COVID-19

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See also prevention of COVID-19 transmission in the healthcare setting; COVID-19 (peds); and COVID-19 in pregnancy.

Background

Specific Coronavirus Sub-Types of Clinical Importance


Clinical Features

Initial Presentation

  • Many patients are asymptomatic
  • At onset of symptoms: fever, dry cough, myalgias, fatigue, shortness of breath
    • Fever and cough start early, shortness of breath noted about 9 days into illness
    • Fever not present in all adults
      • Only 1/2 of patients may have fever at time of admission[1]
      • less common in vulnerable populations
    • Less common: cough with sputum, sore throat, headache, congestion, GI symptoms, anosmia, altered mental status
Symptom[2] %
Fever 87.9
Dry cough 67.7
Fatigue 38.1
Sputum production 33.4
Shortness of breath 18.6
Myalgia or arthralgia 14.8
Sore throat 13.9
Headache 13.6
Chills 11.4
Nausea or vomiting 5.0
Nasal congestion 4.8
Diarrhea 3.7
Hemoptysis 0.9
Conjunctivitis 0.8

Common Complications

COVID 19 has a bimodal distribution of disease burden. This initial classic presentation can be followed by delayed and devastating complications. These complications are thought to be the end result of the "cytokine storm" and can occur in an unpredictable fashion.

  • Pulmonary
    • Most common complications: pneumonia, ARDS (average 8 days from onset, 20% of patients in China)
    • Decompensation risk occurs during 2nd week of illness leading to respiratory failure
  • Cardiac Complications[3]
    • Myocarditis,Acute Myocardial infarction, Dysrhythmias, cardiomyopathy, venous thromboembolism.
      • Vasodilatory shock reported in 67% of ICU admissions
      • Cardiomyopathy reported in 33% of ICU admissions
      • Mortality reported 67% of ICU admissions
  • Neurological Complications- thought to be related to the increased levels of interleukin (IL)-6, IL-12, IL-15, and tumor necrosis factor alpha (TNF-α)[4]
    • acute CVA, encephalitis, Guillain-Barré syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis

Differential Diagnosis

Influenza-Like Illness

Causes of Pneumonia

Bacteria

Viral

Fungal

Parasitic

Evaluation

  • Consider minimal workup in well-appearing patients with mild disease

Viral Testing

Testing+Surveillance: COVID

  • RT-PCR (reverse transcriptase polymerase chain reaction) is most commonly used test for confirming cases
    • Sensitivity may be only 75%, but highly specific
    • Turnaround time may be several hours to days
  • Real time RT-PCR e.g. Cepheid
    • Rapid test with results in <1hr
  • Serologic testing for IgM/IgG is not widely available, but likely more sensitive
    • The presence of IgG with a negative RT-PCR likely confirms past exposure and some immunity
  • Test kit availability varies widely by region and institution

Labs

Tests to consider

  • Chemistry
    • BMP
    • Mg
    • Phos
  • CBC w/diff
    • Lymphopenia - common (80%)[5]
    • Thrombocytopenia - common but mild
      • <100 poor prognostic sign [6]
  • Coagulation studies
    • PT/PTT/INR - DIC possible
    • D-dimer, fibrinogen - markers of severity
  • LFTs - mild elevation of ALT/AST
  • Inflammatory Markers
    • CRP - Indicates disease severity [7], [8]
      • Negative points to non-infectious cause (CHF/ESRD)
    • Procalcitonin - normal/mild increased on admission. Normal procalcitonin makes bacterial superinfection less likely.
    • Ferritin
    • LDH
  • Troponin [9] - myocarditis
  • Sepsis labs
    • Lactate
    • Blood culture x2
  • Swabs - Co-infection has been reported as high as 7-20%
    • Flu swab
    • Respiratory viral panel
      • Note that BIOFIRE Respiratory Panel Corona Virus assay does NOT detect this COVID-19 subtype
  • Urine pregnancy test in reproductive-age women
  • Other labs to consider in patients that will be admitted:
    • HBV serologies, HCV antibody
    • Consider (as clinically indicated): PCP DFA, beta-d-glucan, urine legionella Ag, IL-6

Imaging

COVID one pager with links.jpg
COVID one pager with links 2.jpg
Covidcxr.jpg

X-ray

    • Portable CXR preferred in PUI to prevent spread of infection
    • May be normal in early disease
    • Typical pattern is peripheral patchy ground glass opacities (GGO)
    • More opacities correlates with worse disease
    • GGOs may coalesce and appear as infiltrates
    • Not every PUI needs a chest X-ray. Patients who are more likely to need one include any moderate or high acuity patient, elderly, concerning chronic conditions, BMI > 40, high risk socioeconomic situations.

