Corona Virus 19

Aka: Corona Virus 19, COVID-19, Covid19, SARS-CoV2, Covid-19 Vaccine, Corona Virus 19 Vaccination

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II. Epidemiology

  1. Corona virus that originated in bats (similar to SARS, MERS)
    1. Enveloped, single-stranded RNA novel coronavirus
  2. Originally acquired at seafood and live animal market in Wuhan, Hubei Province, China in late 2019
    1. Initial International hot-spots (Feb 2020): China, Iran, Northern Italy, South Korea, Japan
    2. Initial U.S. hot spots (Feb 2020): Washington and California (sporadic cases in other regions)
      1. By middle March, Corona Virus spread to all 50 states
      2. Limited test availability hampered the identification of true cases, especially given ongoing Influenza

III. Risk Factors: High Risk Patients for Serious Complications (criteria for emergency use Covid medications)

  1. Body Mass Index (BMI) >=35
  2. Chronic Kidney Disease
  3. Diabetes Mellitus
  4. Immunocompromised Condition
  5. Current use of immunosuppressant
  6. Age >=65 years old
  7. Age >= 55 years old AND Comorbidity
    1. Cardiovascular Disease
    2. Hypertension
    3. Chronic Obstructive Pulmonary Disease (or other chronic respiratory disease)
  8. Children 12 to 17 years old with at least one of the following risk factors
    1. Body Mass Index (BMI) >= 85th percentile by age and gender
    2. Sickle Cell Disease
    3. Congenital or acquired heart disease
    4. Neurodevelopmental disorders (e.g. Cerebral Palsy)
    5. Medically related device dependence (e.g. Gastrostomy, Tracheostomy, non-covid related NIPPV)
    6. Asthma, reactive airway disease or other chronic respiratory disease requiring daily medication for control

IV. Pathophysiology: Infectivity

  1. Person to person transmission with viral shedding 17-24 days (median 20 days) in China survivors
    1. Infectious 5 to 13 days after symptom resolution
  2. Infectivity (R0, pronounced "R-Naught")
    1. R0 appears to be 2-3 in most cases of Corona Virus 19
      1. However, there have been "super spreader" cases in which R0>20 (e.g. large gatherings)

V. Pathophysiology: Severe Course Timing

  1. Incubation: 4 to 7 days (mean 5 days, some cases as long as 12-14 days)
  2. Day 0: First Symptoms (see below)
  3. Day 5: Dyspnea
  4. Day 7: Hospital Admission
  5. Day 8: Acute Respiratory Distress Syndrome (ARDS)
  6. Day 12-18: Death
  7. Day 22: Survivor hospital discharge
  8. Day 30: Recovery in mild cases (although Anosmia may persist for months)
  9. Day 60-75: Recovery in severe cases

VI. Pathophysiology: Illness stages

  1. Replication Stage
    1. Virus replicates with relatively minor symptoms
  2. Immunologic Response Stage
    1. Immune response after the first few days to week is a normal adaptive response in 80% of patients
    2. Exaggerated immunopathologic response (Cytokine Storm) occurs in <20% of cases
      1. See Cytokine Release Syndrome (Cytokine Storm)
      2. Inflammatory Cytokines cause tissue damage with Pneumonia and ARDS

VII. Findings: Signs and Symptoms in Adults

  1. General and prodromal
    1. Asymptomatic in 18-33% (especially younger patients)
    2. Fever (44% at initial presentation, 83-98% on hospitalization)
    3. Chills (12%)
    4. Myalgias (11 to 45%)
    5. Fatigue (38 to 70%)
    6. Anorexia (40%)
  2. Upper Respiratory
    1. Pharyngitis (5-14%)
    2. Nasal congestion or Rhinorrhea (2 to 5%)
    3. Conjunctivitis (1%)
  3. Cardiopulmonary
    1. Cough (46-82%)
      1. Hemoptysis (1-2%)
      2. Cough is typically dry (but may be productive in up to one third of cases)
    2. Shortness of Breath (31%)
      1. Associated with more severe disease
    3. Hypoxia (9% of mild cases, 40% of severe cases)
      1. Patients often appear to be in little respiratory distress
      2. Yet patients often present with profound Hypoxia (even with O2 Sat 70-80%)
      3. Patients with significant respiratory distress may decompensate rapidly
  4. Cardiac
    1. Chest tightness, pain or pressure (2 to15%)
    2. Palpitations
  5. Gastrointestinal
    1. Decreased appetite or Anorexia (40%)
    2. Diarrhea (17%)
    3. Nausea and Vomiting (up to 19%)
  6. Neurologic
    1. Headache (3-14%)
    2. Confusion or Altered Level of Consciousness (encephalopathy)
    3. Dizziness (8%)
    4. Altered taste or smell (34-64% of patients)
      1. Loss of Smell Sensation (Anosmia)
      2. Altered Taste Sensation (Dysgeusia)
  7. Skin
    1. Rash (up to 20% of cases)
    2. Pernio-like reactions of distal digits with erythema and swelling ("Covid Toes")
    3. Acrocyanosis
    4. Livedo Reticularis

VIII. Findings: Signs and Symptoms in Children

  1. Pharyngeal erythema (46%)
  2. Cough (44 to 54%)
  3. Fever (41-56%)
  4. Diarrhea (8%)
  5. Vomiting
  6. Fatigue (8%)
  7. Rhinorrhea (8%)

IX. Precautions: Red Flag Findings Prompting Emergent Evaluation (Triage Protocols, return indications)

  1. Vital Signs
    1. Heart Rate >110
    2. Respiratory Rate >22
    3. Oxygen Saturation <93%
    4. Systolic Blood Pressure <100 mmHg
    5. Minimal to no Urine Output
  2. Cardiopulmonary
    1. Hemoptysis
    2. Severe Chest Pain or pressure
    3. Severe Shortness of Breath at rest
  3. Skin
    1. Cyanosis
    2. Cold, clammy, pale or mottled skin
    3. Non-blanching rash
  4. Mental status
    1. Lethargy or difficult to arouse
    2. New confusion

