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On January 5, the Critical Care Group of the Respiratory Disease Branch of the Chinese Medical Association and the Critical Care Medicine Expert Group of the Respiratory Physician Branch of the Chinese Medical Doctor Association issued the "Expert Recommendations for the Clinical Treatment of Severe Novel Coronavirus Infection (New Crown) Caused by the Omicron Variant"
.
.
Defined as meeting any of the following criteria: respiratory distress, respiratory rate ≥30 breaths/minute; In the resting state, oxygen saturation ≤ 93% when inhaling air; Arterial partial pressure of oxygen (PaO2)/inspiration concentration (FiO2)≤ 300 mmHg; The clinical symptoms were progressively aggravated, and lung imaging showed that the lesions progressed significantly within 24~48 hours> 50
%.
Adult patients with any of the following are defined as critically ill: respiratory failure requiring mechanical ventilation; Appearance of shock; Other organ failure requires ICU monitoring
.
In order to facilitate rapid clinical assessment of the condition and guide treatment, the severity of the disease can be graded according to whether the oxygen therapy standard (oxygen therapy standard standard: SpO2 is 92%~96%) under different respiratory support conditions: grade 1 does not require oxygen; Grade 2 is nasal cannula oxygen≤ 4 L/min can reach the standard; Grade 3 is oxygen storage mask oxygenation/nasal high-flow humidified oxygen therapy (HFNO)/non-invasive positive pressure ventilation (NPPV) can reach the standard; Grade 4 is invasive ventilator-assisted ventilation or extracorporeal membrane oxygenation (ECMO) assisted
.
Patients with grade 2 and above meet diagnostic criteria
for severe and critical disease.
People of all ages are at potential risk of severe disease from the Omicron variant, especially those who are older, unvaccinated and have underlying medical conditions
.
.
Some patients may have dyspnea and decreased oxygenation after the return of normal temperature, and symptoms of respiratory distress may not be obvious
when oxygenation decreases.
The main signs include increased respiratory rate, no obvious abnormalities in auscultation of both lungs, and crackling sounds
can be heard when changes such as organization and fibrosis occur in the lungs later in the course of the disease.
Extrapulmonary manifestations include cardiovascular complications, including acute coronary syndrome, myocarditis, stress cardiomyopathy, and
arrhythmias.
Studies have shown that different subvariants of Omicron have different replication capabilities in cardiomyocytes cultured in vitro, and some subvariants (such as BA.
5) have enhanced replication, which may be more likely to lead to cardiotoxicity
.
Compared with the original strain, the incidence of pulmonary embolism infection with the Omicron variant was slightly lower, and the risk of developing it was significantly higher in unvaccinated people
.
In terms of inflammatory indicators, studies have shown that interleukin-6 (IL-6) >32.
1 ng/L predicts more serious extrapulmonary organ complications; C-reactive protein defined as a cut-point value of 50 mg/L identifies severe/critical patients
.
Serum ferritin predicts 90-day in-hospital mortality at 714 micrograms/L and invasive mechanical ventilation with a cut-point value of 502 micrograms/L
.
In terms of immune response imbalance index, lymphocyte count <500/μl indicates poor prognosis; A neutrophil-lymphocyte ratio of >2.
973 predicts disease progression
during hospitalization.
In critically ill patients, non-contrast chest CT scan is the preferred option
for the evaluation of Omicron-induced pneumonia.
Anti-inflammatory treatment of glucocorticoids: it is recommended that severe patients start the application as soon as possible, and can choose dexamethasone 5~10 mg/d or methylprednisone 40~80 mg/d, and apply 7~10 days
.
Patients aged > 70 years have limited clinical benefit from glucocorticoids and require strict monitoring for adverse effects
.
JAK inhibitors: for severe patients (grade 2~3), if there are no contraindications, baricitinib 4 mg/d should be used for 14 days
.
Limited use or benefit in mechanically ventilated patients; Use
with caution in immunosuppressed patients.
Tocilizumab: For critically ill patients (grade 2~4) with C-reactive protein ≥ 75 mg/L, if there are no contraindications, it is recommended to apply tocilizumab 8 mg/kg 1~2 times (interval 12~24 h) within 24 hours of ICU admission or 72 hours of general ward admission (interval 12~24 h), and the maximum dose should not exceed 800 mg/time
.
Combination: Glucocorticoids plus JAK inhibitors or tocilizumab are recommended for critically ill patients
.
