II. Epidemiology

  1. Corona virus that originated in bats (similar to SARS, MERS)
  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. Pathophysiology: General

  1. Incubation: 4 to 7 days (mean 5 days)
  2. Person to person transmission with viral shedding 17-24 days (median 20 days) in China survivors

IV. 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. Inflammatory cytokines cause tissue damage with Pneumonia and ARDS

V. Findings: Signs and Symptoms

  1. General and prodromal
    1. Fever (44% at initial presentation, 83-98% on hospitalization)
    2. Myalgia
    3. Fatigue
  2. Upper Respiratory
    1. Pharyngitis
  3. Cardiopulmonary
    1. Cough (46-82%)
      1. Hemoptysis may occur
      2. Variably productive cough
    2. Shortness of Breath (31%)
    3. Hypoxia
      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
    2. Palpitations
  5. Gastrointestinal
    1. Diarrhea
  6. Neurologic
    1. Headache
    2. Loss of Smell Sensation (Anosmia)
    3. Altered Taste Sensation (Dysgeusia)
    4. Confusion or Altered Level of Consciousness (encephalopathy)
  7. Skin
    1. Pernio-like reactions of distal digits with erythema and swelling ("Covid Toes")
    2. Acrocyanosis
    3. Livedo Reticularis

VI. Labs

  1. COVID-19 Diagnosis (efficacy varies widely by test version, technique, timing)
    1. PCR for Corona Virus 2019
      1. Nasopharyngeal and Oropharyngeal swab
    2. Antibody Testing for Corona Virus 2019
      1. Unclear how long Antibody confers immunity (may be short as with seasonal Influenza)
  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)
      1. Lymphopenia is most common (63%)
      2. Leukocytosis (24-30%)
    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
  5. Markers of increased mortality
    1. D-Dimer (increased >1)
      1. Not routinely recommended unless suspicion for Pulmonary Embolism
    2. Troponin Increased
  6. Other testing
    1. Blood Cultures (draw and hold first set with initial lab testing)

VII. 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

VIII. Complications

  1. Precautions
    1. Complications and decompensation are more common after 7 days of illness
  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. Kawasaki Disease
    1. Jones (2020) Hosp Pediatr +PMID:32265235 [PubMed]

IX. Management

  1. Prevent 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
  2. Supportive care
    1. See ABC Management
    2. See Intensive Care
    3. See Pneumonia Management
    4. See ARDS Management
    5. Avoid aggressive fluid Resuscitation (do NOT use Sepsis level 30 cc/kg)
    6. Have Norepinephrine available for Hypotension
  3. Bronchodilators
    1. Avoid nebulizer use due to dispersion of virus
    2. Albuterol HFA Inhaler as needed
  4. Corticosteroids
    1. Avoid Corticosteroids early in course (risk of increased viral shedding, worse outcomes)
    2. May consider Methylprednisolone 60 mg IV daily for 3-6 days in severe ARDS, intubated with immunopathologic response
    3. May also use Corticosteroids in those with Exacerbation of Asthma or COPD
  5. Oxygenation
    1. Oxygen by Nasal Cannula to maintain Oxygen Saturation 92-96%
    2. Oxygen requirement >5-6 liters/min should prompt move to HHFNC, CPAP or Endotracheal Intubation
    3. Consider awake prone position (direct patient to roll to prone position for as long as they are comfortable)
  6. Non-Invasive Positive Pressure Ventilation
    1. Use all devices with viral filter (HEPA filter)
    2. High Flow Nasal Cannula (up to 30 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 much 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
  7. Endotracheal Intubation
    1. Precautions
      1. Although early intubation has been favored, CPAP despite Hypoxia may be preferred in some patients
      2. Endotracheal Intubation is among the highest risk procedures for transmission
      3. 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)
      4. Have rescue airway at bedside
        1. Attach 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)
    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
      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. Rapid Sequence Intubation
      1. Ketamine and Rocuronium is the a common sedative and paralytic combination used in these intubations
    7. Preoxygenation
      1. Preoxygenation for 5 minutes without Positive Pressure Ventilation
      2. 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
        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
    9. Mechanical Ventilator settings
      1. Follow ARDSnet protocols
      2. Use low Tidal Volumes (e.g. 6 cc/kg Ideal Body Weight)
      3. Use high Respiratory Rates (e.g. 20/min)
      4. May start with high FIO2 but rapidly decrease FIO2 while increasing PEEP
      5. Typical starting PEEP may approach 10
  8. Specific measures under investigation
    1. Convalescent Plasma
      1. Shen (2020) JAMA +PMID:32219428 [PubMed]
    2. Remdesivir
      1. Viral RNA Polymerase Inhibitor that may speed COVID-19 Recovery, but does unclear if affects mortality
      2. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
      3. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
    3. Tocilizumab
      1. Anti-IL6 Monoclonal Antibody used in cancer treatment being 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
  9. 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
  10. 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
  11. 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
  12. Indications for empiric Community Acquired Pneumonia treatment
    1. Imaging consistent with Pneumonia
    2. Procalcitonin >0.26 ng/ml

X. Disposition

XI. Prognosis

  1. Indicators of 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)
    4. Immunocompromised patients
    5. Pregnancy
    6. D-Dimer >1 on admission
    7. SOFA Score high
  2. Mortality
    1. Hospitalized patients with Pneumonia have a 4-15% risk of death

XII. Prevention: Video Resources

  1. Stay at Home, Stop the Spread Video (EM:RAP)
    1. https://www.youtube.com/watch?v=Y7PMvJJztAA
  2. We're Here to Help (EM:Rap)
    1. https://www.youtube.com/watch?v=0Omxx75I8C0

XIII. 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

XV. References

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