CT

  • Many have normal imaging early on (so CDC DOES not recommend CT for diagnostic purposes at this time)
    • CT (86%) more sensitive than CXR (59%) for detecting GGOs
    • From the American College of Radiology (3/11/20): “Generally, the findings on chest imaging in COVID-19 are not specific, and overlap with other infections, including influenza, H1N1, SARS and MERS. Being in the midst of the current flu season with a much higher prevalence of influenza in the U.S. than COVID-19, further limits the specificity of CT.”

US




Management by Lung Phenotypes

Hypoxemic patients can be divided into two general phenotypes[10]

COVID L Lung Phenotype

  • Characterized by Low elastance (i.e., high compliance), Low ventilation to perfusion ratio, Low lung weight and Low recruitability
  • Often referred to as the “happy hypoxemic”
  • Normal lung volumes and low lung recruitability.
  • Hypoxemia may be due to loss of regulation of perfusion and loss of hypoxic vasoconstriction.
  • These patients can be damaged iatrogenically if you respond to their pulse ox with standard vent modes
  • Do poorly with low tidal volume (TV) and high PEEPs
  • Best managed with high FiO2 which allows you to limit the PEEP
  • Recommended initial vent settings:
    • 8 ml/kg TV, 100% FiO2
    • Increase the PEEP only if the patient is desaturating on a high FiO2.
    • Can turn into COVID H patients on the vent.

COVID H Lung Phenotype

  • Characterized by High elastance, High right-to-left shunt, High lung weight and High recruitability.
  • Increased permeability of the lung leads to edema, atelectasis, decreased gas volume, and decreased TV for a given inspiratory pressure.
  • High degree of lung recruitability.
  • 20 – 30% of patients fit ARDS criteria:
    • Hypoxemia
    • Bilateral infiltrates
    • Decreased the respiratory system compliance
    • Increased lung weight and potential for recruitment
  • The ARDS ladder applies only to this subset of COVID patients.

Management

See prevention of COVID-19 transmission in the healthcare setting for PPE recommendations

COVID-19 PPE Summary Table

Example summary flow chart for determining PPE use














Contact Category Precations Room Type
General (all persons) Social distancing; meticulous hygiene NA
Undifferentiated patients at risk (e.g. prior to evaluation or testing) Contact and droplet precautions including eye protection Negative-pressure NOT required
Persons Under Investigation Contact and droplet precautions including eye protection Negative-pressure NOT required
Aerosol-Generating Procedures Contact and airborn precautions including eye protection Negative-pressure required

Mild Patient Management

  • Isolate all patients suspected of having COVID-19
  • Supportive care is mainstay of therapy for patients with mild viral symptoms
  • 80% of patients do not require hospital admission
  • Discuss with Dept of Public Health, who will guide testing and, if discharging, help patient remain in isolation at home
  • Some define low acuity as SaO2 > 93% on RA, RR < 20, and HR < 110 (if febrile, re-check acuity determined after acetaminophen)
  • Testing+Surveillance: COVID

Moderate/Severe Patient Management

  • Some define moderate and severe acuity as follows:
    • Moderate: SaO2 = 91-93% on RA, RR 20-24, HR 110-124 with wheezing, rales or an otherwise abnormal lung exam.
    • High: SaO2 < 91%, RR > 24, HR > 124.
    • If febrile, treat with acetaminophen and reassess acuity.
  • Cardiovascular [11]
    • Most patients without hemodynamic compromise
    • Maintain euvolemia - hypervolemia may contribute to ARDS
    • Hypoperfusion - cautious fluid resuscitation
    • Vasopressors
  • Infectious disease
    • Acetaminophen for fever
    • Consider empiric Abx for pneumonia
  • Pulmonary [12]
    • Supplemental O2 if Sat<90%
    • "Happy Hypoxemia" Many of these patients will be hypoxic without dyspnea
    • High-flow Nasal Cannula
      • Some guidelines recommending HFNC over BIPAP/CPAP in those that fail low-flow O2. [13]
      • Requires patient to be on airborne isolation.
    • Non-Invasive Ventilation if no HFNC
    • Consider Awake proning to improve oxygenation
    • Bronchodilators if bronchospasm present
      • avoid nebulizers
      • Use Metered-dose inhaler

