Сontents

This review is specialized for:

  • Medical organizations top-management
  • General practitioners
  • Ambulance crew medicals
  • Infectious diseases physicians
  • Resuscitators in infectious hospitals
  • Obstetricians and gynecologists
  • Pediatricians
  • Other medical staff providing care for patients with COVID-19

VIRUS SPREAD

  • Infection occurs through the respiratory tract, stomach, and intestines. Probably through the eye mucosa
  • The infection lives in a sick person or a person in the incubation period. Adult incubation period: from 2 to 14 days (mostly within 5-7 days). In children: from 2 to 10 days, usually 2 days;
  • Routes of transmission:
  1. Airborne: talking, sneezing, coughing.
  2. Air-dust: infected air, infectious aerosols.
  3. Contact: surfaces and objects contaminated with the virus. At the average room temperature, SARS-CoV-2 is viable on objects for 3 days.
  4. Fecal-oral route.

PREVENTION

Non-specific prevention: preventing the infection spread

  • Patients and persons with the suspected illness must be isolated
  • Be sure to use medical masks for patients around the clock. It is twice as reduces the risk for others
  • Hygiene:
  1. Wash your hands with soap for 20 seconds.
  2. Use disposable wipes when sneezing and coughing.
  3. Touch the face only with clean wipes or washed hands.
  • Use disposable medical masks. Change it every 2 hours
  • It is mandatory to use personal protective equipment (PPE)
  • Irrigate the nasal mucosa with an isotonic solution of sodium chloride to reduce the number of viruses and bacteria
  • Contact the medical organization at the onset of symptoms of acute respiratory viral infection (ARVI)
  • Constantly ventilate rooms and wards to reduce the virus concentration;
  • Do not use air conditioners (split A/C’s). It’s increasing the risk of infection by blocking natural ventilation
  • Be sure to decontaminate medical waste, including human biological secretions. They are extremely epidemiologically dangerous. Physical methods of disinfection: thermal, microwave, radiation. Medical organizations are ought to have specialized equipment installed

Drug therapy

For adults: intranasal recombinant interferon-alpha 5 times per day for 5 days long. Single-dose is 3000UI.

For pregnant women:  intranasally recombinant interferon-alpha 2b (IFN-α2b) only.

Chemoprophylaxis: use of hydroxychloroquine. If unavailable – mefloquine.

PROTECTION

Personal protection

  1. Medical cap
  2. Anti-Plague (surgical) dressing gown, type 1 infectious disease overalls
  3. FFP2 Respirator or equivalent
  4. Two pairs of medical gloves
  5. Safety glasses and protective visor
  6. Shoe Covers

How to use a respirator

  • Respirator usage during the working day should be interrupted only for hygiene reasons;
  • Remove the respirator with gloves and elastic bands. Remove the lower elastic band first, then the upper one. Do not touch the respiratory surface
  • If there is a shortage of respirators, limited reuse is possible
  • Terms for respirator repeated use:
  1. The respirator is not physically damaged.
  2. The respirator provides a tight fit to the face.
  3. The respirator does not create excessive breathing resistance due to high humidity.
  4. The respirator has no visible signs of contamination with body fluids.
  5. The duration and frequency of reusing are determined by conditions 1 – 4.
  • When re-using, mark the respirator with your initials, disinfect it with ultraviolet bactericidal irradiation (minimum of 30 minutes), let it dry completely, and store it in a paper bag or napkin
  • For repeated use, wear a surgical mask over the respirator. Change the mask after any contacts with infected patients
  • Used respirators should not be washed, mechanically cleaned, treated with disinfectants, decontaminated with high temperatures or steam
  • It is forbidden to transfer the used respirator to another person

How to protect your workers in offices:

  • Differentiate the flow of potentially infected and uninfected patients
  • Shift the stuff regularly
  • Make distant zones in diagnostic rooms to limit staff contact with patients;
  • Clean rooms and wards, sterilize equipment and furniture
  • During surgical procedures, turn on ventilation as much as possible. Surgeries air will be highly diluted and should not be considered as a possible infectious agent
  • Use disinfectants and bactericidal irradiators in the emergency room to disinfect air and surfaces

