Severe Acute Respiratory Syndrome in Children

　　1. Etiology

　　Human coronavirus can cause respiratory and gastrointestinal diseases, among which human respiratory coronaviruses are one of the main pathogens causing colds, which can cause nasal congestion, runny nose, sore throat, and cough, and can also cause lower respiratory tract infections; human intestinal coronaviruses cause diarrhea; colds and diarrhea caused by coronaviruses are self-limiting. Coronaviruses mainly infect the respiratory tract, a few infect the intestines, and an extremely few have neurological symptoms. Therefore, respiratory secretions are the main transmission route, and they can also be transmitted through fecal-oral route and direct contact.

　　Second, pathogenesis

　　The SARS virus is the main pathogen causing this SARS. Currently, the characteristics of the SARS virus include high infectivity, strong pathogenicity, and it is a new type of coronavirus or a highly variant strain. The novel coronavirus may be transmitted through the following routes:

　　1, Infected through the eyes, nose, and mouth.

　　2, Close contact with patients without taking appropriate protective measures.

　　3, Direct contact with the secretions of patients or contaminated objects.

　　4, It may be transmitted through the air and other unclear routes. This virus is a new pathogen, and extensive research is needed in the classification, structure and function, pathogenicity, etiological diagnosis, epidemiological characteristics, and prevention and treatment of the virus.

　　Respiratory distress, circulatory failure, multiple organ dysfunction, shock, etc.

　　It may be accompanied by muscle tremors, etc. Respiratory failure caused by pulmonary disease can lead to cerebral edema and central respiratory failure. Heart rate can increase, and blood pressure may rise at the beginning of hypoxia, followed by a decrease. There may be intestinal paralysis, gastrointestinal ulcers, bleeding, and liver function damage. Compensation for respiratory acidosis, severe cases may have oliguria or anuria, even acute renal failure.

　　1, Age, gender, and epidemic history

　　Age 3 months to 13 years, most common in children over 3 years old, with no obvious gender difference in onset, and generally with a clear history of SARS contact.

　　2, Clinical symptoms and signs

　　Similar to adults, it has an acute onset, mainly manifested as fever and cough, with high fever peaks, axillary temperature often above 39℃, and an average duration of fever exceeding one week. It may be irregular fever, persistent fever, or remittent fever, but irregular fever is more common, which may be related to the irregular fever pattern in children due to the use of antipyretic drugs. Most children have coughs at the same time as fever, while a few children start to have coughs after several days of fever. Coughs are mostly productive coughs, while a few are dry coughs. Also, there are a small number of children who do not have coughs throughout the entire course of the disease. Most children do not have symptoms such as sore throat, nasal congestion, or runny nose, which are typical of upper respiratory tract viral infections. In addition to a few older children who complain of chest pain and headache, most do not have muscle aches, chills, headache, chest pain, and other symptoms. Unlike adults, positive signs are mainly manifested in the respiratory system. Most children have rales in the lungs, which can appear in the early or middle stage of the disease, mostly fine moist rales. The location of the rales is often consistent with the lung consolidation shown on the chest X-ray, which can be bilateral or unilateral and disappear as the disease improves. A few children may never have rales, and pathological respiratory sounds such as weakened breath sounds or tubular breath sounds may appear.

　　First, general preventive measures

　　Preventive measures against atypical pneumonia should be taken from five aspects to avoid infection:

　　1. Keep the air circulation in living and working environments;

　　2. Air can be disinfected by fumigation with edible vinegar acid;

　　3. Wash hands frequently;

　　4. Those who come into contact with patients must wear masks and pay attention to hand hygiene and disinfection;

　　5. Pay attention to keeping warm and preventing cold according to weather changes, participate in more exercise, enhance the body's ability to resist diseases, and prevent the occurrence of diseases.

　　(1) Air disinfection: Open the window for 10 to 30 minutes each time to allow air circulation and expel bacteria outside. If conditions permit, some air disinfectants approved by the health administration department can also be used for spraying or fumigation disinfection according to their instructions.

　　(2) Floor disinfection: Perform wet sweeping to prevent dust from flying and carrying bacteria into the air. At the same time, attention should be paid to keeping the ground dry.