Respiratory failure

  • NIPPV may increase the spread of viral particles via droplets, making early intubation the preferred airway management strategy in patients with respiratory distress/failure
    • Using 2 viral filters attached to a "2-tube NIPPV circuit" in a negative pressure room may sufficiently prevent viral spread

Intubation of Potential COVID-19 Patients

Aerosol-generating procedure: see this link for PPE recommendations and related precautions

  • Use checklist if available (see example: File:Harbor COVID Airway Management v3-16-20.pdf)
  • Consider use of an Aerolsol Box (Plexiglas box that goes around patient head), if available
  • Use BVM with viral filter or avoid BVM altogether, if possible
  • Use RSI to prevent coughing gagging; consider higher dosing of paralytics.
  • Most experienced provider should perform intubation
  • Upper airway edema may be present leading to difficult intubations
  • Use video laryngoscopy to keep provider face further away from patient (afterwards, clean with grey wipes, observe 3 min wet time)

Lung Protective Mechanical Ventilation

Lung Protective Ventilator Settings[14] should be the default for all intubated patients, unless contraindicated. It has demonstrated mortality benefit for ARDS-like pulmonary conditions; limits barotrauma and decreases complications of high FiO2[15][16]

  1. Mode
    • Volume-assist control
  2. Tidal Volume
    • Start 6-8cc/kg predicted body weight[17]
      • Predicted/"ideal" body weight is used because a person's lung parenchyma does not increase in size as the person gains more weight.
    • Titrate down if peak pressure >30 mmHg
  3. Inspiratory Flow Rate (comfort)
    • More comfortable if higher rather than lower
    • Start at 60-80 LPM
  4. Respiratory Rate (titrate for ventilation)
    • Average patient on ventilator requires 120mL/kg/min for eucapnia
    • Start 16-18 breaths/min
    • Maintain pH = 7.30-7.45
  5. FiO2/PEEP (titrate for oxygenation)
    • Move in tandem to achieve:
    • SpO2 BETWEEN 88-95%
    • PaO2 BETWEEN 55-80

Aerosol-Generating Procedures

Due to higher risk of aerosolizing droplets; infection itself doesn’t seem to be spread via airborne route

Recommended Provider PPE

Contact (including eye protection) and airborne precautions

  • N95 mask or higher-level respirator (e.g. PAPR), plus eye protection, gloves, and gown[18]
    • Consider head coverage: sterile disposable cap with gown or bunny suit
    • Consider two pairs gloves, one under sleeves of gown and one over
    • Consider shoe covers
    • Consider buddy system for donning/doffing
      • If using PAPR, then need pre-assigned RN outside the room to help decontaminate it by wiping it down with purple wipes before you take it off
  • Negative pressure room required, if at all possible
  • Limit personnel in room to only those essential for patient care

Mask Use Technique

  • Mask donning (often incorrectly done):
    • Wash hands BEFORE touching mask
    • Grip mask by loops/bands/ties only
    • Coloured portion typically faces outward
    • Mold / pinch the stiff edge to the shape of your nose
    • Pull the bottom of the mask over your mouth AND chin
    • Make sure you are up to date with fit testing
  • Mask removal:
    • Wash hands BEFORE touching mask
    • Only make contact with the loops/bands/ties. DON’T TOUCH THE MASK ITSELF!

Aerosol-generating procedures list

Avoid these procedures when possible

Intubation of Potential COVID-19 Patients

Aerosol-generating procedure: see this link for PPE recommendations and related precautions

  • Use checklist if available (see example: File:Harbor COVID Airway Management v3-16-20.pdf)
  • Consider use of an Aerolsol Box (Plexiglas box that goes around patient head), if available
  • Use BVM with viral filter or avoid BVM altogether, if possible
  • Use RSI to prevent coughing gagging; consider higher dosing of paralytics.
  • Most experienced provider should perform intubation
  • Upper airway edema may be present leading to difficult intubations
  • Use video laryngoscopy to keep provider face further away from patient (afterwards, clean with grey wipes, observe 3 min wet time)

Investigational Agents

See COVID-19: Medication therapy for the latest recommendations

Generally not started in ED setting; CDC does not recommend for or against any investigational therapies at this time

