Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 9th Version)

Abstract

In order to further improve the diagnosis and treatment of COVID-19, we organized experts to revise the relevant content of the Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 8th Version), and developed the Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 9th Version). Etiological characteristics The 2019-nCoV (also as SARS-CoV-2) belongs to the beta genus of coronaviruses. It has an envelope, round or oval particles, and a diameter of 60 to 140 nm. It has 5 essential genes, respectively targeting RNA-dependent RNA polymerase and 4 structural proteins of nucleoprotein (N), envelope protein (E), matrix protein (M), and spike protein (S). The N protein wraps the RNA genome to form a nucleocapsid, which is surrounded by an E that contains the M and the S proteins. The S protein enters the cell by binding to angiotensin converting enzyme 2 (ACE-2). When isolated and cultured in vitro, the 2019-nCoV can be found in human respiratory epithelial cells in about 96 hours, while it takes about 4 to 6 days to isolate and culture in Vero E6 and Huh-7 cell lines. The 2019-nCoV, like all other viruses, mutates, and certain mutations may affect the biological characteristics of the virus. For example, the change in the binding affinity of the spike protein and ACE-2 may affect the virus's ability of cell invasion, replication, and transmission, as well as period of recovery, antibodies produced after vaccination, and the neutralizing ability of antibody therapeutics. Therefore, such mutation has attracted wide attention. There are five “variants of concern” defined by the World Health Organization (WHO), namely Alpha, Beta, Gamma, Delta, and Omicron. At present, the Omicron variant has quickly replaced the Delta variant to become the dominant variant. Currently available evidence shows that the Omicron variant is more transmissible than the Delta variant, but with weakened pathogenicity. Omicron variant does not impact SARS-CoV-2 detection capability of RT-PCR assays diagnostic, but it may reduce the neutralizing effect of some monoclonal antibody drugs. Coronavirus is sensitive to ultraviolet rays and heat. 56°C for 30 minutes alone, ether, 75% ethanol, chlorine-containing disinfectant, peracetic acid, chloroform, and other lipid solvents can effectively inactivate the virus, while chlorhexidine cannot. Epidemiological characteristics Source of infection The source of infection is mainly patients infected with the 2019-nCoV as well as asymptomatic carriers. Patients are infectious during the incubation period and are highly infectious within 5 days after the onset of disease. Route of transmission (1) The 2019-nCoV is spread through respiratory droplets. Close contact among people is the main route of transmission. (2) The virus may spread through aerosols in a relatively closed environment. (3) Contact with items contaminated by the virus can also cause infection. Susceptible population Everyone is susceptible to 2019-nCoV. Infection or vaccination can acquire certain immunity. Pathological changes The followings are pathological changes in major organs caused by the 2019-nCoV, along with the testing results (excluding underlying diseases). Lungs In the early and mild lesions, serous fluid, fibrin exudation, and hyaline membrane formation can be seen in the alveolar cavity, and the inflammatory cells are mainly monocytes and lymphocytes. The alveolar septal capillaries were congested. With the progression and aggravation of the lesion, a large number of monocytes/macrophages and fibrin fill the alveolar space. Type II alveolar epithelial cells proliferate, and some shedding of cells occurs as well. Multinucleated giant cells are found, and red-stained inclusion bodies are occasionally seen. It is easy to find pulmonary vasculitis, thrombosis (mixed thrombus, clear thrombus), and thromboembolism. Part of the epithelium of the bronchial mucosa in the lungs shed, and exudates and mucus are detected in the cavity. Exudate and mucus are seen in the small bronchi and bronchioles. Small bronchi and bronchioles are prone to mucus plugging. Focal hemorrhages are common in lung tissue, and hemorrhagic infarcts, bacterial and/or fungal infections can be seen. Partial alveolar hyperinflation, rupture of alveolar septa, or cyst formation are seen. Alveolar space exudate fleshy change and pulmonary fibrosis are found among the patients with long course of disease. Under the electron microscope, coronavirus particles are found in the bronchial mucosal epithelium and cytoplasm of type II alveolar epithelial cells. Immunohistochemical staining shows that 2019-nCoV antigen immunostaining and nucleic acid detection are positive in some bronchial epithelial cells, alveolar epithelial cells, and macrophages. Spleen, hilar lymph nodes, and bone marrow The spleen atrophies. White pulp, and the lymphocytes are reduced, and some of these cells are necrotic. Hyperemia is found in the red pulp and focal hemorrhage can occur. Macrophages in the spleen proliferate and phagocytosis is visible. Splenic anemic infarction can appear. Lymph nodes can have fewer lymphocytes and necrosis can be seen here. Immunohistochemical staining shows that CD4+ T and CD8+ T cells in the spleen and lymph nodes are reduced. Lymph node tissue can be positive for the 2019-nCoV nucleic acid test, and immunostaining for the 2019-nCoV antigen of macrophages is positive. Bone marrow hematopoietic cells may proliferate or decrease in number, and the proportion of red granules increases; hemophagocytosis is occasionally