　　(3) Disinfection of objects: Tables, chairs, thermos bottles, handles, switches, floors, toilets, bathtubs, etc. can be sprayed or wiped with 500mg/L effective chlorine disinfectant. For faucets, toilet door handles, and other moist places where bacteria are prone to adhere and reproduce, emphasis should be placed on disinfection.

　　(4) Disinfection of tableware: Boil with leftover food for 10 to 20 minutes. Tableware can be disinfected with 500mg/L effective chlorine, or soaked in 0.5% peracetic acid for 0.5 to 1 hour. When disinfecting tableware, it should be fully immersed in water, and the disinfection time starts from the boiling time.

　　(5) Hand disinfection: Wash hands frequently with running water and soap, and it is best to use 250 to 1000mg/L 1210 disinfectant or 250 to 1000mg/L effective iodine iodophor, or an approved hand sanitizer, before meals, after defecation, or after contact with contaminated items.

　　(6) Disinfection of clothing, towels, etc.: Cotton fabrics and diapers can be boiled for 10 to 20 minutes for disinfection, or soaked in 0.5% peracetic acid for 0.5 to 1 hour for disinfection. For some synthetic fabrics, silk, etc., only chemical immersion disinfection methods can be used.

　　Second, preventive measures in traditional Chinese medicine

　　Herbal medicine for general healthy individuals: Prescription one: 20g of fresh rhizome of rehmannia, 15g of lonicera, 15g of forsythia, 10g of cicada shell, 10g of caterpillar, 6g of mint, 5g of raw licorice, decocted as tea, taken continuously for 7 to 10 days. Prescription two: 12g of atractylodes, 15g of white atractylodes, 15g of astragalus, 10g of apium, 12g of hoelen, 15g of sand root, 20g of lonicera, 12g of Notopterygium, decocted and taken twice a day, continuously for 7 to 10 days. Prescription three: 10g of Notopterygium, 10g of lonicera, 10g of forsythia, 10g of indigo leaf, 10g of su leaf, 10g of pueraria, 10g of atractylodes, 15g of taizi root, 10g of pelargonium, decocted and taken twice a day, continuously for 7 to 10 days. For healthy individuals who have had contact with atypical pneumonia cases or suspected cases, under the guidance of a doctor, the following herbal medicine prescriptions are taken: 15g of raw astragalus, 15g of lonicera, 10g of bupleurum, 10g of scutellaria, 15g of isatis root, 15g of Notopterygium, 10g of atractylodes, 15g of coix seed, 10g of hoelen, 10g of apium, 5g of raw licorice, decocted and taken twice a day, continuously for 10 to 14 days.

　　Three, the prevention and treatment management of this disease

　　The onset time of this disease is in winter and spring, which is also the peak period for respiratory infectious diseases. The epidemiological manifestations are mainly the transmission of respiratory droplets at close range and contact with secretions of patients. Therefore, in order to prevent the spread of infectious diseases, in addition to early diagnosis and isolation of patients, disinfection and isolation of patients' excreta, secretions, and the environment and items they contact with are also essential measures. It is necessary to establish isolation wards and specialized clinics for treating such patients. The special ward is located at one end of the ward, and the ward is divided into contaminated area, semi-contaminated area, clean area, and critical care room, etc. The facilities in each ward are the same as those in ordinary wards, but there are special isolation gowns, thermometers, blood pressure monitors, stethoscopes, and other utensils at the door. In addition, disinfectant is provided for medical staff to wash their hands and disinfect, and the tap is an electric induction switch. Suspected and confirmed cases should be admitted to different wards. The ward has good ventilation, and all visitors to the ward are required to wear 12-layer cotton gauze masks, hats, change into isolation gowns, isolation pants, disposable socks, and shoe covers. The entrance and exit of the ward are equipped with foot mats (soaked in chlorine disinfectant with an effective chlorine concentration of 2000mg/L, for disinfecting the soles of shoes when entering and leaving), and disinfectant is sprayed at irregular intervals to keep it moist. All inpatients should wear masks, and strict isolation and management are required, and they must not leave the ward. A strict visiting system is implemented, and原则上 no attendants are allowed, and visits are discouraged as much as possible. If the condition of the child is critical, visitors must wear masks, hats, isolation gowns, and shoe covers.