X. Labs

  1. COVID-19 Diagnosis (efficacy varies widely by test version, technique, timing)
    1. Indications for COVID-19 Testing (Antigen or PCR)
      1. Symptomatic patients
      2. Asymptomatic patients undergoing hospitalization or procedures
      3. Asymptomatic patients with known positive exposure >15 min (esp. indoors without mask or social distancing)
        1. Avoid testing within first 48 hours (high False Negative Rate)
        2. Consider testing at 3-5 days and 7-10 days after exposure
        3. Quarantine for 10-14 days after exposure and a positive Covid test
        4. Quarantine for 7-10 days after negative Covid PCR at 5-7 days after exposure
      4. No need to re-test patients after positive test (use 10 day quarantine guidelines below)
        1. Tests may remain positive for weeks
      5. Re-exposed patients after positive COVID-19 Test need not be re-tested within first 3 months
        1. Persistent positive tests may confuse results and Immunity is likely for at least 3 months
      6. (2020) Presc Lett 27(10): 55
    2. Molecular PCR for Corona Virus 2019 (preferred)
      1. Reverse transcriptase polymerase chain reaction detects viral nucleic acids that are amplified in sample
      2. Obtained via Nasopharyngeal swab (deep nasal swab) or Oropharyngeal swab
      3. Test accuracy depends on an adequate swab sample
      4. FDA approved PCR tests have Test Sensitivity >95%, Test Specificity >98%
    3. Antigen Tests for Corona Virus 2019
      1. Obtained via Nasopharyngeal swab (deep nasal swab) or Oropharyngeal swab
      2. Fast and inexpensive tests similar to Rapid Strep Test and Rapid Influenza Test (but lower efficacy than PCR)
      3. Increased risk of False Negative 5-12 days after symptom onset (falling viral loads)
        1. Molecular (PCR) tests are less effected by this timing
        2. Consider repeating as a Molecular test after initial Antigen testing is negative
      4. Lower Test Sensitivity: 70-80% in symptomatic patients
        1. Test Sensitivity drops to 35-40% in asymptomatic patients
      5. High Test Specificity: >98%
    4. Antibody Testing (IgG and IgM) for Corona Virus 2019
      1. Unclear if Antibody confers Immunity
      2. Unclear how long Antibody confers Immunity (may be short as with seasonal Influenza)
      3. FDA approved Antibody tests should have Test Sensitivity >90% and Test Specificity >95%
      4. High False Positive Rate (20-30%) in low disease Prevalence regions (much of U.S. in Fall 2020)
      5. Consider testing patients with repeatedly negative Antigen tests, but persistent symptoms for weeks
    5. Home Testing (OTC)
      1. Precautions
        1. Most accurate in symptomatic, non-immunized patients
        2. False Negatives may occur and unlikely to be accepted for travel requirements
        3. False Positives may occur in up to 30% of asymptomatic patients (confirm with PCR)
      2. Simple Antigen Tests (similar to home Pregnancy Test)
        1. Antigen test requiring nasal sample
        2. Similar to Pregnancy Test with result in 15 minutes
        3. Cost: $20-30 for 2 tests
        4. Devices
          1. BinaxNow (Test Sensitivity 85%, Test Specificity 99%)
          2. QuickVue (Test Sensitivity 96%, Test Specificity 99%)
      3. Ellume
        1. Rapid Antigen test approved for age > 2 years, results in 15 min, costs $40 OTC
        2. Requires a mid-turbinate sample and a smartphone (connects to analyzer via bluetooth)
        3. Test Sensitivity 80%
        4. Test Specificity approaches 100% in patients with symptoms, BUT False Positives if no symptoms
    6. References
      1. (2021) Presc Lett 28(6): 33-4
      2. (2021) Presc Lett 28(2): 10
  2. Differential Diagnosis Evaluation
    1. Influenza nasopharyngeal swab
      1. Coninfection with Influenza is unlikely but possible (may occur in 5% of cases)
    2. Respiratory Virus Panel
      1. Typically includes Influenza, parainfluenza, RSV, Metapneumovirus, Rhinovirus, Adenovirus
    3. Pertussis PCR
    4. Streptococcal Pneumoniae urine Antigen
    5. Legionella urine Antigen
  3. Other lab findings
    1. Complete Blood Count (CBC) with Platelet Count
      1. Lymphopenia (Lymphocytes <1500/mm3) is most common (63%)
        1. More common in worse disease (present in >80% of those hospitalized)
      2. Leukocytosis (24-30%)
      3. Thrombocytopenia (associated with worse prognosis)
    2. Liver Function Test
      1. Liver transaminases (AST, ALT) mildly increased (37%)
      2. Lactate Dehydrogenase
    3. Venous Blood Gas
    4. Serum Lactate
  4. Acute phase reactants
    1. C-Reactive Protein
    2. Serum Ferritin
    3. Procalcitonin
      1. Normal on presentation
      2. Increase may suggest Bacterial Infection or severe Covid19 infection
  5. Markers of increased mortality
    1. D-Dimer (increased >1)
      1. D-Dimer >1.5 mcg/ml may prompt prophylactic Anticoagulation at some facilities
    2. Serum Troponin Increased
    3. Lymphopenia (Lymphocytes <1500/mm3)
    4. Interleukin-6 (IL-6) Increased
    5. Liver Function Test increases (AST, ALT, LDH, PT/INR increased)
    6. Serum Creatinine increased
    7. Creatine Kinase (CK) increased
    8. Serum Ferritin increased
    9. Procalcitonin Increased
  6. Other testing
    1. Blood Cultures (draw and hold first set with initial lab testing)

XI. Imaging

  1. Chest XRay
    1. Bilateral infiltrates
  2. Chest CT
    1. Bilateral regions of lung consolidation and ground glass opacities
    2. Progression from scattered ground glass findings to coalescence and then lung consolidation in the most severe cases
  3. Lung Ultrasound
    1. Survey the lungs using a systematic "lawn mower" approach
    2. Ultrasound B-Line artifacts correlate with CT ground glass findings
    3. Progression from scattered b-line artifacts to b-line coalescence and then lung consolidation (liver-like appearance)
    4. https://emcrit.org/ibcc/COVID19/#lung_ultrasonography