Ambulance brigade protection

  • The ambulance staff should wear PPE immediately before departure. Change t PPE after each patient. Used PPE should be placed in a sanitizing solution, then discarded in a class B medical waste container
  • Disinfect the air in the car interior with bactericidal irradiators and (or) other devices for disinfecting the air and (or) surfaces during patient loading and evacuating
  • If the passenger compartment is contaminated with the patient’s biological material, immediately decontaminate the areas of contamination
  • It is forbidden to transport more than one patient in one car
  • It is forbidden to transport persons who have had contact with the patient in the same car
  • After the patient evacuation, it is necessary for the brigade to disinfect shoes and hands, and treat the exposed parts of the body with a skin antiseptic. Change into a spare set of clothes
  • Disinfect all surfaces in the vehicle interior and medical devices after patient evacuation. Clean the surface with water after disinfection, wipe dry, and ventilate until the smell disappears
  • Finally, disinfect the air and interior of the car with bactericidal irradiators for at least 20 minutes

DISEASE PROCESS

  • In 80% of patients, the disease occurs in a mild form of ARVI
  • Severe forms develop in patients at risk: cardiovascular diseases, diabetes, age 60+
  • Children have a lighter course. The viral pneumonia is not typical, the symptoms are less pronounced and deaths are rare
  • Changes in the sense of smell at an early disease stage may indicate brain damage

SYMPTOMS VARIETY OF COVID-19:

  • ARVI: only the upper respiratory tract is affected
  • Bilateral pneumonia
  • Pneumonia without respiratory failure
  • Pneumonia with acute respiratory failure (ARF)
  • Acute respiratory distress syndrome (ARDS)
  • Hypoxemia, decreased blood oxygen saturation (SpO2) less than 88 %
  • Sepsis
  • Septic (infectious-toxic) shock
  • Thromboses
  • Thromboembolisms

SYMPTOMATOLOGY

COVID-19 is characterized by SARS symptoms.

  • Increased body temperature, high fever
  • Cough dry or with a small amount of sputum
  • Runny nose
  • Sore throat
  • Hemoptysis
  • Dyspnea
  • Palpitations and shortness of breath
  • Heart palpitation
  • Feeling of congestion in the chest
  • Fatigability
  • Weakness
  • Myalgia
  • Signs of conjunctivitis
  • Anosmia
  • Hyposmia
  • Reduction of taste
  • Headache
  • Disturbance and confusion
  • Nausea
  • Diarrhea
  • Vomiting

DIAGNOSTICS

Physical examination

  • Auscultation and lungs percussion
  • Lymph nodes palpation
  • Abdominal organs examination to determine the liver and spleen size
  • Thermometry
  • Level of consciousness assessment
  • Measurement of heart rate, blood pressure, and respiratory rate
  • Pulse oximetry with SpO2 measurement to detect respiratory failure and assess the severity of hypoxemia

Laboratory diagnostics

  • Detection of SARS-CoV-2 RNA using nucleic acid amplification methods. The material is taken from the nasopharynx and/or oropharynx. Nasopharyngeal and oropharyngeal smears should be placed in the same tube in order to increase the virus concentration. Storing temperature should be +2° +8° C. The storage time for samples should not exceed 5 days. It may store longer at -20° C or -70°C
  • Detection of C-reactive protein (CRP) level in blood serum. The level of CRP correlates with the prognosis for pneumonia

