II. Epidemiology
- Corona virus that originated in bats (similar to SARS, MERS)
- Enveloped, single-stranded RNA novel coronavirus
- Originally acquired at seafood and live animal market in Wuhan, Hubei Province, China in late 2019
- Initial International hot-spots (Feb 2020): China, Iran, Northern Italy, South Korea, Japan
- Initial U.S. hot spots (Feb 2020): Washington and California (sporadic cases in other regions)
III. Risk Factors: High Risk Patients for Serious Complications (criteria for emergency use Covid medications)
- Body Mass Index (BMI) >=35
- Chronic Kidney Disease
- Diabetes Mellitus
- Immunocompromised Condition
- Current use of immunosuppressant
- Age >=65 years old
- Age >= 55 years old AND Comorbidity
- Cardiovascular Disease
- Hypertension
- Chronic Obstructive Pulmonary Disease (or other chronic respiratory disease)
- Children 12 to 17 years old with at least one of the following risk factors
- Body Mass Index (BMI) >= 85th percentile by age and gender
- Sickle Cell Disease
- Congenital or acquired heart disease
- Neurodevelopmental disorders (e.g. Cerebral Palsy)
- Medically related device dependence (e.g. Gastrostomy, Tracheostomy, non-covid related NIPPV)
- Asthma, reactive airway disease or other chronic respiratory disease requiring daily medication for control
IV. Pathophysiology: Infectivity
- Person to person transmission with viral shedding 17-24 days (median 20 days) in China survivors
- Infectious 5 to 13 days after symptom resolution
-
Infectivity (R0, pronounced "R-Naught")
- R0 appears to be 2-3 in most cases of Corona Virus 19
- However, there have been "super spreader" cases in which R0>20 (e.g. large gatherings)
- R0 appears to be 2-3 in most cases of Corona Virus 19
V. Pathophysiology: Severe Course Timing
- Incubation: 4 to 7 days (mean 5 days, some cases as long as 12-14 days)
- Day 0: First Symptoms (see below)
- Day 5: Dyspnea
- Day 7: Hospital Admission
- Day 8: Acute Respiratory Distress Syndrome (ARDS)
- Day 12-18: Death
- Day 22: Survivor hospital discharge
- Day 30: Recovery in mild cases (although Anosmia may persist for months)
- Day 60-75: Recovery in severe cases
VI. Pathophysiology: Illness stages
- Replication Stage
- Virus replicates with relatively minor symptoms
- Immunologic Response Stage
- Immune response after the first few days to week is a normal adaptive response in 80% of patients
- Exaggerated immunopathologic response (Cytokine Storm) occurs in <20% of cases
- See Cytokine Release Syndrome (Cytokine Storm)
- Inflammatory Cytokines cause tissue damage with Pneumonia and ARDS
VII. Findings: Signs and Symptoms in Adults
- General and prodromal
- Upper Respiratory
- Pharyngitis (5-14%)
- Nasal congestion or Rhinorrhea (2 to 5%)
- Conjunctivitis (1%)
- Cardiopulmonary
- Cough (46-82%)
- Hemoptysis (1-2%)
- Cough is typically dry (but may be productive in up to one third of cases)
- Shortness of Breath (31%)
- Associated with more severe disease
- Hypoxia (9% of mild cases, 40% of severe cases)
- Cough (46-82%)
- Cardiac
- Chest tightness, pain or pressure (2 to15%)
- Palpitations
- Gastrointestinal
- Neurologic
- Headache (3-14%)
- Confusion or Altered Level of Consciousness (encephalopathy)
- Dizziness (8%)
- Altered taste or smell (34-64% of patients)
- Loss of Smell Sensation (Anosmia)
- Altered Taste Sensation (Dysgeusia)
- Skin
- Rash (up to 20% of cases)
- Pernio-like reactions of distal digits with erythema and swelling ("Covid Toes")
- Acrocyanosis
- Livedo Reticularis
VIII. Findings: Signs and Symptoms in Children
IX. Precautions: Red Flag Findings Prompting Emergent Evaluation (Triage Protocols, return indications)
-
Vital Signs
- Heart Rate >110
- Respiratory Rate >22
- Oxygen Saturation <93%