XII. Differential Diagnosis

  1. See Hypoxia
  2. See Dyspnea
  3. Bacterial Infections
    1. Streptococcal Pneumoniae
    2. Pertussis
    3. Legionella pneumonia
    4. Streptococcal Pharyngitis
    5. Opportunistic lung infection
  4. Viral Respiratory Infections
    1. Influenza
    2. Parainfluenza
    3. Metapneumovirus
    4. Rhinovirus
    5. Adenovirus
  5. Non-Infectious Causes
    1. Pulmonary Embolism
    2. Obstructive Lung Disease (Asthma Exacerbation, COPD exacerbation)
    3. Congestive Heart Failure with Acute Pulmonary Edema
    4. Acute Respiratory Distress Syndrome

XIII. Complications: Acute

  1. Precautions
    1. Complications and decompensation are more common after 7 days of illness
    2. Prolonged symptoms (>14-21 days) in up to 35% of cases
  2. Respiratory Effects
    1. Multi-lobar Pneumonia
    2. Acute Respiratory Distress Syndrome (ARDS)
  3. Cardiac effects
    1. Myocarditis (Cardiomyopathy with Cardiogenic Shock)
      1. May mimic Acute Coronary Syndrome (findings on EKG may be identical to STEMI)
    2. Acute Coronary Syndrome
      1. Like Influenza, COVID-19 creates a severe inflammatory response that precipitates Plaque rupture and MI
      2. Cardiology is unlikely to perform PCI on active COVID-19 patients
        1. May need to consider MI Thrombolysis (however, high risk in patients at risk of DIC)
  4. Thrombosis
    1. Venous Thromboembolism
    2. Mycocardial Infarction
    3. Cerebrovascular Accident
    4. Skin microthrombi such as Pernio (see dematologic findings as above)
    5. https://www.sciencedirect.com/science/article/pii/S0049384820301201
  5. Encephalopathy
    1. Filatov (2020) Cureus 12(3):e7352 +PMID:32328364 [PubMed]
  6. Multisystem Inflammatory Syndrome (similar to Kawasaki Disease)
    1. Prolonged Fever, severe illness and multiorgan involvement
    2. Jones (2020) Hosp Pediatr +PMID:32265235 [PubMed]
  7. Acute Renal Failure
    1. Raza (2020) Cureus 12(6):e8429 +PMID:32642345 [PubMed]

XIV. Complications: Chronic

  1. See ICU Follow-up Care
  2. Background
    1. Post-Covid Long-Term Effects ("Long Haulers") occurs in approximately 10% of Covid Patients
    2. Although there are many Chronic Complications of ICU Care, Post-Covid effects are often seen in less severe cases
  3. Common Symptoms in those with Chronic Findings
    1. Fatigue (58%)
    2. Headache (44%)
    3. Attention disorder (27%)
    4. Alopecia (25%)
    5. Dyspnea (24%)
    6. Lopez-Leon (2021) medRxiv +PMID: 33532785 [PubMed]
  4. Associated Conditions
    1. Respiratory
      1. DLCO Decreased on Pulmonary Function Testing
      2. Decreased lower respiratory Muscle Strength
      3. Persistently abnormal CT Chest
      4. Huang (2020) Respir Res 21(1):163 +PMID: 32600344 [PubMed]
      5. Lerum TV (2020) Eur Respir J +PMID: 33303540 [PubMed]
    2. Cardiovascular
      1. Persistent Myocarditis
      2. Puntmann (2020) JAMA Cardiol 5(11):1265-73 [PubMed]
      3. Rajpal (2021) JAMA Cardiol 6(1):116-8 [PubMed]
    3. Neurologic
      1. Cognitive Difficulties
      2. Memory Difficulties
      3. Anosmia
        1. Otte (2020) J Infect 81(3):e58 +PMID: 32592702 [PubMed]
    4. Psychiatric
      1. Anxiety
      2. Post-Traumatic Stress Disorder
    5. Resources
      1. Post-Covid (CDC)
        1. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html
    6. References
      1. Fernandez (2021) Sao Paulo Med. J. 139 +PMID:33656121 [PubMed]

XV. Management: General Measures

  1. See Prevention below
    1. Includes Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing
  2. TeleHealth triage protocol
    1. Mild symptoms
      1. COVID testing
      2. Self-care (e.g. deep breathing Exercises and position changes - see below)
      3. Quarantine (see below)
      4. Monitor symptoms, signs and oyxgen saturation probe (if available) and return if consistently <92%
      5. Telephone Follow-up
    2. Moderate Symptoms
      1. Outpatient, in-person visit
    3. Severe Symptoms (esp. with comorbidities) or Red Flags (see above)
      1. Emergency Department evaluation
  3. Position Changes
    1. Consider awake prone position (as well as on their left and right lateral decubitus positions, and sitting upright)
    2. Direct patient to roll to prone position and other positions for as long as they are comfortable
    3. Proning obese patients may be difficult
      1. Consider pregnancy massage mattress
      2. https://prone2help.org
  4. Practice deep breathing Exercises
    1. Johns Hopkins
      1. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/coronavirus-recovery-breathing-exercises#:~:text=Phase%201%3A%20Deep%20Breathing%20While%20On%20Your%20Back&#38;text=Breathe%20in%20through%20the%20nose,deep%20breaths%20for%20one%20minute.
  5. Disposition: Home Recommendations
    1. High Risk Patients (see Risk Factors Above)
      1. Monoclonal Antibodies (see below)
    2. Practice position changes and deep breath Exercises (see above)
    3. Monitor for Hypoxia (with portable Oxygen Saturation monitor)
      1. Return for Oxygen Saturations <92%
    4. Duration of home quarantine recommendations
      1. Asymptomatic contacts
        1. Monitor for fever and possible COVID-related symptoms daily
        2. Quarantine for 7 days after last exposure IF 2 criteria
          1. Patient remains symptom-free AND
          2. Negative Covid Antigen or PCR test on day 5-6 post-exposure
      2. Symptomatic patients or positive COVID test
        1. Quarantine >= 10 days and no fever for at least 1 day (was 3 days) AND improving symptoms (e.g. cough)
          1. Quarantine for at least 20 days if severely immunocompromised
        2. Isolate within home, staying in sick area/room away from others and without sharing bathroom
      3. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html

XVI. Management: Emergency Department Overall Approach

  1. See ABC Management
  2. See Intensive Care
  3. See Pneumonia Management
  4. See ARDS Management
  5. Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing - see below
  6. Avoid aggressive fluid Resuscitation (do NOT use Sepsis level 30 cc/kg)
  7. Have Norepinephrine available for Hypotension