The combined use
of IL-6 antagonists with JAK inhibitors is not recommended.
3.
Anticoagulation therapy requires individualized assessment
of thrombosis-bleeding risk before determining the strength of anticoagulation.
Aggressive anticoagulation
is recommended in critically ill patients with contraindications.
When suspicion of thromboembolic disease is high but imaging is not complete, subcutaneous anticoagulation of low molecular weight heparin 100 units/kg body weight is recommended
.
For adult, nonpregnant patients who require low-flow oxygen therapy and do not require ICU admission, therapeutic doses of heparin (low molecular weight 100 U/kg body weight 2 times/d subcutaneous injection) are recommended if D-dimer levels are elevated and there is no additional risk of bleeding
.
In non-VTE patients treated with therapeutic doses of heparin anticoagulation, anticoagulation should be continued for 14 days or until they are transferred to the ICU or
discharged.
For those who do not meet the indications for the use of heparin at the therapeutic dose, if there are no contraindications, it is recommended to use low molecular weight heparin 3 000~4 000 U, 1 subcutaneous injection of prophylactic anticoagulation
.
For adult patients who require ICU admission or high-flow oxygen therapy, prophylactic anticoagulation
with low molecular weight heparin 3 000~4 000 U and subcutaneous injection once per day is recommended if there are no contraindications.
For patients who have been initiated on therapeutic dose heparin anticoagulation prior to ICU admission, switching to prophylactic dose heparin anticoagulation after ICU transfer is recommended unless VTE
is confirmed.
Intermediate- or therapeutic-dose anticoagulants are not recommended for VTE prophylaxis
in these patients.
4.
Respiratory support recommends that the oxygenation goal of severe patients maintain SpO2 at 92%~96%.
Ordinary oxygen therapy is difficult to achieve the above oxygenation goals, HFNO is preferred to correct hypoxemia, and indications for treatment include: oxygenation index (PaO2)/inspired oxygen concentration (FiO2) < 300 mmHg, accompanied by respiratory distress symptoms
such as respiratory rate >25 breaths/min or assisted respiratory muscle activity.
NPPV therapy
is preferred in critically ill patients with chronic obstructive pulmonary disease and cardiogenic pulmonary edema.
If HFNO treatment fails or the patient is intolerant, NPPV
can be tried for a short time (1~2 h) under the premise of close monitoring.
Once HFNO or NPPV therapy is ineffective, invasive positive pressure ventilation should be performed as soon as possible to avoid delayed endotracheal intubation and urgent endotracheal intubation
.
Awake prone ventilation is recommended for patients with HFNO with persistent hypoxemia for a duration of 8 hours/day > if possible, but is not a remedy for refractory
hypoxaemia in patients with indications for endotracheal intubation.
In addition to the above respiratory support, the opinion describes invasive positive pressure ventilation and ECMO
.
5.
In the early stage of antibacterial treatment, if there is no evidence of bacterial infection, antibacterial therapy
can not be used.
If concomitant bacterial infection is suspected, penicillins (e.
g.
, amoxicillin/clavulanate), third-generation cephalosporins (e.
g.
, ceftriaxone), or respiratory quinolones can be treated
.
For secondary infection after 48 hours of admission, antimicrobial therapy
is selected according to the local nosocomial epidemiology.
6.
Nutrition therapy for severely ill patients should start enteral nutrition within 24~48 h after entering the ICU, and those who cannot tolerate enteral nutrition can be given parenteral nutrition
.
7.
Severe patients with blood sugar control should control blood sugar at 8~10 mmol
.
.
Definition of severe COVID
.
Defined as meeting any of the following criteria: respiratory distress, respiratory rate ≥30 breaths/minute; In the resting state, oxygen saturation ≤ 93% when inhaling air; Arterial partial pressure of oxygen (PaO2)/inspiration concentration (FiO2)≤ 300 mmHg; The clinical symptoms were progressively aggravated, and lung imaging showed that the lesions progressed significantly within 24~48 hours> 50
%.
Adult patients with any of the following are defined as critically ill: respiratory failure requiring mechanical ventilation; Appearance of shock; Other organ failure requires ICU monitoring
.
In order to facilitate rapid clinical assessment of the condition and guide treatment, the severity of the disease can be graded according to whether the oxygen therapy standard (oxygen therapy standard standard: SpO2 is 92%~96%) under different respiratory support conditions: grade 1 does not require oxygen; Grade 2 is nasal cannula oxygen≤ 4 L/min can reach the standard; Grade 3 is oxygen storage mask oxygenation/nasal high-flow humidified oxygen therapy (HFNO)/non-invasive positive pressure ventilation (NPPV) can reach the standard; Grade 4 is invasive ventilator-assisted ventilation or extracorporeal membrane oxygenation (ECMO) assisted
.