seen. Heart and blood vessels Some cardiomyocytes can show degeneration, necrosis, interstitial congestion, or edema, and monocyte, lymphocyte and/or neutrophil infiltration. Occasionally, the 2019-nCoV nucleic acid test is positive. Endothelial cell shedding, intimal or full-thickness inflammation can be observed in small blood vessels throughout the body. Mixed thrombosis, thromboembolism, and infarction in corresponding parts can be detected in blood vessels. Visible thrombosis can be seen in the micro vessels of the main organs. Liver and gallbladder Hepatocyte degeneration and focal necrosis with neutrophil infiltration can be seen, as well as liver sinusoid congestion, lymphocyte, and monocyte cell infiltration in the portal area, and microthrombus formation. The gallbladder is fully expanded, with gallbladder mucosal epithelial shedding. The liver and gallbladder show positive nucleic acid tests for the 2019-nCoV. Kidneys Glomerular capillary congestion, and segmental fibrinoid necrosis are occasionally observed. Protein exudates are seen in Bowman's space. The proximal tubules have degeneration of the epithelium, with some necrosis and shedding, and the casts in the distal tubules are easily observed. The renal interstitium can be congested, and microthrombos is identifiable. Kidney tissue occasionally tests positive for the 2019-nCoV nucleic acid. Other organs Brain tissue congestion and edema, some neuronal degeneration, ischemic changes and loss, and occasional phagocytic phenomenon and satellite phenomenon can be detected, along with visible infiltration of monocytes and lymphocytes in the perivascular space. The epithelium of the esophagus, stomach, and intestinal mucosa show degeneration, necrosis, and shedding to varying degrees, and the lamina propria and submucosal monocyte and lymphocyte infiltration is observed. Cortical cell degeneration, focal hemorrhage, and necrosis are evident in the adrenal glands. In the testes, the number of spermatogenic cells decrease in varying degrees, and Sertoli cells and Leydig cells show degeneration. The 2019-nCoV can be detected in the nasopharynx and gastrointestinal mucosa, testes, salivary glands, and other organs. Clinical features Clinical manifestations The incubation period is 1 to 14 days, mostly 3 to 7 days. Main symptoms are fever, dry cough, and fatigue. Some patients may present with nasal congestion, runny nose, sore throat, decreased or lost sense of smell and/or taste, conjunctivitis, myalgia, and diarrhea. Severe patients often develop dyspnea and/or hypoxemia within one week after the onset. Critically ill cases can quickly progress to acute respiratory distress syndrome, septic shock, irreversible metabolic acidosis, coagulation dysfunction and multiple organ failure. A very small number of patients may also have central nervous system involvement and macrovascular necrosis. It is worth noting that severe and critically ill patients may only have low to moderate fever, or even no fever during the course of disease. Mild patients may present with low fever, mild fatigue, olfactory and gustatory disorders, and without pneumonia. Some patients may also have no obvious clinical symptoms after 2019-nCoV infection. Those who have been vaccinated and those infected with Omicron variant are mainly asymptomatic and mild. Patients with clinical symptoms mainly manifest with upper respiratory tract infection symptoms such as low to moderate fever, dry throat, sore throat, nasal congestion, and runny nose. Most patients have a good prognosis, with a few patients are critically ill. Most of the critically ill patients are more common in elderly, those with chronic underlying diseases, women in late pregnancy and perinatal period, or obese people. Symptoms in children are relatively mild. Some children and newborns may have atypical symptoms, such as vomiting, diarrhea and other gastrointestinal symptoms, or only poor response and shortness of breath. A very small number of children may have multiple system inflammatory syndrome (MIS-C) with Kawasaki disease-like or atypical Kawasaki disease manifestation, toxic shock syndrome or macrophage activation syndrome, mostly in recovery period. The main manifestations are fever with rash, non-purulent conjunctivitis, mucosal inflammation, hypotension or shock, coagulopathy, acute gastrointestinal symptoms, etc. Once this occurs, the condition can deteriorate sharply in a short period of time. Laboratory diagnosis General testing In the early stage of the disease, peripheral white blood cell counts is normal or decreased as well as the lymphocyte count. Some patients may have increased liver enzymes, lactate dehydrogenase, muscle enzymes, myoglobin, troponin and ferritin. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) is elevated and normal procalcitonin level in most patients. Severe and critically ill patients can show increased D-dimer level, a progressive decrease in lymphocyte counts and increased level of inflammatory factors. Etiology and serological examination Pathogenic test Real time reverse transcription-polymerase chain reaction (RT-PCR) testing of samples from and respiratory tract samples and acid testing can be by the course of disease, testing and testing In order to improve the of be in a and for as as after examination The antibody and antibody are and the positive rate is low within 1 week onset. to the positive of the or the of in the or the cause of the of the bacterial of the time of the coagulation of the the antibody test may show serological testing is not as a alone, and be in with clinical and underlying In the