XVII. Management: Oxygenation

  1. Precautions
    1. Oxygenation combined with position changes (see above) are the two most critical interventions
    2. Monitor oxygenation and ventilation closely and recheck patient every 1-2 hours (patient decompensate quickly)
    3. Review work of breathing, Respiratory Rate, Heart Rate, Oxygen Saturation, Capnography and other parameters
    4. Consider Endotracheal Intubation in those tiring, failing oxygenation strategies
  2. Oxygenation by Nasal Cannula and Mask
    1. Oxygen by Nasal Cannula up to 5-6 L/min (humidified if available) to maintain Oxygen Saturation 92-96%
    2. Persistent Hypoxia despite Nasal Cannula up to 5-6 L/min
      1. Non-rebreather at 15 L/min may be applied over the top of the Nasal Cannula
        1. Helps prevent aerosolization
        2. Allows for adequate oxygenation for severe Hypoxia
        3. Levitan (2020) ACEP Now (see link below)
      2. Non-Invasive Positive Pressure Ventilation (esp. HHFNC, or in some cases non-vented CPAP)
      3. Endotracheal Intubation
  3. Non-Invasive Positive Pressure Ventilation (NIPPV)
    1. Use all devices with viral filter (HEPA filter)
    2. High Flow Nasal Cannula (typically 40 to 60 L/min)
      1. Appears safer than BiPAP, CPAP without significant viral dispersion
      2. Allows for the oxygenation and increased alveolar recruitment that many with corona virus require
      3. However, anecdotally at high volume sites, High Flow Nasal Cannula appears less effective than CPAP
    3. CPAP
      1. Risk of viral dispersion
      2. If done safely, CPAP could have a significant role for alveolar recruitment
        1. https://emcrit.org/pulmcrit/cpap-covid/
      3. Safer options to limit viral dispersion
        1. Non-vented CPAP masks
        2. Helmet interface (used in Italy pandemic, not typically available in U.S.)
    4. BIPAP is not recommended
      1. CPAP alone appears adequate to overcome Atelectasis and surfactant loss
      2. BiPAP appears to add little benefit in Covid19 over CPAP, with the risk of virus dispersion

XVIII. Management: Endotracheal Intubation

  1. Precautions
    1. Although early intubation has been favored, NIPPV despite Hypoxia may be preferred in some patients
    2. Endotracheal Intubation is among the highest risk procedures for transmission
    3. COVID-19 patients are intubated on Mechanical Ventilation for on average 10 days
      1. See Mechanical Ventilation for potential complications
      2. Mortality of intubated patients ranges from 20-90%
    4. COVID-19 patients are difficult intubations (most experienced intubating clinician should perform)
      1. Rapid desaturation despite Apneic Oxygenation
      2. Signficant airway edema of the supraglottic region that distorts landmarks
        1. Elastic Bougie has been less helpful in these patients (not firm enough given edema)
    5. Maximize Endotracheal Tube first pass success
      1. Slow down and expect desaturation with intubation
      2. Exercise caution in Laryngoscope introduction, rotating around the Tongue
      3. Use the Levitan technique of gradual exposure of the uvula, epiglottis, aryepiglottic fold, Larynx
    6. Avoid Awake Nasotracheal Intubation
      1. Higher risk of aerosolization
      2. Nasal Intubation duration limit of 3 days is too short for COVID-19 patients
    7. Have rescue airway at bedside
      1. Attach I-Gel or LMA with HEPA Filter to ambubag with PEEP Valve
  2. Early intubation has been advocated over NIPPV (other than High Flow Nasal Cannula) for less viral transmission
    1. However, intubation puts healthcare staff at significant transmission risk
    2. Ventilators are a limited resource (Italian providers placed up to 4 patients on the same Ventilator)
      1. https://emcrit.org/pulmcrit/split-ventilators/
  3. Have a lower threshold for intubation when failing High Flow Nasal Cannula
    1. COVID-19 patients may give less warning (Hypoxemia without increased resp. effort) before rapid decompensation
    2. Rising FIO2 requirements (>75% FIO2) and high Respiratory Rate >26/min
  4. Personal Protection Equipment (PPE)
    1. See Donning and Doffing Personal Protection Equipment
    2. Providers are using Powered Air Purifying Respirator (PAPR) for intubation where available
    3. Surgical hat and gown
    4. N95 Mask beneath a surgical mask with Face Shield
      1. Ideally uses a full Face Shield or goggles
    5. Double gloves
  5. Intubation Equipment
    1. Video Laryngoscopy is preferred (allows for distance from airway) over Direct Laryngoscopy
      1. However, supraglottic inflammation or restricted mouth opening may require Direct Laryngoscope backup
      2. Consider Macintosh-Shaped Video Laryngoscopy blades (may also be used with Elastic Bougie)
    2. Endotracheal Tube with stylet and 10 cc syringe
    3. HEPA Filter
    4. CO2 Detector
    5. Dirty equipment bucket at feet of intubating provider
    6. Rescue Airway (e.g. I-Gel or LMA with HEPA Filter)
    7. Preoxygenation equipment (see below)
      1. Bag-Valve Mask (BVM) with PEEP Valve
      2. EtCO2 adapter (inline between Bag and Mask)
        1. Oxygen tubing attached and oxygen flow set at 6 L/min
      3. Viral Filter (inline between Bag and Mask)
      4. Mask
        1. Use NIPPV mask if available for better seal
  6. Rapid Sequence Intubation (with K-ROC)
    1. Ketamine and Rocuronium is the a common Sedative and paralytic combination used in these intubations
    2. Ketamine 1.5 to 2 mg/kg
    3. Rocuronium 1.5 to 2 mg/kg
  7. Preoxygenation
    1. Preoxygenation for 5 minutes without Positive Pressure Ventilation
    2. Continue Apneic Oxygenation throughout intubation, despite with expect rapid oxygen desaturation
    3. Use Rapid Sequence Intubation with Apneic Oxygenation, but avoid PPV (Bag Valve Mask or Bipap)
      1. However, Scott Weingart, MD has an innovative approach to safe preoxygenation with CPAP
      2. https://emcrit.org/emcrit/covid19-intubation-packs-and-preoxygenation-for-intubation/
  8. Safe PPE Procedure after passing Endotracheal Tube
    1. Inflate ET Tube cuff and dispose of syringe
    2. Drop stylet and Laryngoscope Blade into the dirty equipment bucket
    3. Place Laryngoscope Handle onto work surface now considered dirty
    4. Remove outer gloves
    5. Attach HEPA Filter to ET Tube (will remain in place throughout Mechanical Ventilation period)
    6. Attach CO2 detector and ambubag to confirm color change
    7. Remove only the CO2 detector (leave HEPA Filter in place) and continue ventilation
    8. Carefully evaluate ET Tube Depth (CXR may be delayed)
  9. Mechanical Ventilator settings
    1. See Mechanical Ventilation
    2. Follow ARDSnet protocols
    3. Initial Setting
      1. Use low Tidal Volumes (e.g. 6 ml/kg Ideal Body Weight)
      2. Use high Respiratory Rates (e.g. 20/min)
        1. However monitor closely for Breath Stacking (Auto-PEEP)
        2. Monitor for Hypotension (decreased Preload)
      3. May start with high FIO2 but rapidly decrease FIO2 while increasing PEEP
        1. See PEEP Table
        2. Goal Oxygen Saturation 92 to 96%
        3. FIO2 <0.4, Start with PEEP 5 cmH2O
          1. Consider Ventilator Weaning if stable on low FIO2 and low PEEP (see below)
        4. FIO2 0.4 to 0.6, Start with PEEP 10 cmH2O
          1. See Ventilator Troubleshooting (evaluate for mucous plugging, Pneumothorax, VAP)
        5. FIO2 >0.6, Start with PEEP 15 cmH2O
          1. Prone patient for 16 hours of every 24 hours if FIO2 >0.6 and PEEP >10 cmH2O
          2. Consider ECMO if persistent FIO2 and PEEP requirements
      4. Inspiratory to Expiratory Ratio (I:E) to 1:2 or 1:1.5
    4. Consider a lung recruitment maneuver at start of Mechanical Ventilation
      1. Increase Tidal Volume to 8-10 ml/kg for 10 minutes and then return to 6 ml/kg OR
      2. Increase pressure to 30 cm H2O for 30 seconds
    5. Ventilator Weaning
      1. Consider when FIO2 <0.5 and PEEP <10 cmH2O
      2. Decrease sedation and trial pressure support
    6. Monitoring
      1. Permissive hypercapnea, but keep pH >7.2 (permissive hypercapnea)
      2. Plateau pressure <30 cm H2O
      3. Follow ABG every 12 hours (and as needed for clinical worsening)
    7. Inadequate Ventilators available
      1. See Ventilator Sharing
  10. Post-Intubation Sedation and Analgesia
    1. Inadequate sedation risks Post-Traumatic Stress Disorder
    2. Expect to use higher doses of sedation
      1. Patients have Respiratory Failure, but intact mentation
      2. Plan to sedate to RASS -3 to -5 (Deep Sedation )
    3. Start with Propofol and Fentanyl
    4. Add Dexmedetomidine or Midazolam