Instrumental diagnostics

  • Radiography (X-Ray) is not suitable for early diagnosis due to low sensitivity;
  • Computed tomography (CT scan) has the maximum sensitivity to detect specific COVID-19 pneumonia in lungs
  • The volume of lung damage in X-Ray and CT scan may not have a direct correlation with the clinical severity of the disease. The detected signs are not specific and do not allow to establish an etiological diagnosis
  • Ultrasound lung examination may be used as an additional method of visualization. The treatment effectiveness depends on the doctor’s experience and qualifications. Lungs ultrasound does not replace the use of X-Ray and CT scan. But it can speed up the diagnosis of pneumonia for certain groups of patients, such as pregnant women and newborns if there is a large patience flow

TREATMENT

General recommendations

  • There is no evidence of the effectiveness or ineffectiveness of COVID-19 etiotropic treatment
  • Before confirming the etiological diagnosis, use treatment regimens for seasonal ARVI: intranasally interferon-alpha, interferon inducers, antiviral drugs with a wide range of activity (ex. Umifenovir)
  • In the initial stage, interferon-alpha suppresses viral replication in the respiratory tract, reduces viral load, reduces symptoms, and reduces the disease duration. Intranasal apply of Recombinant IFN-α2b has an immunomodulatory, anti-inflammatory and antiviral effects
  • Conduct pre-emptive anti-inflammatory therapy (before appearing of pneumonia, ARDS and sepsis)
  • Conduct supportive pathogenetic and symptomatic therapy
  • Perform infusion therapy against the background of forced diuresis to prevent brain edema and pulmonary edema. Furosemide 1% 2-4 ml intramuscularly or intravenously
  • Use enterosorbents for severe intoxication, abdominal discomfort, nausea and vomiting
  • Ensure a sufficient water intake amount. The daily requirement should be calculated according to the fever level, shortness of breath, diarrhea, and vomiting. The average amount of liquid: 1.5-2 liters per day or more, if there are no contraindications for somatic pathology
  • Patients in severe condition should be given antibacterial therapy and perform infusion therapy (if indicated). The fluid should be injected at a low speed to keep it safe for the patient. It is recommended to perform a probe feeding with standard and semi-elemental mixtures to reduce the volume of infusion therapy. Feeding should be frequent and fractional to avoid stomach overflow and lungs volume reducing
  • For severe ARDS, low-turnover lungs, and acute pulmonary heart disease (or its high risk), immediately perform extracorporeal membrane oxygenation to reduce a chance of death
  • Patients in severe condition should be treated with oxygen therapy while lying on their stomachs at least 2 times a day, for a total of 12-16 hours. The in-time prone position improves oxygenation, helps avoid intubation, and reduces lethality. 

Prone position manual: put the patient on the stomach, place the rollers under the chest and pelvis, so that the stomach does not exert excessive pressure on the diaphragm and avoid face bedsores

Prone position contraindications: consciousness diseases (depression or agitation); hypotension; recent surgery on the abdominal or thoracic cavities; massive bleeding; spinal cord injuries; rhythm disturbances that may require defibrillation and/or heart massage

  • Do not delay tracheal intubation and ventilation if ARDS and personal indications are active. Respiratory failure can occur very quickly. Delaying tracheal intubation and lungs ventilation could worsen the prognosis
  • Extend the respiratory support for up to 14 days or more if ARDS is confirmed. With positive dynamics of lungs, oxygenating function the deterioration of ARDS is possible. The average duration of ventilation is 14-21 days

Etiotropic treatment

  • Children’s antiviral therapy. In the case of mild or moderate disease use interferon-alpha. Severe form: intravenous immunoglobulins, protease inhibitors (lopinavir + ritonavir)
  • Combinations of drugs: chloroquine, hydroxychloroquine, lopinavir + ritonavir, azithromycin (in combination with hydroxychloroquine) and drugs based on interferons
  • Local immunomodulatory, anti-inflammatory and antiviral therapy: recombinant interferon-alfa, 3 drops per nostril (3000 IU) 5 times a day for 5 days
  • Monotherapy with lopinavir + ritonavir does not reduce the time of hospitalization and does not demonstrate greater effectiveness than standard symptomatic therapy. Monotherapy is recommended only for contraindications to chloroquine, hydroxychloroquine, and mefloquine