  • Remdesivir (IV)
    • Consider for severely hypoxemic (Mechanical vent, high PEEP, FiO2 requirements >40%,).
    • Contact Gilead directly for use: compassionateaccess@gilead.com
    • Background: novel antiviral nucleotide analog. Initially developed for Ebola and Marburg (has since been found to show activity against other single stranded RNA viruses such as RSV, Lassa fever virus, Nipah virus and the coronaviruses including MERS and SARS)
      • 3 clinical trials across country (one is NIH adaptive trial)
      • 2 other trials are investigational open-label trials testing different dosages for moderate or severely hospitalized patients
  • Lopinavir/ritonavir
    • anti-retroviral protease inhibitor (old HIV drug combo)
  • Chloroquine, and hydroxychloroquine
    • In vitro activity against SARS-CoV-2, perhaps some anti-inflammatory benefit
  • Azithromycin
    • Macrolide antibiotic (protein synthesis inhibitor)
    • Purported anti-inflammatory mechanisms. Possibly inhibits neutrophil proliferation/lymphocyte activation
  • Glucocorticoids
    • Binds nuclear receptor and regulates gene expression of several inflammatory molecules (e.g. SLPI)
    • May blunt cytokine storm in critically ill patients
    • Caution: also inhibits viral clearance
  • Tocilizumab
    • May blunt cytokine storm in patients with elevated IL-6
  • Convalescent plasma (plasma/antibodies from healthy survivors)
    • Has been used in prior viral epidemics with success
    • No proven benefit, but actively being researched

Contraindicated Therapies

  • Avoid steroids unless strong non-COVID indication (due to progression of viral replication reported from prior coronaviruses; e.g. MERS, SARS)
    • Possible benefit in severely ill patients to treat cytokine storm
  • Avoid nebulizers as they are generally ineffective and may aerosolize virus
    • Albuterol with spacer is safer, though probably ineffective unless co-occuring reactive airway disease
      • MDI equivalents: Albuterol or ipratropium
        • <20 kg or 5yrs old: 4-5 puffs with a spacer every 20 minutes. 4 breaths between puffs.
        • >20 kg or 5yrs old: 8-10 puffs with a spacer every 20 minutes. 4 breaths between puffs.
  • Caution with BiPAP and high-flow nasal oxygen as these may increase viral spread
    • WHO cautiously states that high flow oxygen may be indicated. If used, cover HFNC with surgical mask.
  • There is anecdotal concern about NSAID use; some have suggested preferentially using acetaminophen however, there are no formal recommendations to avoid NSAIDs at this time
  • There is anecdotal concern about ACEi/ARB use, however no formal recommendations to avoid use at this time

Special Situations

Covid-19 and STEMI

  • According to ACC consensus statement "During the COVID-19 pandemic, PCI remains the standard of care for STEMI patients"
  • If thrombolytics are indicated options include:
    • Administer 10u Retavase (reteplase) IV bolus followed by a second bolus at 30 minute rather than PCI. OR
    • Tenecteplase (TNKase) 30 mg IV bolus
    • If Tenecteplase is not available, it is acceptable to administer a lower dose of alteplase (tPA) at 50 mg (8 mg bolus, followed by 42 mg infusion over 90 minutes).
    • Follow thrombolytics by 40u/kg heparin (max dose 4,000 units) IV and 600mg clopidogrel PO and ASA 325 mg PO

Covid-19 and CPR

  • Interim AHA Guidance
    • Don all PPE prior to initiating CPR. CPR is aerosol generating.
    • Intubate early, video laryngoscopy preferred
    • Pause chest compressions during intubation
    • If patient is on ventilator at time of arrest consider leaving patient on ventilator
      • Adjust ventilator to allow for asynchronous ventilation
    • If using BVM then attach high efficiency particulate air (HEPA) filter
    • Use of mechanical compression device (e.g. LUCAS) is encouraged

Disposition

  • Mild cases for persons under investigation for Covid-19 awaiting a positive test result can self quarantine at home in conjunction with the local Public Health Dept
  • "Silent hypoxemia" is now reported in patients with oxygen saturations ranging in the 80s-90s without respiratory distress. Hypoxia is not recommended as an absolute indication for emergent intubation.
    • Note: symptoms may worsen over 2nd week of illness

Admission

  • Hospitalize: Respiratory distress/failure, multi-organ failure, rapid disease progression requiring escalating supportive care. Meets criteria for high acuity above. Moderate acuity with extra risk factors (pneumonia, immunosuppressed, elderly, comorbidities), complicated social situation, worsening symptoms > 10 days out.
    • PSI/PORT, MuLBSTA, and CURB65 scores have all been proposed criteria for admission and predicting outcomes.
  • May consider discontinuation of hospital isolation when:
    • Resolution of fever without anti-pyretic, resolution of symptoms, and negative COVID19 testing

