Children 2.1 Respiratory rate increased; 2.2 Poor mental reaction and drowsiness; 2.3 Lactate increases progressively; 2.4 Imaging shows infiltration on both sides or multiple lobes, pleural effusion or rapid progress of lesions in a short period of time; 2.5 Infants under the age of 3 months who have either underlying diseases (congenital heart disease, bronchopulmonary dysplasia, respiratory tract deformity, abnormal hemoglobin, and severe malnutrition, etc.) or immune deficiency or hypofunction (long-term use of immunosuppressants). VIII. Differential Diagnosis 1. The mild manifestations of COVID-19 need to be distinguished from those of upper respiratory tract infections caused by other viruses. 2. COVID-19 is mainly distinguished from other known viral pneumonia and mycoplasma pneumoniae infections such as influenza virus, adenovirus and respiratory syncytial virus. For suspect cases, efforts should be made to use methods such as rapid antigen detection and multiplex PCR nucleic acid testing for detection of common respiratory pathogens. 3. COVID-19 should also be distinguished from non-infectious diseases such as vasculitis, dermatomyositis, and organizing pneumonia. IX. Case Finding and Reporting Health professionals in medical institutions of all types and at all levels, upon discovering suspect cases that meet the definition, should in for and the cases are as after made by or it should be reported within 2 should be for new coronavirus nucleic acid testing and suspect cases should be to the People who have been in close contact with confirmed patients are to new coronavirus testing in a even common respiratory are two nucleic acid taken at least of an COVID-19 suspect case are and the COVID-19 virus specific IgM and IgG are after days from the suspect diagnosis can be Treatment 1. Treatment by the of the disease 1.1 and confirmed cases should be isolated and at with effective and in A suspect case should be in in a Confirmed cases can be in the same 1.2 Critical cases should be to ICU as soon as 2. General treatment 2.1 patients in and for and to environment signs and oxygen 2.2 to blood urine C-reactive protein myocardial renal blood chest and detection if 2.3 effective oxygen nasal and and nasal oxygen of and oxygen can be 2.4 can or for 2 of for two no than to be with or for or three of no than for days for aged with over 50 for 2 and for for with below 50 for no than of the be for patients with heart and of the the of those being three or more at the same is not if an the should be For the treatment of pregnant such as the number of of the least on the as as being before treatment should be with patients being of 2.5 or use of should be in with 3. 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The use of the of from a small and the to the of the The is as Viral infection or mild plus or or plus 40 fever with of of and of inflammatory multiple organ of and of of with of or of period Lung and spleen deficiency Clinical manifestations: shortness of fatigue, and The is and 30 6 6 with of taking of the in the and the other in the of both and Clinical manifestations: shortness of dry low or no fever, dry dry or 6 6 6 with of taking of the in the and the other in the and 1. is to normal for more than 3 Respiratory symptoms improve imaging shows obvious of acid tests on respiratory tract such as and nasopharyngeal being at least who meet the above can be 2. 2.1 The should contact the where the patients and share medical to the of the patients to the and where the patients it is for patients to in for 14 days, a in if close contact with and avoid 2.3 It is for the patients to to the for and in two and after should be in with the Protocol for of the Novel Coronavirus Pneumonia (Trial by the Health Prevention and to and control nosocomial infection should be in with the of the for the Prevention and of by the Novel Coronavirus in and the on the of Novel Coronavirus (Trial by the Health The General of Health of and on The and Treatment for is at The was through in China and the are the of the

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