Patients with grade 2 and above meet diagnostic criteria
for severe and critical disease.
People of all ages are at potential risk of severe disease from the Omicron variant, especially those who are older, unvaccinated and have underlying medical conditions
.
Extrapulmonary manifestations in critically ill patients
.
Some patients may have dyspnea and decreased oxygenation after the return of normal temperature, and symptoms of respiratory distress may not be obvious
when oxygenation decreases.
The main signs include increased respiratory rate, no obvious abnormalities in auscultation of both lungs, and crackling sounds
can be heard when changes such as organization and fibrosis occur in the lungs later in the course of the disease.
Extrapulmonary manifestations include cardiovascular complications, including acute coronary syndrome, myocarditis, stress cardiomyopathy, and
arrhythmias.
Studies have shown that different subvariants of Omicron have different replication capabilities in cardiomyocytes cultured in vitro, and some subvariants (such as BA.
5) have enhanced replication, which may be more likely to lead to cardiotoxicity
.
Compared with the original strain, the incidence of pulmonary embolism infection with the Omicron variant was slightly lower, and the risk of developing it was significantly higher in unvaccinated people
.
In terms of inflammatory indicators, studies have shown that interleukin-6 (IL-6) >32.
1 ng/L predicts more serious extrapulmonary organ complications; C-reactive protein defined as a cut-point value of 50 mg/L identifies severe/critical patients
.
Serum ferritin predicts 90-day in-hospital mortality at 714 micrograms/L and invasive mechanical ventilation with a cut-point value of 502 micrograms/L
.
In terms of immune response imbalance index, lymphocyte count <500/μl indicates poor prognosis; A neutrophil-lymphocyte ratio of >2.
973 predicts disease progression
during hospitalization.
In critically ill patients, non-contrast chest CT scan is the preferred option
for the evaluation of Omicron-induced pneumonia.
Clinical treatment of severe disease
1.
Antiviral therapy
For high-risk groups using nematevir/ritonavir and monoravir within 5 days of onset to prevent severe disease (need to be hospitalized or die), it is recommended for patients with new coronavirus infection within 5 days of onset in high-risk factor groups, and patients who have completed 3 doses of vaccination have less benefit from monoravir, and nematevir/ritonavir
can be preferred.
For severely ill patients, who have a > of onset of 5 days but a new coronavirus nucleic acid CT value of < 30, the use of antiviral drugs may still have certain benefits, especially for patients who have not completed three doses of new crown vaccination, combined with the actual situation, the administration time can be extended by one course of treatment
.
Antiviral drugs
may not be used in patients with significantly elevated antibodies.
Ritonavir has interactions with a variety of drugs, and drug interaction screening must be performed during medication, among which drugs of particular concern include statins, new anticoagulants, antiplatelet drugs (clopidogrel, ticagrelol), sedative-hypnotic drugs, calcium antagonists, prostatic prostatic drugs (α receptor blockers), immunosuppressants (calcineurin inhibitors, mTOR inhibitors), antitumor small molecule targeted drugs, azole antifungals, etc
.
Generally, the original treatment can
be resumed after 3 days of discontinuation of nematevir/ritonavir tablets.
In particular, after giving nematevir first, ritonavir must be given within 5 minutes, otherwise the efficacy
of the former will be affected.
Monoravir is not recommended for use in people younger than 18 years of age (which may affect bone and cartilage growth) and in pregnant women (animal studies suggest miscarriage may result).
The monoclonal antibody drugs currently on the market have no neutralizing effect on the Omicron variant, have neither antiviral effect nor preventive effect, so their use
is not recommended.
Gamma globulin and convalescent plasma
are not recommended.
Anti-inflammatory treatment of glucocorticoids: it is recommended that severe patients start the application as soon as possible, and can choose dexamethasone 5~10 mg/d or methylprednisone 40~80 mg/d, and apply 7~10 days
.
Patients aged > 70 years have limited clinical benefit from glucocorticoids and require strict monitoring for adverse effects
.
JAK inhibitors: for severe patients (grade 2~3), if there are no contraindications, baricitinib 4 mg/d should be used for 14 days
.