XIX. Management: Lines and Fluids

  1. Left Internal Jugular Central Line
    1. Reserve right internal jugular for ECMO
  2. Arterial Line
  3. Nasogastric Tube or Orogastric Tube
  4. Urinary Catheter
  5. Maintain negative flud balance
    1. Avoid maintenance Intravenous Fluids
    2. Supply fluids through enteral feedings and the fluid in delivered medications
    3. Consider IV Furosemide (lasix) 20 mg every 8 hours
    4. If fluid bolus is required, use 20% Human Albumin
  6. Enteral Feedings (Nasogastric Tube)
    1. Use calorie dense feedings, targeting 25 kcal/kg/day
    2. Use senna 15 ml twice daily to promote regular stooling once enteral feeds are established
      1. Consider adding Lactulose

XX. Management: Adjunctive Measures

  1. Bronchodilators
    1. Avoid nebulizer use due to dispersion of virus
    2. Albuterol HFA Inhaler as needed
  2. Corticosteroids
    1. Dexamethasone
      1. Indicated in COVID-19 Patients on Supplemental Oxygen or Mechanical Ventilation
      2. Dosing: Dexamethasone 6 mg daily for up to 10 days
      3. https://www.covid19treatmentguidelines.nih.gov/dexamethasone/
      4. Horby (2020) N Engl J Med +PMID:32678530 [PubMed]
    2. Other Corticosteroid indications
      1. May also use Corticosteroids in those with Asthma Exacerbation or COPD exacerbation
      2. Intensivists have also used Methylprednisolone 60 mg IV daily for 3-6 days in severe ARDS
    3. Corticosteroids are not recommended early in COVID-19 course for those not with indications above
      1. Risk of increased viral shedding, worse outcomes
  3. Specific measures under investigation
    1. Monoclonal Antibodies
      1. Seemed very promising for COVID-19 treatment as of December 2020
        1. Monoclonal Antibody helps prevent SARS-CoV-2 from entering the cell
        2. However results have been surprisingly mediocre
          1. https://emcrit.org/pulmcrit/bamlanivimab/
      2. FDA Emergency Use Indications (none are FDA approved for routine use in December 2020)
        1. Confirmed positive COVID-19 testing AND
        2. High Risk Patients for Serious Complications (see Risk Factors as above) AND
        3. Patient NOT hospitalized for COVID-19 AND
        4. Patient not requiring Supplemental Oxygen for COVID-19
          1. No increase in Supplemental Oxygen if chronic use (e.g. oxygen dependent COPD)
      3. Preparations (Outpatient Infusions)
        1. General
          1. Age>=12 years old AND weight >=40 kg
          2. Recommended as soon as possible (within 10 days of symptom onset)
          3. Rare Hypersensitivity Reactions have occurred
          4. As of January 2021, many insurers in U.S. are covering doses
          5. Defer Covid-19 Vaccination for at least 90 days after Monoclonal Antibody dose
            1. These monoclonal antibodies may interfere with Vaccine immune response
        2. Combination Casirivimab and Imdevimab (Regeneron product)
          1. Casirivimab 1200 mg and Imdevimab 1200 mg infused over 1 hour
          2. https://www.covid19treatmentguidelines.nih.gov/statement-on-casirivimab-plus-imdevimab-eua/
        3. Combination: Bamlanivimab and Etesevimab
          1. Early data with possible mortality reduction of 2%
          2. (2021) Presc Lett 28(4):20-1
        4. Bamlanivimab (Lilly product, LY-COV555)
          1. Bamlanivimab 700 mg in 20 ml infused over 1 hour
          2. Replaced by combination product with Etesevimab
          3. https://www.covid19treatmentguidelines.nih.gov/statement-on-bamlanivimab-eua/
    2. Convalescent Plasma
      1. Shen (2020) JAMA +PMID:32219428 [PubMed]
    3. Remdesivir
      1. Viral RNA Polymerase Inhibitor (nucleotide analog prodrug) that inhibits viral RNA synthesis
        1. Originally developed for use in Ebola
        2. May speed COVID-19 Recovery, but unclear if affects mortality
      2. Indicated in moderate Covid with Hypoxia, bilateral lung involvement, or severe cases
      3. Dosing: 200 mg IV (or 10/mg/kg) for 4-9 days
      4. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
      5. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
  4. Specific measures pending further study
    1. Ivermectin
      1. Insufficient evidence to support use as of January 2021, pending further research
      2. https://www.covid19treatmentguidelines.nih.gov/statement-on-ivermectin/
  5. Specific measures that do not appear effective (or for which risk is worse than benefit)
    1. Chloroquine or Hydroxychloroquine
      1. Mortality may be higher (low efficacy, adverse effects) with these drugs despite promising results in early studies
      2. Chloroquine and Hydroxychloroquine have numerous adverse effects (e.g. QTc Prolongation)
      3. https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2
      4. https://wattsupwiththat.com/2020/03/17/an-effective-treatment-for-coronavirus-covid-19-has-been-found-in-a-common-anti-malarial-drug/
    2. Azithromycin
      1. Results as of May 2020 are not promising
