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COVID-19 Update from China

The 2/19/2020  Chinese Health and Public Health Ministry Guideline on Novel Coronavirus Disease (COVID-19) Diagnosis and Treatment (Revision #6)

(Anlin Xu MD, translation for the  US Healthcare System/Hospitals/Clinics)

 

  1. Characteristics of Pathogen

 

The Novel Coronavirus (2019-nCoV) belongs to the family of beta Coronavirus family.  It has significant genetic differences from SARSr-CoV, and MERSr-CoV.  Current research indicates that it has 85% genetic similarity with bat-SL-CoVZ45, isolated from bats.  When cultured outside the human body, 2019-nCoV can be detected in human respiratory epithelial cell within 96 hours, and after 6 days in Vero E6 and Huh-7 cells.

 

The virus is sensitive to UV light and heat.  Heat for 56C for 30min, Diethyl Ether, 75% Ethanol, disinfectant with chloride, H2O2, and other chlorinated disinfectant can effectively deactivate virus.

 

  1. Characteristic of Infectibility

 

  1. Origin of Infection

Currently the main source of Infections are patients infected with the virus.  Patients without any clinical symptoms can also infect others.

  1. Route of Transmission

Droplet and close contact are the main route of transmission.  Within enclosed environment, long time exposure in high viral load situation, transmission through aerosol is possible.

 

  1. Susceptible population

The general population (a supplemental guideline from the front line hospitals says most patients infected are adults 30 years or older)

 

  1. Clinical Characteristics (of COIVD-19)

 

  1. Clinical Presentation

 

Incubation Period is 1-14 days, most 3-6 days.

 

Fever, dry cough, fatigue are the primary symptoms.  Some patients have nasal congestion, rhinorrhea, sore throat, and diarrhea.  Severe patients usually develop difficulty breathing and hypoxia 1 week after onset of symptoms.  Critical patients may develop rapid progression into ARDS, sepsis, uncorrectable metabolic abnormality, DIC, and multi-organ failure.  Notably, severe and critical patients can have low grade fever, or no fever at all.

 

Mild patients present with low grade fever, mild fatigue, etc., without any signs of pneumonia.

 

From current cases, majority of patients can recover well.  Minority of patients become critical.  Elderly patients and patients with baseline diseases have poor recovery.  Children generally have milder symptoms.  (a supplemental guideline from the frontline hospitals says that it appears male have more severe diseases than female, and have a higher mortality rate)

 

  1. Labs

 

In early stages of the disease, peripheral WBC number decreases, so is absolute lymphocytes.  (A supplemental guideline from the frontline hospitals also says that absolute lymphocyte/absolute neutrophil ratio seems to have some value in determining the severity of a patient’s disease, and help to indicate trend in a patient’s condition.  The lower the ratio, the more severe the patient is.)

 

Some patients have elevated liver enzymes, LDH, and Myoglobulin; most patients will have elevated CRP and ESR.  Severe patients have elevated D-Dimer, suppressed peripheral lymphocytes.  Severe and critical patients showed signs of elevated inflammatory mediators (cytokines).  Some critical patients have elevated troponin.

 

Virus can be detected through RC-PCR in patient’s nasopharyngeal swab, sputum, other lower airway secretions, blood, and feces.

 

To increase the sensitivity of detecting the virus, recommend to collect sputum, and lower respiratory secretion during intubation, and send for testing as soon as possible.

 

  1. Radiograph

 

Early stages usually present with small infiltrates and interstitial changes, more apparent in the peripheral of the lungs.  Later on, radiograph evidence can progress to bilateral ground glass appearance, and diffuse infiltrates.  Severe patients can develop solid changes in the lungs.  (A supplemental guideline from frontline hospitals indicated that some critical patients develop “white lungs”).  Pleural effusion is unusual.

 

  1. Diagnostic Criteria:

 

  1. Suspected cases

Clinical suspicion can be made by the combination of contact history with clinical presentation.

  1. close contact with known infected individual within 14 days, traveled from endemic cities and regions within 14 days, and patient is a member of a cluster appearance of infected individuals.
  2. Clinical presentation of fever and respiratory symptoms; or radiographic evidence that is consistent with 3(c); or in early stages of the disease with lower peripheral leukocytes and lymphocytes.

If a patient meets 1 criteria in i), and 2 criteria in ii); or all three criteria in ii), the patient is a highly suspected case.

 

  1. Confirmed cases

 

If a suspected case meets one of the criteria of 1) RT-PCR positive for 2019-nCoV, or 2) genetic sequence highly consistent with 2019-nCoV.