Pathogenetic treatment

  • Treatment of microthrombosis and normalization of microcirculation in the lungs with low-molecular-weight heparins (NMH) radically increase the survival rate of patients. In prophylactic doses are shown TO ALL hospitalized patients. In the absence of HMG, use unfractionated heparin (NPH). For deep vein thrombosis, pulmonary embolism, use therapeutic doses of NMG/NPG. Increased prothrombin time and activated partial thromboplastin time do not belong to the contraindications of NMG/NPG
  • Contraindications for NMG/NPH:
  1. Ongoing bleeding.
  2. The level of platelets in the blood is below 25*109/l.
  3. Severe renal failure (for NMG)
  • Pre-emptive anti-inflammatory therapy: tocilizumab and sarilumabum. When ARDS is confirmed, an excessive response of the immune system occurs with quickly released cytokines (cytokines storm) which both increase the chance of death
  • Signs of a cytokine storm:
  1. Interleukin-6 (IL-6) > 40 PG / ml.
  2. CRP > 60 mg / l or a three-fold increase in the level of CRP
  3. Blood ferritin > 1000 ng/ml.
  4. Compacted lung tissue volume is 50-75%
  5. Reducing SpO2
  6. Fever >38°C for 5 days
  7. White blood Cells < 3,0-3,5*109 /l,
  8. Lymphocytes < 1*109 /l and / or < 15%
  • Contraindications of IL-6 receptor inhibitors:
  1. Sepsis by pathogens other than COVID-19
  2. Hepatitis B
  3. Immunosuppressive therapy for organ transplantation
  4. Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) is more than 5 times the upper limit of a normal level
  5. Neutropenia < 0,5*109/l
  6. Thrombocytopenia < 50*109/l
  • In tuberculosis, the use of IL-6 receptor inhibitors should be approved by a phthisiologist
  • Backup therapy for hyper inflammation (for life indications): corticosteroids, baricitinib

Symptomatic treatment

  • Relief of fever if the temperature is above 38.0-38.5° C.  Use paracetamol 500-1000 mg up to 4 times a day, but no more than 4g per day
  • In the case of rhinitis, pharyngitis, rhinopharyngitis. Locally: salt isotonic and hypertonic solutions. Additionally: moisturizing/elimination drugs, nasal decongestants, antiseptic solutions
  • To cure bronchitis use mucoactive drugs: acetylcysteine, ambroxol and carbocysteine, inhale of salbutamol and fenoterol

Antibacterial therapy

  • The choice and use of antibiotics should be based on the severity of the patient’s condition and the results of microbiological diagnostics
  • For patients in serious condition it is necessary to conduct a combined therapy:
  1. Protected aminopenicillins: amoxicillin/clavulanate, amoxicillin/sulbactam.
  2. third-generation Cephalosporins (Ceftriaxone, Cefotaxime of ceftaroline fosamil) intravenously in combination with azithromycin or clarithromycin intravenously.
  3. third-generation Cephalosporins (Ceftriaxone, cefotaxime) intravenously in combination with a respiratory fluoroquinolone (levofloxacin, moxifloxacin) intravenously.
  4. when using fluoroquinolones with group 4-aminoquinolones (chloroquine, hydroxychloroquine, mefloquine), there is a risk of cardiotoxic effect.

Therapy of patients with arterial hypertension

  • Additional treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers
  • There is no evidence that these drugs increase the risk of death since ACE 2 is a functional receptor for SARS-CoV-2
  • There is indirect data on the possible protective effect of these drugs in COVID-19

PATIENTS MONITORING INSTRUCTION

  • Body temperature measure: daily, at least twice a day. Check if temperature increase after being stabilized for a day or more
  • NPV measure: Daily. If NPV on outpatient care is more than 22 per minute, the patient should be hospitalized
  • SpO2 measure: daily. When the level is ≤ 93%
  • CT and X-Ray scan: at least once in 7 days
  • ECG to examine possible arrhythmia, acute coronary syndrome, prolongation of the QT interval.
  • White blood cells, neutrophils, lymphocytes and  platelets
  • ALT, AST, CRP, ferritin, troponin
  • D-dimer
  • Prothrombin time
  • Fibrinogen
  • IL-6.
  • T-lymphocytes, B-lymphocytes.