      2. Initial trials combined with Chloroquine showed possible improved outcomes
        1. Gautret (2020) Int J Antimicrob Agents +PMID:32205204 [PubMed]
      3. However, there is risk of Ventricular Arrhythmia related to QTc Prolongation with this combination
        1. https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19
    3. Lopinavir/Ritonavir (Kaletra, LPV/r)
      1. As of May 2020 studies demonstrate no significant efficacy, and risk of Drug Interactions
        1. Ritonavir has many Drug Interactions
        2. Cao (2020) N Engl J Med +PMID: 32187464 [PubMed]
      2. Was initially considered when Chloroquine was not available
        1. Young (2020) JAMA
        2. https://jamanetwork.com/journals/jama/fullarticle/2762688
    4. Tocilizumab
      1. Anti-IL6 Monoclonal Antibody used in Cytokine Release Syndrome
      2. Studied in COVID-19 as of March 2020 (phase 3 trial)
        1. https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia
      3. Does not appear effective in severe COVID-19
        1. Stone (2020) N Engl J Med 383:2333-44 [PubMed]
  6. Other measures that have been used with poor evidence
    1. Zinc Supplementation
    2. Vitamin C 1.5 g IV every 6 hours
    3. Thiamine 200 mg IV every 12 hours
  7. Medications with unclear risk
    1. NSAIDs
      1. Early in COVID-19 course, some postulated risk of NSAIDs, but no current evidence of risk as of May 2020
      2. Use Acetaminophen as a first-line Analgesic, but NSAIDs are not currently contraindicated in COVID-19
    2. ACE Inhibitors and Angiotensin Receptor Blockers (ARBs)
      1. Coronavirus targets ACE-2 Receptors as an entry into cell
      2. Postulated that ACE Inhibitors might up-regulate ACE Receptors
      3. No evidence as of significant benefit or harm of these agents as of May 2020
  8. Indications for empiric Community Acquired Pneumonia treatment
    1. Imaging consistent with Pneumonia
    2. Procalcitonin >0.26 ng/ml

XXI. Prognosis: Severe Cases

  1. Severe disease in 14% of patients
    1. ICU admission in 5% of adults and 2% of children
      1. Of children requiring hospitalization, 1 in 3 require ICU level care
  2. Risks for complications or more serious, progressive infection or death
    1. Male gender
    2. Older age (60 years and older)
    3. Comorbidity (e.g. Hypertension, Diabetes Mellitus, Cardiovascular Disease, Renal Disease, Liver Disease, COPD)
      1. Hospitalized patients: 23 to 71% have at least one comorbid condition
      2. ICU Patients: 43 to 78% have at least one comorbid condition
      3. Mortality: >94% have at least one comorbid condition
    4. Body Mass Index (BMI>30)
    5. Obstructive Sleep Apnea
    6. Tobacco Abuse
      1. Smoking confers more severe case (RR 1.4)
      2. Smoking confers increased risk of ICU admission, Mechanical Ventilation and death (RR 2.4)
      3. Vardavas (2020) Tob Induc Dis 18:20 [PubMed]
    7. Immunocompromised patients (e.g. HIV, Autoimmune Disease, cancer, immunosuppressants)
    8. Pregnancy (or first 2 weeks postpartum)
    9. Sickle Cell Anemia
    10. D-Dimer >1 on admission
    11. SOFA Score high
  3. Age-Related Prognosis
    1. Age <20 years
      1. Hospitalizations: 1.6 to 2.5%
      2. ICU admissions: 0
      3. Deaths: 0
    2. Age 20-44 years
      1. Hospitalizations: 14.3 to 20.8%
      2. ICU admissions: 2.0 to 4.2%
      3. Deaths: 0.1 to 0.2%
    3. Age 45 to 54 years
      1. Hospitalizations: 21.2 to 28.3%
      2. ICU admissions: 5.4 to 10.4%
      3. Deaths: 0.5 to 0.8%
    4. Age 55 to 64 years
      1. Hospitalizations: 20.5 to 30.1%
      2. ICU admissions: 4.7 to 11.2%
      3. Deaths: 1.4 to 2.6%
    5. Age 65 to 74 years
      1. Hospitalizations: 28.6 to 43.5%
      2. ICU admissions: 8.1 to 18.8%
      3. Deaths: 2.7 to 4.9%
    6. Age 75 to 84 years
      1. Hospitalizations: 30.5 to 58.7%
      2. ICU admissions: 10.5 to 31.0%
      3. Deaths: 4.3 to 10.5%
    7. Age >85 years
      1. Hospitalizations: 31.3 to 70.3%
      2. ICU admissions: 6.3 to 29.0%
      3. Deaths: 10.4 to 27.3%
  4. Post-ICU Survivor Care (and post-hospitalization)
    1. See ICU Follow-up Care
    2. See Chronic Complications as above
    3. Consider virtual visit for initial follow-up
    4. Isolate patients severe Critical Illness or immunocompromised state should quarantine for 20 days (instead of 10)
    5. Gradual return to activity once patient is asymptomatic for 2 weeks and reassuring Troponin, ekg, Echocardiogram
      1. Consider post-ICU physical rehabilitation (may be directed by Telemedicine)
      2. Avoid competitive or strenuous Exercise in recovery period (Covid risk of Myocarditis or Cardiomyopathy)
    6. Discharge to Nursing Home
      1. Staff must have appropriate PPE to care for patient
      2. Facility must have capacity to quarantine patient per CDC guidelines without exposing other residents
  5. References
    1. (2020) MMWR Morb Mortal Wkly Rep 69(12):343-6 [PubMed]
    2. Wilbur (2021) Am Fam Physician 103(10): 590-6 [PubMed]