　　(1) Disinfection and isolation in the ward:

　　①Air disinfection: The ward should be disinfected regularly with air every 4 hours; ultraviolet radiation should be used, not less than 1 hour per time (for empty wards), and chlorine disinfectant fumigation and spray disinfection (dosage: effective chlorine 20～30ml/m3, 1500mg/L chlorine disinfectant, effective for 30 minutes). The ward should have sufficient time to open windows and doors for ventilation every day to maintain air circulation.

　　②Disinfection of floors and surfaces: The floor should be mopped twice a day with chlorine disinfectant (effective chlorine 1500mg/2000ml) for 24-hour cleaning. In case of contamination, the floor should be mopped at any time. Tables, chairs, bedside cabinets, door handles, medical record folders, and other items should be wiped with chlorine disinfectant. The laboratory reports and medical records of each patient in the special ward should be disinfected with an ozone generator for 30min to 1 hour before being sent to the hospital's medical record room for filing.

　　③Disinfection of items used by patients: A. Items used by patients should be disinfected with 500～2500mg/L effective disinfectant solution before being poured into the patient's toilet. B. Used bedding should be soaked in 1000mg/L effective chlorine disinfectant for 30 minutes before cleaning. Domestic waste should be contained in double-layered garbage bags and disposed of effectively in a timely manner. Items after patients are discharged or die must be disinfected at the end of use.

　　(2) Personal protection for medical staff: The self-protection measures for medical staff must be strict and meticulous. In addition to providing effective protective equipment, measures to continuously improve the protection of medical staff should also be implemented. Drink cooling and detoxifying traditional Chinese medicine every day, and take antiviral drugs for prevention and gargle. Specific measures:

　　① When medical staff enter the ward for diagnosis and treatment, they must wear 12-layer cotton gauze masks and N95 masks, with wearing time not exceeding 4 hours, and replace them immediately if they become damp or contaminated. When performing close-range operations, protective goggles should be worn.

　　② Those entering the ward must wear three-layer cotton isolation gowns, two-layer cotton isolation pants, and a work hat.

　　③ Medical staff must disinfect and clean their hands immediately after each contact with patients, or use rapid hand disinfectant.

　　④ Change work clothes every day, and replace them immediately if they are soiled.

　　⑤ After medical staff contact patients and before going off duty, they can gargle with chlorhexidine gluconate mouthwash or compound chlorhexidine mouthwash. Before going off duty, carefully clean yourself (wash hands, face, and clean the nasal cavity), take a bath and change clothes before leaving the ward.

　　⑥ Pay attention to reasonably arrange the rest time of medical staff during work to avoid overwork. Medical staff should strengthen nutrition, enhance physical fitness, and improve the ability to resist diseases. The human resources arrangement for medical staff working in isolation wards should be twice as much as that in ordinary wards.

　　Clinical routine laboratory tests
　　(1) Routine blood tests: Should be done every 1-2 days, or once a day if necessary, and the interval can be appropriately extended during the recovery period. The dynamic changes of routine blood tests are one of the characteristics of the disease and an important diagnostic basis. In typical cases, peripheral blood leukocytes show progressive decline during the progression of the disease, and there is often a decrease in lymphocyte count.
　　(2) Detection of coronavirus antigen in throat swabs and blood coronavirus antigen: Establishing RT-PCR detection of coronavirus antigen. Its clinical diagnostic value needs to be verified by more clinical practice. Pay attention to collect specimens during the early stage of fever and the viralemia period. Throat swab virus isolation to check for respiratory syncytial virus, type A influenza virus, type B influenza virus, enterovirus,拉萨热virus, hantavirus, adenovirus, throat swab mycoplasma PCR, and blood test for mycoplasma antibody (MP-IgM), chlamydia antibody (CP-IgM) are necessary to exclude other pathogens causing pneumonia.
　　(3) Sputum bacterial culture and drug susceptibility testing, blood culture for pathogenic球菌 with drug susceptibility testing: Helps to exclude or diagnose bacterial infection.
　　(4) For diarrhea patients: Additional tests for coronavirus, rotavirus, and adenovirus antigens in feces should be performed.
　　(5) PPD skin test: Helps to exclude or diagnose pulmonary tuberculosis infection.
　　(6) Blood sedimentation rate, C-reactive protein, cold agglutination test; for those with fever exceeding 1 week, add Widal test, Weil-Felix test, anti-hemolysin streptococcus 'O', and rheumatoid factor (RF) to help with differential diagnosis.
　　(7) Immune function: Checking T cell function and immunoglobulin levels helps to understand the changes in the child's immune function.
　　(8)心、肝、肾功能相关检查：起病初期查脏器功能指标并定期复查，包括谷丙转氨酶、谷草转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶、总蛋白、白蛋白、球蛋白、白蛋白/球蛋白比值、总胆红素、间接胆红素、直接胆红素、葡萄糖、尿素氮、尿酸、肌酐、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶、淀粉酶。
　　(8) Cardiac, liver, and renal function related examinations: Check organ function indicators in the early stage of onset and review regularly, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, total protein, albumin, globulin, albumin/globulin ratio, total bilirubin, indirect bilirubin, direct bilirubin, glucose, urea nitrogen, uric acid, creatinine, creatine kinase isoenzyme (CK-MB), lactate dehydrogenase, amylase.