DIRECTIONS FOR PREGNANT AND NEWBORNS HYGIENE 

  • Bleeding prevention at any term of pregnancy
  • Recombinant interferon beta-1b and antimalarial drugs are contraindicated for pregnant women. They should only be used for vital reasons
  • Termination of pregnancy and parturition during the disease increases the risk of maternal mortality and causes many complications
  • If lung ventilation causes hypoxia, respiratory failure, alveolar pulmonary edema, and refractory septic shock, perform a cesarean section for vital indications. Prevention of coagulopathic and hypotonic obstetric bleeding is mandatory
  • For spontaneous labor in the midst of pneumonia, it is preferable to conduct labor through the natural birth canal under monitoring
  • Recommendations for a newborn:
  1. Delayed clamping of the umbilical cord is not recommended.
  2. It is not recommended to contact the mother-child relationship.
  3. Do not put your child against the chest.
  4. Evacuate a newborn out of the delivery room as quickly as possible.
  5. Vaccination and neonatal screening should be postponed until COVID-negative status is established.
  6. Provide individual diagnosis tools, treatment methods, and care for every child.

TERMS OF DISCHARGE

  • 2 negative tests for SARS-CoV-2 with an interval of at least one day.
  • Body temperature less than 37.2° C
  • DRR less than 2 norms
  • White blood cell level above 3.0 x 109/l
  • SpO2 over 96%

AUTOPSY

  • Should be performed as early as possible
  • Photo and video recording of all diagnostically significant morphological changes is highly important
  • Histological study of morphological changes in the main organs. Special attention is paid to the respiratory system
  • Differentiate diagnosis: COVID-19-underlying disease or other diseases, if COVID-19 is present
  • Microscopic examination:
  1. Proximal and distal trachea
  2. The сentral part of the lung with segmental bronchi, right and left bronchi of the first order
  3. Representative sections of  pulmonary parenchyma from the right and the left
  4. Liver
  5. Spleen
  6. Kidneys
  7. Heart
  8. The adrenal gland
  9. Pancreas
  10. The brain with a soft braincase
  11. Stomach
  12. Small intestine
  13. Large intestine
  14. Intra-Thoracic lymph node
  15. Other modified organs and tissues

EMERGENT, INPATIENT AND OUTPATIENT MEDICAL CARE RECOMMENDATIONS FOR CLINICS

  • To inform:
  1. Medical stuff about preventive measures, diagnosis, and treatment of COVID-19
  2. Citizens to raise awareness of the COVID-19 risks as well as preventive measures and timely treatment for SARS symptoms
  • To organize:
  1. An anti-epidemic measure when detecting suspicion of COVID-19
  2. Rooms and wards airing, air disinfection and use of PPE
  3. Control of the concentration of disinfectants
  4. A possibility of remote issuance of sick leaves, extracts, drugs, including house delivery and shipping
  5. A possibility of outpatient treatment at home for non-symptomatic or mild severity
  6. Hospitalization of patients with atypical SARS and pneumonia
  7. Admission of patients with suspected COVID-19 through the reception and examination boxes and further routing of patients in clinics
  8. Workspace without any possibility of meeting with colleagues who were in contact with COVID-19 patients
  9. SARS-CoV-2 testing of workers who are in contact with COVID-19 patients on
  10. Possible postponement of planned medical care
  • To provide:
  1. PPE.
  2. Items of emergency prevention for staff
  3. Equipment: pulse oximeters, ventilators, class b medical waste decontamination plants
  4. Test systems for COVID-19 diagnostics
  5. Supplies for testing procedures
  6. Monthly supply of disinfectants

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