early multiple small and interstitial changes are seen, in the of the it multiple and infiltration in Severe cases can show lung but is In patients with and dysfunction can show and pulmonary Diagnosis Diagnosis be a of of clinical and A positive nucleic acid test for the coronavirus is the for For those who have not been vaccinated the 2019-nCoV, the detection of antibodies can be as a for For those who have been vaccinated or infected with the 2019-nCoV, in antibodies are not as the for cases of the and clinical is no clear of the clinical or have of the clinical manifestations and the antibody is positive for vaccinated Epidemiological (1) or in a with within 14 days the (2) A of contact with patients with 2019-nCoV infection within 14 days of the (3) Contact with patients with fever or respiratory symptoms from with within 14 days of the disease or more cases of fever and/or respiratory symptoms in small such as within 14 days. Clinical manifestations (1) and/or respiratory symptoms and other clinical manifestations to (2) characteristics of (3) The number of white blood cell is low or normal early and lymphocyte is low or cases cases with one of the or serological (1) A positive time RT-PCR detection of the 2019-nCoV nucleic (2) The antibody and antibody test is positive for the Clinical Mild The clinical symptoms are and is no in With the clinical pneumonia. Severe one of the (1) of (2) In the the is while (3) of of In with than be to the The clinical symptoms are and lung shows that the has within to of the (1) fever more than 3 (2) of 60 1 to 5 30 of fever and (3) In the the is while distress to or with of one the (1) and (2) (3) to other organ failure. with of than 60 the such as chronic lung diseases, chronic liver or disease, of or other that to pregnancy and perinatal for The be to the (1) or progressive of respiratory (2) of tissue or progressive in (3) decrease of peripheral blood lymphocyte or an in inflammatory such as and of D-dimer and coagulation an obvious progression pneumonia. (1) (2) response and (3) in lactate of and other inflammatory or multiple lung or progression of the disease in a short period of time in disease, respiratory severe of and diagnosis The mild manifestations of 2019-nCoV be from upper respiratory tract infections caused by other The caused by 2019-nCoV to be from other virus, respiratory virus, and infection. for antigen testing and multiple nucleic acid detection be as as for testing of common respiratory from such as vasculitis, and pneumonia. with and mucosal be from Kawasaki disease. The contact of COVID-19 even with a positive of common respiratory and a or a positive that the all for 2019-nCoV nucleic acid testing or cases to the of the of and and For the one with positive be isolated in the or to the for and be in with the cases with results for nucleic acid tests can be for infection. Treatment and condition Mild cases are The be for and other the time. the period, patients the treatment and the condition it be to a for and cases with of critically ill be in the Severe and cases be to as early as and patients with and severe also be to General treatment and to the of and to in and after blood enzymes, enzymes, blood coagulation blood to the testing is nasal and nasal to of the of drugs. treatment are COVID-19 patients within 5 days of disease onset and of severe disease. of with one of for five days. The be and it not be in with such as and which are highly for and can to and/or in for and with mild to moderate COVID-19 and of severe disease. are a of with of normal the are by a rate of not than 4 and of normal is to the in patients during and 1 after for COVID-19 can be among patients with in the early stage of disease. The for the mild is for the moderate and for the severe The can be the the of the with the number not It can be in patients with a and disease progression in the early stage of disease. The is to to 5 to be to the and For patients with progressive of and inflammatory can be for a short to 5 days, and no more than The for is 5 and and of be to reduce for patients with severe and patients with elevated The is with the of to to and the time of more than 1 the is not the can be after the The number of is 2 and the does not be in such as For the moderate with and disease severe and critically ill of low or be is no Treatment be in of to the The moderate with and disease severe and critically ill be prone with than Patients often have and be and with treatment treatment of severe and cases Treatment and underlying diseases, and organ the or Patients with than Patients who a nasal or be for respiratory distress and/or hypoxemia does not nasal or be or Patients with than or that patients or prone for is no Some patients have of or treatment failure. patients and be is no in hypoxemia or the of or patients have or after the prone treatment within hours, be the is than in patients with and be in of the atypical clinical manifestations of hypoxemia in severe and critically ill in time in with clinical manifestations and organ other than for and It is worth noting that the of may cause and is for critically ill patients. be can be in patients with moderate to severe acute respiratory distress syndrome with a than pulmonary the lung It be that some patients with COVID-19 have poor lung and be to an and for and are such as and is and be as as to and pulmonary in the of and membrane patients who the of 6 and no and prone one of be to as as (1) 3 (2) 6 (3) blood and for more than 6 hours, and respiratory rate blood and the Critically ill patients who the treatment as as is no is the most