XXII. Prognosis: Mortality

  1. Large number of asymptomatic and undiagnosed cases makes mortality estimate difficult
    1. Mortality overall 0.6 to 0.9% based on extrapolated undiagnosed cases
  2. Mortality (Worldwide)
    1. France: 15.3%
    2. Italy: 14.4%
    3. U.K.: 14.1%
    4. Mexico: 11.7%
    5. Sweden: 10.4%
    6. Ecuador: 8.4%
    7. Canada: 8.1%
    8. U.S.: 5.7%
    9. Johns Hopkins Coronavirus Resource Center (accessed 6/9/2020)
      1. https://coronavirus.jhu.edu/data/mortality
  3. Mortality: Cohorts
    1. See Severe Cases above for comorbidity related mortality risks
    2. By Age
      1. Age <=54 years old: <1% Mortality
      2. Age 70-79 years old: 8% Mortality
      3. Age >80 years old: 10-27% Mortality
    3. By Age in ICU
      1. Age 16 to 49 years old: 25%
      2. Age 50 to 59 years old: 41%
      3. Age 60 to 69 years old: 56%
      4. Age >70 years old: 69%
      5. (2020) MMWR Morb Mortal Wkly Rep 69(12):343-6 [PubMed]
    4. By Severity
      1. Hospitalized patients with Pneumonia have a 4-15% risk of death
      2. Acute Respiratory Distress Syndrome (ARDS) is associated with 51% mortality
      3. Intubated patients have mortality rates as high as 81%

XXIII. Prevention: General Measures

  1. Social distancing
    1. Keep at least 6 foot (1.8 m) distance between others (greater distance may be required indoors)
  2. Wearing masks (cloth or surgical masks) prevents COVID-19 transmission
    1. Wearing in indoor public spaces helps protect both the wearer and especially those around them
      1. Cloth Mask if asymptomatic
      2. Surgical mask if symptomatic and in healthcare facility
    2. Infectious persons may be contagious days before symptoms manifest
      1. Consider masking in any indoor space including home when virus exposure is possible
      2. Mask should cover both mouth and nose
    3. Consider outdoor masks when social distancing (6 feet) cannot be maintained
    4. Evidence for masking as primary prevention is strong
      1. Brooks (2020) JAMA
        1. https://jamanetwork.com/journals/jama/fullarticle/2768532
      2. Hendrix (2020) MMWR Morb Mortal Wkly Rep 69:930-2 [PubMed]
  3. Surgery
    1. Postpone any non-urgent surgery due to 50% risk of pulmonary complications in first 30 days after diagnosis
      1. (2020) Lancet 396(10243):27-38 +PMID: 32479829 [PubMed]