- Systolic Blood Pressure <100 mmHg
- Minimal to no Urine Output
- Cardiopulmonary
- Hemoptysis
- Severe Chest Pain or pressure
- Severe Shortness of Breath at rest
- Skin
- Cyanosis
- Cold, clammy, pale or mottled skin
- Non-blanching rash
- Mental status
- Lethargy or difficult to arouse
- New confusion
X. Labs
- COVID-19 Diagnosis (efficacy varies widely by test version, technique, timing)
- Indications for COVID-19 Testing (Antigen or PCR)
- Symptomatic patients
- Asymptomatic patients undergoing hospitalization or procedures
- Asymptomatic patients with known positive exposure >15 min (esp. indoors without mask or social distancing)
- Avoid testing within first 48 hours (high False Negative Rate)
- Consider testing at 3-5 days and 7-10 days after exposure
- Quarantine for 14 days after significant exposure regardless of test results
- No need to re-test patients after positive test (use 10 day quarantine guidelines below)
- Tests may remain positive for weeks
- Re-exposed patients after positive COVID-19 Test need not be re-tested within first 3 months
- Persistent positive tests may confuse results and Immunity is likely for at least 3 months
- (2020) Presc Lett 27(10): 55
- PCR for Corona Virus 2019 (preferred)
- Obtained via Nasopharyngeal swab (deep nasal swab) or Oropharyngeal swab
- Test accuracy depends on an adequate swab sample
- FDA approved PCR tests should have Test Sensitivity >95%, Test Specificity 100%
- Antigen Tests for Corona Virus 2019
- Obtained via Nasopharyngeal swab (deep nasal swab) or Oropharyngeal swab
- Fast and inexpensive tests similar to Rapid Strep Test and Rapid Influenza Test (but lower efficacy than PCR)
- Lower Test Sensitivity: 70-80%
- Antibody Testing (IgG and IgM) for Corona Virus 2019
- Unclear if Antibody confers Immunity
- Unclear how long Antibody confers Immunity (may be short as with seasonal Influenza)
- FDA approved Antibody tests should have Test Sensitivity >90% and Test Specificity >95%
- High False Positive Rate (20-30%) in low disease Prevalence regions (much of U.S. in Fall 2020)
- Consider testing patients with repeatedly negative Antigen tests, but persistent symptoms for weeks
- Indications for COVID-19 Testing (Antigen or PCR)
- Differential Diagnosis Evaluation
- Influenza nasopharyngeal swab
- Coninfection with Influenza is unlikely but possible (may occur in 5% of cases)
- Respiratory Virus Panel
- Typically includes Influenza, parainfluenza, RSV, Metapneumovirus, Rhinovirus, Adenovirus
- Pertussis PCR
- Streptococcal Pneumoniae urine Antigen
- Legionella urine Antigen
- Influenza nasopharyngeal swab
- Other lab findings
- Complete Blood Count (CBC) with Platelet Count
- Lymphopenia (Lymphocytes <1500/mm3) is most common (63%)
- More common in worse disease (present in >80% of those hospitalized)
- Leukocytosis (24-30%)
- Thrombocytopenia (associated with worse prognosis)
- Lymphopenia (Lymphocytes <1500/mm3) is most common (63%)
- Liver Function Test
- Liver transaminases (AST, ALT) mildly increased (37%)
- Lactate Dehydrogenase
- Venous Blood Gas
- Serum Lactate
- Complete Blood Count (CBC) with Platelet Count
- Acute phase reactants
- C-Reactive Protein
- Serum Ferritin
- Procalcitonin
- Normal on presentation
- Increase may suggest Bacterial Infection or severe Covid19 infection
- Markers of increased mortality
- D-Dimer (increased >1)
- D-Dimer >1.5 mcg/ml may prompt prophylactic Anticoagulation at some facilities
- Serum Troponin Increased
- Lymphopenia (Lymphocytes <1500/mm3)
- Interleukin-6 (IL-6) Increased
- Liver Function Test increases (AST, ALT, LDH, PT/INR increased)
- Serum Creatinine increased
- Creatine Kinase (CK) increased
- Serum Ferritin increased
- Procalcitonin Increased
- D-Dimer (increased >1)