　　Dietary recommendations and禁忌 for patients with severe acute respiratory syndrome in children

　　1. Follow the doctor's orders to provide high-concentration oxygen inhalation or use end-expiratory positive pressure breathing (PEEP), and adjust the oxygen concentration according to the changes in arterial blood gas analysis values. Use diuretics as prescribed to reduce interstitial and alveolar pulmonary edema.

　　2. Assist with turning over and patting the back, every 2 hours, to promote the excretion of secretions. Keep the bedsheet dry, flat, and clean. If necessary, provide an air-filled bed or place an air cushion at bony prominences.

　　4. Strengthen nutrition, provide high-protein, high-vitamin diet.

　　I. Treatment

　　1. Treatment plan

　　The treatment plan for severe respiratory syndrome in children in May 2003 (trial) is as follows:

　　(1) General treatment: Ventilation, rest, drinking plenty of water, and strengthening nutrition.

　　(2) High fever: For those with fever above 38.5℃, with significant general malaise, physical cooling measures can be used or antipyretic analgesics can be administered, such as ibuprofen (half dose for those with fever below 38.5℃). Aspirin should be avoided.

　　(3) Cough and expectoration.

　　(4) Antiviral: Ribavirin 10-15mg/(kg·d) can be used, intravenous infusion or oral administration for 7-10 days.

　　(5) Antibiotics: Macrolide antibiotics such as azithromycin 10mg/(kg·d), can be intravenously infused for 5 days, then stop for 3 days, as one course of treatment; according to the condition, another 1-2 courses of treatment can be considered. If other bacterial infections occur, first-generation or third-generation cephalosporins can be selected according to the situation.

　　(6) Immune regulatory drugs: Human plasma gamma globulin 400mg/(kg·d), intravenous infusion for 3-5 days. For critically ill children, plasma can be considered, 10-20ml/(kg·d), for 3-5 days consecutively.

　　(7) Adrenal cortical hormones: After strictly excluding contraindications, critically ill children (with high fever, severe cough, dyspnea, significant changes in chest X-ray films and rapid progression, or with damage to other organs) can be selected under the premise of enhanced supportive treatment. Such as methylprednisolone 2mg/(kg·d), for 2-3 days; or dexamethasone 0.1-0.2mg/(kg·d).

　　(8) Other: Nutritional myocardial drugs, such as energy mixture and vitamin C; liver protection drugs, etc.