for respiratory is for patients who respiratory and be the is in patients be after rate prone for patients is to or with a obvious of the of the or of ability is than that of and more sensitive to to more and than The be of the lungs is not Critically ill patients can be with the of be rate and as well as acid and be be and renal Critically ill patients can be with acute Some such as and low are to and acid while the cause of for renal (1) (2) severe (3) pulmonary or with inflammatory syndrome The treatment is shock and coagulation organ and treatment is the for those without shock When the condition does not or and other with is the for patients with severe children be with shock or with such as Severe or cases with pregnancy be for The pregnancy be is the be with a of and protein be can be can be to intestinal and bacterial infection. disease belongs to in caused by the factors. to the and of and the treatment Protocol may The of be by a Clinical and gastrointestinal or Clinical and fever clinical treatment of It is for moderate and severe and can be in with the of patients in the treatment of critically ill patients. 6 6 6 6 6 for in with of the in the and in the minutes after with days a course of the can a of time after the and can to one the has a dry and is in the does not have a fever, the of be a fever or fever, the of can be the symptoms improve but not fully the course of the has or other underlying diseases, the of the course of treatment can be the and the be the symptoms of for in 2 for days. Mild cases (1) and lung syndrome Clinical fever, fatigue, sore cough, of vomiting, has or is and the is white or white and the is or to 6 30 and with of the in the and in the respectively to can be moderate patients. (2) and lung syndrome Clinical low or no fever, fatigue, and muscle dry cough, sore throat, dry without of or by no or or and of diarrhea or The is and the is and or and the is or 5 with of the in the and the other in the it with a 3 a The course of treatment is days. a a The course of treatment is days. a 3 a for and 3 time. The the of and The of is the for 30 minutes a cases (1) and lung syndrome Clinical fever, and or shortness of and The is red and the is or and the is or and 6 30 30 30 30 with of the in the and the other in the it with one a a The course of treatment is days, or the (2) lung syndrome Clinical low fever, fever or of fever, dry cough, fatigue, and in the stomach, or The is or and the is white or and the is 6 6 one with of the in the and the other in the (3) and syndrome Clinical fever, muscle runny nose, dry cough, sore throat, dry dry throat, red fluid, white or dry and and 6 one with of the in the and the other in the a a The course of treatment is days. a a The course of treatment is days. a 3 a for and 3 time. The the of and The of is the for 30 in a Severe cases (1) and syndrome Clinical fever, cough, or blood in shortness of fatigue, and in the of poor and short The is the is and the is and 6 3 5 one or with the in the or nasal it with 2 a 2 a the (2) of and syndrome Clinical fever, shortness of and or rash, or or in the The is with or no The is and or large and 30 30 30 30 6 6 and other with the in the or with can be to or can be in to clinical can be in with for and and for and the for 30 minutes in a Critically ill cases and syndrome Clinical or or dry and large without with or For patients with or of For patients with of and of while and muscle with can be to or can be in to clinical can be in with of for severe and cases The of the of from a small and the to the of the The is as infection or mild bacterial or or fever with of of and of inflammatory response syndrome multiple organ of and of of with of or of for the for and the for 30 a period (1) and spleen syndrome Clinical shortness of fatigue, and The is and 30 6 6 with of of the in the and the other in the (2) of and syndrome Clinical fatigue, shortness of dry poor low or no fever, dry cough, dry or 6 6 6 with of of the in the and the other in the for and the for and the for 30 a of minutes a treatment for children The syndrome characteristics and of children are the as those of The treatment is the treatment with of the clinical symptoms and the characteristics of can to to syndrome be to early of patients with COVID-19, and early and for respiratory and and be to and as as to the the of and In critically ill of of and of blood be Critically ill patients have of respiratory blood and as well as and 4 be and all be and patients change to of prone and and is in with is for and and as well as in patients with be for patients and and after for The can be the of N and of 2 2019-nCoV nucleic acid tests of mild are with a of or results of 2019-nCoV nucleic acid tests are with a of (1) to normal for more than 3 (2) respiratory (3) shows in acute The of N and of 2 2019-nCoV nucleic acid tests are with a of or results of 2019-nCoV nucleic acid tests are with a of Those who the can be after It is to 7 days of after from the in a with good reduce contact with and to and for are to the for the of by the 2019-nCoV by the Health of infection in the of the for the and of 2019-nCoV Infection in Health by the Health COVID-19 COVID-19 can reduce the of and severe disease and Those for vaccination all have the Those for the COVID-19 the in time. General are to good and a moderate and to fatigue. Health be and and or and or more are be well Everyone through and a fever respiratory symptoms occur. Those who have to or have an with or cases have nucleic acid test of The General of Health The General of of and The through in and the are the of the

Topics & Concepts