Limited use or benefit in mechanically ventilated patients; Use
with caution in immunosuppressed patients.
Tocilizumab: For critically ill patients (grade 2~4) with C-reactive protein ≥ 75 mg/L, if there are no contraindications, it is recommended to apply tocilizumab 8 mg/kg 1~2 times (interval 12~24 h) within 24 hours of ICU admission or 72 hours of general ward admission (interval 12~24 h), and the maximum dose should not exceed 800 mg/time
.
Combination: Glucocorticoids plus JAK inhibitors or tocilizumab are recommended for critically ill patients
.
The combined use
of IL-6 antagonists with JAK inhibitors is not recommended.
3.
Anticoagulation therapy requires individualized assessment
of thrombosis-bleeding risk before determining the strength of anticoagulation.
Aggressive anticoagulation
is recommended in critically ill patients with contraindications.
When suspicion of thromboembolic disease is high but imaging is not complete, subcutaneous anticoagulation of low molecular weight heparin 100 units/kg body weight is recommended
.
For adult, nonpregnant patients who require low-flow oxygen therapy and do not require ICU admission, therapeutic doses of heparin (low molecular weight 100 U/kg body weight 2 times/d subcutaneous injection) are recommended if D-dimer levels are elevated and there is no additional risk of bleeding
.
In non-VTE patients treated with therapeutic doses of heparin anticoagulation, anticoagulation should be continued for 14 days or until they are transferred to the ICU or
discharged.
For those who do not meet the indications for the use of heparin at the therapeutic dose, if there are no contraindications, it is recommended to use low molecular weight heparin 3 000~4 000 U, 1 subcutaneous injection of prophylactic anticoagulation
.
For adult patients who require ICU admission or high-flow oxygen therapy, prophylactic anticoagulation
with low molecular weight heparin 3 000~4 000 U and subcutaneous injection once per day is recommended if there are no contraindications.
For patients who have been initiated on therapeutic dose heparin anticoagulation prior to ICU admission, switching to prophylactic dose heparin anticoagulation after ICU transfer is recommended unless VTE
is confirmed.
Intermediate- or therapeutic-dose anticoagulants are not recommended for VTE prophylaxis
in these patients.
4.
Respiratory support recommends that the oxygenation goal of severe patients maintain SpO2 at 92%~96%.
Ordinary oxygen therapy is difficult to achieve the above oxygenation goals, HFNO is preferred to correct hypoxemia, and indications for treatment include: oxygenation index (PaO2)/inspired oxygen concentration (FiO2) < 300 mmHg, accompanied by respiratory distress symptoms
such as respiratory rate >25 breaths/min or assisted respiratory muscle activity.
NPPV therapy
is preferred in critically ill patients with chronic obstructive pulmonary disease and cardiogenic pulmonary edema.
If HFNO treatment fails or the patient is intolerant, NPPV
can be tried for a short time (1~2 h) under the premise of close monitoring.
Once HFNO or NPPV therapy is ineffective, invasive positive pressure ventilation should be performed as soon as possible to avoid delayed endotracheal intubation and urgent endotracheal intubation
.
Awake prone ventilation is recommended for patients with HFNO with persistent hypoxemia for a duration of 8 hours/day > if possible, but is not a remedy for refractory
hypoxaemia in patients with indications for endotracheal intubation.
In addition to the above respiratory support, the opinion describes invasive positive pressure ventilation and ECMO
.
5.
In the early stage of antibacterial treatment, if there is no evidence of bacterial infection, antibacterial therapy
can not be used.
If concomitant bacterial infection is suspected, penicillins (e.
g.
, amoxicillin/clavulanate), third-generation cephalosporins (e.
g.
, ceftriaxone), or respiratory quinolones can be treated
.
For secondary infection after 48 hours of admission, antimicrobial therapy
is selected according to the local nosocomial epidemiology.
6.
Nutrition therapy for severely ill patients should start enteral nutrition within 24~48 h after entering the ICU, and those who cannot tolerate enteral nutrition can be given parenteral nutrition
.
7.
Severe patients with blood sugar control should control blood sugar at 8~10 mmol
.
Source: Critical Care Group, Respiratory Disease Branch of Chinese Medical Association, Critical Care Medicine Expert Group, Respiratory Physician Branch of Chinese Medical Doctor Association.
Expert recommendations for the clinical treatment of severe novel coronavirus infection caused by the Omicron variant.
Chinese Journal of Tuberculosis and Respiratory, 2023, 46: Network prepublication