　　2. Pay attention to issues

　　(1) Blocking the cascade reaction: The key to the pathophysiological process of SARS is the continuous amplification of systemic inflammatory response syndrome (SIRS), causing a cascade reaction (cascade), leading to

　　(2) Respiratory care: CT and autopsies of SARS patients indicate that the lung fibrosis in SARS patients is not interstitial fibrosis, but obstruction of the trachea caused by fibrous mucus exudation due to lung inflammation and hypersensitivity reactions. Adrenal cortical hormones can slightly alleviate the obstruction, but the significance is not great. The key is early strong respiratory care and supportive treatment. Excessive administration of adrenal cortical hormones may worsen the body's stress state and also cause serious secondary infections, aggravating the condition. Moreover, early use of adrenal cortical hormones has no preventive effect on multiple organ damage, so it is not advisable to use hormones routinely according to pediatric cases. The indications for the use of adrenal cortical hormones are: ① Severe toxic symptoms; ② Patients meeting the criteria for severe cases. The specific dose and application time should be adjusted according to the condition. If other treatment measures are effective, try not to use corticosteroids. Avoid forceful and violent coughing during the period of lung consolidation. Generally, children should be encouraged to cough, and attention should be paid to turning over and patting the back to try to promote the excretion of respiratory secretions.

　　(3) Supportive treatment: Try to ensure that each child has a separate ward to ensure their rest. Appropriately supplement fluids and vitamins, and encourage children to eat more fruits and protein-rich foods. If the child's nutritional status is poor, intravenous nutritional support therapy should be given, especially for infants and young children who have difficulty with feeding. Pay special attention to intravenous nutritional support therapy, and appropriately supplement vitamins, amino acids, and fat emulsion. The use of fat emulsion should pay attention to the child's liver function. Especially for small infants, as some children may have concurrent liver damage. Children with cough and sputum should be given promethazine (Phenergan) and other cough suppressants and expectorants.

　　(4) Oxygen therapy: Regularly review chest X-rays and kidney, liver, and heart function. Monitor transcutaneous blood oxygen saturation daily. Emphasize early, full, and adequate oxygen supply. Most patients may be in the progressive stage within 14 days after onset, especially in the second week of the disease course. Even if the symptoms of fever and cough in children are not severe, lung lesions can still continue to progress and there is a possibility of sudden changes. Generally, nasal cannula oxygen therapy (1L) is given, and for small infants, head罩 oxygen therapy (3-5L) is given to ensure oxygen saturation > 97%. For those with significant shortness of breath and mild hypoxemia, continuous nasal cannula oxygen inhalation should be given as soon as possible. Oxygen therapy should pay attention to the child's compliance, and intermittent oxygen therapy can be given according to the condition. The duration of intermittent oxygen therapy should last until the recovery period of the disease.

　　(5) Antipyretic and symptomatic treatment: For those with fever over 38.5°C, antipyretic and analgesic drugs such as ibuprofen can be used. Aspirin should not be used in children, as it may cause Reye's syndrome. For patients with high fever, physical cooling measures such as ice packs and alcohol rubs can be applied. For patients with organ damage such as heart, liver, and kidney, appropriate treatment should be given. For children with refractory high fever, rapid progression of lung lesions, respiratory distress, hypoxemia, and those with a tendency to develop shock, ARDS, or MODS, it is necessary to promptly administer high-dose intravenous injection of human blood immunoglobulin (IVIG), 400mg/(kg·d), for 3 consecutive days. Most children with high fever will see a decrease in body temperature on the second day after the administration of IVIG, a few on the third day, and some on the fourth day. Generally, children will see their body temperature return to normal within 4 days after the administration of IVIG. The significant therapeutic effect of IVIG may be related to the following factors. ①IVIG has phagocytic and opsonic effects, which can enhance the function of phagocytes. ②IVIG has specific antibody effects. Due to the previous neutralizing antibody positivity rate of 30% to 60% in the Chinese population against coronaviruses, if the pathogen in this case is a variant strain of coronavirus, IVIG will still contain antibodies against the common antigenic determinant of coronaviruses; ③IVIG has the effect of blocking cytokines and interrupting the cytokine cascade.

　　II. Prognosis

　　From the current understanding of the transmission process of atypical pneumonia, the infectivity of patients with atypical pneumonia is mainly in the acute phase (early stage of onset), especially at the very beginning of the illness. After patients with atypical pneumonia are isolated and treatment measures such as antiviral therapy and enhancing the body's immune response are taken, the body begins to recognize the virus and produces specific immune responses against SARS to resist and neutralize the virus. As the disease recovers, the SARS virus is gradually cleared by the body, and its infectivity also disappears. Severe cases are prone to complications, which can lead to death. With positive and correct treatment, the prognosis of children with SARS is good, and there have been no reported deaths.