 

  1. Clinical Types

 

  1. Mild:

Mild clinical disease, no evidence of pneumonia on radiography.

 

  1. Moderate:

Fever, respiratory symptoms, and pneumonia on radiography.

 

  1. Severe:

Any one of the three below:

  1. Tachypnea, RR>30
  2. SatO2 <=93% on RA
  • PaO2/FiO2 <=300mHg
  1. Chest radiography (XR or CT) showed >50% progression within 24-48 hours.

 

  1. Critical:

Any of the three below:

  1. Respiratory failure, requiring mechanical ventilation
  2. Syncope
  • Other end organ damage requiring ICU care.

Need to rule other respiratory or systemic diseases that could mimic COVID19 (I am omitting that part.  We all know)

(….  Other things about reporting, I am skipping here because it’s only relevant to the Chinese CDC)

 

  1. Treatment

 

  1. Treatment locations: suspected cases should be insolation.  Confirmed cases can be treated in shared rooms (with other confirmed cases).  Critical cases should be treated in ICU.  (I believe this recommendation is given because of the critical shortage of all kinds of hospital beds in some of the cities located in the epicenter of the disease)

 

  1. Treatment for Mild to Moderate diseases:
  2. Rest, supportive care, supply sufficient nutrition and fluid. Pay close attention to electrolyte balance.  Close monitoring of vitals and SatO2.
  3. Monitor routine blood and urine labs, including CBC and diff, liver function, kidney function, CRP, coagulation, PaO2, and chest radiography. In indicated patients, can monitor inflammatory cytokines.
  • Ensure sufficient oxygen supply, with NC, face mask, or high flow O2 treatment.
  1. Some recommended anti-viral treatments to try (there is currently no proven anti-viral for this virus. The most promising one according to WHO officials is Remdisivir from Gilead):
    1. Alfa-interferon (5,000,000 U or similar dose, with 2ml sterile water, nebulized bid), can be given in combination with any treatment below.
    2. Kaletra (Lopinavir/ritonavir) 200mg/50mg 2 tab bid, for up to 10 days (monitor for GI side effect, such as nausea, vomiting, diarrhea, and elevated liver enzymes)
    3. Chloroquine Phosphate 500mg bid, for up to 10 days.
    4. (Gilead’s Remdisivir is currently under clinical study in China, so it’s not included in this guideline.)
  2. Avoid inappropriate usage of antibiotics.

 

  1. Treatment for Severe and Critical Diseases:

 

  1. Continue with treatment of Mild to Moderate diseases as above.
  2. Respiratory support:
    1. O2 through NC
    2. O2 through face mask or high flow O2 if patient is de-sating. If high flow O2 is not sufficient to alleviating symptoms or low Sat O2 within 1-2 hours, or patient is deteriorating, start intubation and mechanical ventilation.
  • Invasive Ventilation:
    1. Use pulmonary protective protocol (this part is too technical, so I am translating the paragraph verbatim): low volume (4-8ml/kg ideal body weight); and low pressure (plateau pressure <30cm H2O), to decrease ventilator related pulmonary trauma. Adjust for high altitude.  Majority patients have asynchrony with mechanical ventilation, recommend sedation and muscle relaxant (paralytics?) when indicated.
    2. In severe ARDS patients, recommend pulmonary re-ventilation, when allowed, should have 12hr/day prone position ventilation. If still deteriorate, consider ECMO as soon as indicated.
    3. Support micro circulation, use anti-coagulants as indicated.
    4. Recovering patient’s plasma transfusion (I don’t think it pertains in US. Even in China, it’s a very limited resource).
    5. Other treatment: for rapidly deteriorating pulmonary or cytokine storm patients, consider glucocorticoids 1-2mg/kg, but be judicious in using glucocorticoids as it can suppress the body’s immune system and slow the clearance of the virus.  Probiotics to prevent secondary infection through GI tract.  With cytokine storm patients, consider plasmapheresis.
    6. Patients usually have significant anxiety. Pay attention to patient’s psychological health.

 

(….  Then a section regarding Chinese herbal medicine, which doesn’t pertain to us.  We skipped)

 

  1. Standard on ending isolation and discharge:

The patient can be discharged if they satisfy all below:

  1. Normal body temperature for >3 days.
  2. Significant improvement in respiratory symptoms.
  3. Radiographic improvement.
  4. Consecutive 2 negative RT-PCR for 2019-noCoV test, at least 1 day apart.

 

Discharge care:

 

  1. Monitor patient for another 14 days (basically stay at home after discharge, wear a mask at home if living with others, avoid close contact with family members, and avoid going to public areas for another 14 days after discharge).
  2. Return visit in 2-4 weeks.

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