XXIV. Prevention: Vaccination

  1. Background
    1. Encourage Vaccination in all adult patients (approval in children is pending study as of spring 2021)
    2. All U.S. Vaccines are considered safe and effective and patients should get whichever Vaccine is available
    3. Any of the U.S. Vaccines may be used in immunocompromised patients (none are live virus, no "viral shedding")
    4. The covid Vaccines are safe in pregnancy and Lactation
    5. No Vaccine contains fetal cells (social media myth)
    6. None of the Vaccines are associated with Infertility (social media myth)
    7. (2021) Presc Lett 28(4): 19 [PubMed]
  2. SARS-CoV-2 Viral Vector Vaccines
    1. Johnson/Johnson-Janssen Vaccine (Ad26.Cov2.S)
      1. Uses Adenovirus vector to introduce cellular RNA
        1. Modified viral vector that is considered harmless (not a Live Vaccine)
      2. Single Intramuscular Injection
      3. Compared with mRNA Vaccines, this Vaccine is far more stable
        1. May be stored in refrigerator for months
      4. Efficacy data is difficult to compare with mRNA Vaccines
        1. This Vaccine was tested after emergence of variant strains (e.g. South Africa)
        2. Efficacy: 60-70% overall (much of which was likely variant strains)
        3. Prevents severe Covid19 (ICU admission or death) in 85%
      5. Adverse Effects
        1. Thrombocytopenia
        2. Venous thrombosis (e.g. Cerebral Venous Thrombosis, splanchnic vein thrombosis)
          1. Rare, atypical thrombosis sites
          2. Seen primarily in women age <50 years, 1-2 weeks after Vaccine
          3. May be autoimmune induced condition similar to HIT and TTP
            1. Heparin Induced Thrombocytopenia (HIT)
            2. Thrombotic Thrombocytopenic Purpura (TTP)
      6. References
        1. (2021) Presc Lett 28(3): 13
        2. (2021) Presc Lett 28(5): 25
  3. SARS-CoV-2 mRNA Vaccines
    1. Two mRNA Vaccines (Pfizer, Moderna) released and FDA approved in U.S., December 2020
    2. Expect flu-like symptoms (Fatigue, myalgias), especially after second dose
    3. Both initial U.S. Covid-19 Vaccines are mRNA Vaccines with a unique mechanism
      1. https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/
      2. mRNA is taken up by cells, translated to covid spike protein which is then expelled extracellularly
      3. Antibody forms to COVID-19 spike protein after 2 Vaccine doses spaced 21-28 days apart
      4. The mRNA is fragile and degrades soon after injection, and does NOT affect DNA
    4. Dosing
      1. Pfizer-BioNTech 0.3 ml/dose IM given 21 days apart
        1. Must be diluted with 1.8 ml preservative-free saline
        2. Gently invert Vaccine to mix (do not shake)
      2. Moderna 0.5 ml/dose IM (undiluted) given 28 days apart
        1. Gently swirl Vaccine to mix (do not shake)
    5. Precautions
      1. mRNA Vaccines must be stored at low Temperatures
        1. Pfizer-BioNTech
          1. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/downloads/storage-summary.pdf
          2. Initial: -80ºC to -60ºC (-112ºF to -76ºF)
          3. Up to 2 weeks: -25°C to -15°C (-13°F to 5°F)
          4. Up to 5 days at standard refrigerator Temperature
        2. Moderna
          1. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/downloads/storage-summary.pdf
          2. Initial: -50°C and -15°C (-58°F and 5°F) for unpunctured vials
          3. Up to 30 days: 2° to 8°C (36° to 46°F) for unpunctured vials
          4. Up to 12 hours: 2°F and 25°C (36°F to 77°F) for punctured vials
      2. Avoid other Vaccines within 14 days (to avoid confusion in reactions, and ensure maximal efficacy)
      3. If more than 50% of dose leaks with injection, give a full dose in opposite arm
      4. Second Vaccine dose may be given up to 4 days before recommended schedule and up to 42 days after
        1. However, give second dose even if >42 days from first dose, and repeating series not recommended
    6. Contraindications
      1. Severe Allergic Reaction to Polyethylene glycol, polysorbate or first Covid Vaccine dose
      2. Severe Allergic Reaction to other injectable medications is not an absolute contraindication
        1. Observe for 30 minutes after Vaccination (typically 15 minutes)
        2. Epinephrine injection should be available
      3. Convalescent Plasma or Covid Monoclonal Antibody in last 90 days
        1. Prevents adequate Vaccine immune response
      4. COVID-19 Infection within last 90 days is not a contraindication to Vaccination
        1. However, repeat infection in subsequent 90 days is unlikely (may delay Vaccine)
    7. Efficacy
      1. Both mRNA Vaccines (Pfizer, Moderna) appear to have 95% effectiveness
      2. However, initial efficacy data preceded emergence of more transmissible variant strains
    8. Safety
      1. Appears safe in immunocompromised state, pregnancy, Breastfeeding
      2. Pfizer Vaccine has been FDA approved for age 12 years and older in spring 2021 (adult dosing)
    9. References
      1. (2021) Presc Lett 28(2): 7
  4. Influenza Vaccine (October)
    1. Does not protect against COVID-19, but also does not lower Immune System or make COVID-19 more likely
    2. Patients have been infected with both Influenza and COVID-19 with higher morbidity and mortality
    3. Reduces clinical visits for Influenza
    4. Reduces potential COVID-19 exposures (while seeking healthcare)
    5. Reduces risk of lung injury from Influenza (and possible risk for worse outcome in COVID-19)
    6. Reduces diagnostic confusion in differentiating Influenza presentations from COVID-19 presentations

XXV. Prevention: Transmission

  1. Move patient to airborne infection isolation room or unit with negative airflow
  2. Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing
    1. https://www.youtube.com/watch?v=bG6zISnenPg
    2. Doffing is the highest risk time and should follow a careful protocol (consider assigned staff to help direct)
    3. See Donning and Doffing Personal Protection Equipment
    4. See Personal Protection Equipment
    5. See Respiratory Personal Protective Equipment (includes N95 Mask, PAPR)
  3. Hand Hygiene with soap and water (or >60% Alcohol hand cleanser)
  4. Disinfect surfaces

XXVI. Prevention: Social Isolation Precautions

  1. Social distancing is helps to slow COVID-19 infection spread, but it does have mental health risks
  2. Social distancing is associated with Increased rates of depressed mood, anxiety, Substance Abuse
  3. See Psychological First Aid
  4. Reduce Excessive Worry
    1. Avoid over-checking the news or social media (limit to once or twice daily)
    2. Choose reliable resources for information
  5. Perform regular Exercise
  6. Practice Relaxation Techniques
  7. Stay connected via phone and video conferencing with friends and family
  8. Patient Resources
    1. See Suicide Risk
    2. Disaster Distress Help Line
      1. https://www.redcross.org/get-help/disaster-relief-and-recovery-services/recovering-emotionally.html
  9. References
    1. (2020) Presc Lett 27(5): 25-6

XXVII. Resources

  1. Johns Hopkins Coronavirus Resource Center
    1. https://coronavirus.jhu.edu/
  2. BMJ
    1. https://www.bmj.com/coronavirus
  3. Infectious Disease Society of America (IDSA)
    1. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
  4. National Institutes of Health (NIH)
    1. https://www.covid19treatmentguidelines.nih.gov/
  5. EM:Rap Covid19 Update (March 31)
    1. https://www.youtube.com/watch?v=GLbKyc31XhM
  6. EM:Rap Covid19 Update (March 25)
    1. https://www.youtube.com/watch?v=e51V9M2avrw
  7. CDC COVID-19
    1. https://www.cdc.gov/coronavirus/2019-ncov/index.html
  8. COVID-19 (EM-CRIT: Internet Book of Critical Care)
    1. https://emcrit.org/ibcc/covid19/
  9. Corependium (Mason and Herbert)
    1. https://www.emrap.org/corependium/chapter/rec906m1mD6SRH9np/Novel-Coronavirus-2019-COVID-19

XXVIII. References

  1. (2021) Presc Lett 28(1): 1-3
  2. (2021) Presc Lett 28(5):28
  3. Reuter (2020) Crit Dec Emerg Med, Covid19 Edition, 3-13
  4. Fei Zhou (2020) Lancet , pre-publication online
    1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext
  5. Levitan (2020) ACEP Now
    1. https://www.acepnow.com/article/covid-19-lessons-learned-by-an-emergency-physician-in-new-york-city/
  6. COVID-19 Ventilation: Quick Reference Guide (Bolton Critical Care Team)
    1. https://www.stemlynsblog.org/covid-19-a-primer-on-icu-care-for-the-non-intensivist-st-emlyns/
  7. Nettleton (2021) Am Fam Physician 103(8): 465-72 [PubMed]

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