Legal Considerations

Prognosis

COVID-19 Risk Factors for Severe Disease [19]

  • Epidemiological (Catagory 1)
    • Age>55
    • Chronic diseases - Pulmonary, CKD, DM (A1C>7.6%), HTN, CV disease, Obesity
    • Transplant/Immunosuppressed patients
    • Patients taking monoclonal antibodies or biologics
    • HIV (CD4<200 or unknown)
  • Vital signs (Catagory 2)
    • RR>24
    • HR>120
    • SpO2<94 on RA
    • PaO2/FiO2<300mmHg
  • Labs (Catagory 3)
    • D-dimer>1000 ng/mL
    • CPK>2x upper limit
    • CRP>100
    • LDH>245 U/L
    • Elevated Troponin
    • Absolute lymphocyte count <800/mcL
    • Ferritin>500mcg/L

All-Comers

  • Case fatality rate (CFR) = 2-4% (from Hubei data)
    • SARS ~ 10%
    • MERS ~ 35%
    • Seasonal flu ~ 0.1-0.2%
    • 1918 Pandemic Influenza ~ 2-3%

Relation to Age

Case fatality rates by country, age, and percent (%)
Age 80+ 70–79 60–69 50–59 40–49 30–39 20–29 10–19 0–9
China as of 11 February[20] 14.8 8.0 3.6 1.3 0.4 0.2 0.2 0.2 0.0
Italy as of 16 March[21] 19.2 11.8 3.2 1.0 0.3 0.2 0.0 0.0 0.0
South Korea as of 21 March[22] 10.24 6.28 1.52 0.42 0.08 0.11 0.0 0.0 0.0

See Also

External Links

Video

References

  1. 1. Zhou F, Yu T, Du R et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054-1062. doi:10.1016/s0140-6736(20)30566-3
  2. World Health Organization. "Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19)" (PDF): 11–12. Retrieved 5 March 2020.
  3. Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020;38(7):1504-1507. doi:10.1016/j.ajem.2020.04.048
  4. Bridwell R, Long B, Gottlieb M. Neurologic complications of COVID-19. Am J Emerg Med. 2020;38(7):1549.e3-1549.e7. doi:10.1016/j.ajem.2020.05.024
  5. Yang X, Yu Y, Xu J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020. doi:10.1016/s2213-2600(20)30079-5
  6. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020. doi:10.1007/s00134-020-05991-x
  7. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020. doi:10.1007/s00134-020-05991-x
  8. Young B, Ong S, Kalimuddin S et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020. doi:10.1001/jama.2020.3204
  9. https://www.covidprotocols.org
  10. Gattinoni L et al. Covid-19 pneumonia: different respiratory treatment for different phenotypes. Intensive Care Medicine. 2020. https://www.esicm.org/wp-content/uploads/2020/04/684_author-proof.pdf
  11. Alhazzani W, Møller M, Arabi Y et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020. doi:10.1007/s00134-020-06022-5
  12. Alhazzani W, Møller M, Arabi Y et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020. doi:10.1007/s00134-020-06022-5
  13. Alhazzani W, Møller M, Arabi Y et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020. doi:10.1007/s00134-020-06022-5
  14. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308.
  15. ARDSnet
  16. O'Brien J. Absorption Atelectasis: Incidence and Clinical Implications. AANA Journal. June 2013. Vol. 81, No. 3.
  17. Brower RG, et al. "Ventilation With Lower Tidal Volumes As Compared With Traditional Tidal Volumes For Acute Lung Injury And The Acute Respiratory Distress Syndrome". The New England Journal of Medicine. 2000. 342(18):1301-1308.
  18. https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.html#take_precautions
  19. Massachusetts General Hospital COVID-19 Treatment Guide Version 1.36 04/05/2020. https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf. Published 2020. Accessed April 8, 2020.
  20. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (17 February 2020). "The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020". China CDC Weekly. 2 (8): 113–122. Retrieved 18 March 2020.
  21. Epidemia COVID-19. Aggiornamento nazionale 16 marzo 2020" (PDF) (in Italian). Rome: Istituto Superiore di Sanità. 16 March 2020. Retrieved 18 March 2020.
  22. "코로나바이러스감염증-19 국내 발생 현황 (3월 21일, 정례브리핑)". Korea Centers for Disease Control and Prevention. 21 March 2020. Retrieved 21 March 2020.