- Other testing
- Blood Cultures (draw and hold first set with initial lab testing)
XI. Imaging
-
Chest XRay
- Bilateral infiltrates
-
Chest CT
- Bilateral regions of lung consolidation and ground glass opacities
- Progression from scattered ground glass findings to coalescence and then lung consolidation in the most severe cases
-
Lung Ultrasound
- Survey the lungs using a systematic "lawn mower" approach
- Ultrasound B-Line artifacts correlate with CT ground glass findings
- Progression from scattered b-line artifacts to b-line coalescence and then lung consolidation (liver-like appearance)
- https://emcrit.org/ibcc/COVID19/#lung_ultrasonography
XII. Differential Diagnosis
- See Hypoxia
- See Dyspnea
-
Bacterial Infections
- Streptococcal Pneumoniae
- Pertussis
- Legionella pneumonia
- Streptococcal Pharyngitis
- Opportunistic lung infection
- Viral Respiratory Infections
- Influenza
- Parainfluenza
- Metapneumovirus
- Rhinovirus
- Adenovirus
- Non-Infectious Causes
XIII. Complications
- Precautions
- Complications and decompensation are more common after 7 days of illness
- Prolonged symptoms (>14-21 days) in up to 35% of cases
- Respiratory Effects
- Multi-lobar Pneumonia
- Acute Respiratory Distress Syndrome (ARDS)
- Cardiac effects
- Myocarditis (Cardiomyopathy with Cardiogenic Shock)
- May mimic Acute Coronary Syndrome (findings on EKG may be identical to STEMI)
- Acute Coronary Syndrome
- Like Influenza, COVID-19 creates a severe inflammatory response that precipitates Plaque rupture and MI
- Cardiology is unlikely to perform PCI on active COVID-19 patients
- May need to consider MI Thrombolysis (however, high risk in patients at risk of DIC)
- Myocarditis (Cardiomyopathy with Cardiogenic Shock)
- Thrombosis
- Venous Thromboembolism
- Mycocardial Infarction
- Cerebrovascular Accident
- Skin microthrombi such as Pernio (see dematologic findings as above)
- https://www.sciencedirect.com/science/article/pii/S0049384820301201
- Encephalopathy
-
Multisystem Inflammatory Syndrome (similar to Kawasaki Disease)
- Prolonged Fever, severe illness and multiorgan involvement
- Jones (2020) Hosp Pediatr +PMID:32265235 [PubMed]
- Acute Renal Failure
XIV. Management: General Measures
- See Prevention below
- Includes Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing
-
TeleHealth triage protocol
- Mild symptoms
- COVID testing
- Self-care (e.g. deep breathing Exercises and position changes - see below)
- Quarantine (see below)
- Monitor symptoms, signs and oyxgen saturation probe (if available) and return if consistently <92%
- Telephone Follow-up
- Moderate Symptoms
- Outpatient, in-person visit
- Severe Symptoms (esp. with comorbidities) or Red Flags (see above)
- Emergency Department evaluation
- Mild symptoms
- Position Changes
- Consider awake prone position (as well as on their left and right lateral decubitus positions, and sitting upright)
- Direct patient to roll to prone position and other positions for as long as they are comfortable
- Proning obese patients may be difficult
- Consider pregnancy massage mattress
- https://prone2help.org
- Practice deep breathing Exercises
- Disposition: Home Recommendations
- High Risk Patients (see Risk Factors Above)
- Monoclonal Antibodies (see below)
- Practice position changes and deep breath Exercises (see above)
- Monitor for Hypoxia (with portable Oxygen Saturation monitor)
- Return for Oxygen Saturations <92%
- Duration of home quarantine recommendations
- Asymptomatic contacts
- Quarantine for 14 days after last exposure
- Monitor for fever and possible COVID-related symptoms daily
- Symptomatic patients or positive COVID test
- Quarantine >= 10 days and no fever for at least 1 day (was 3 days) AND improving symptoms (e.g. cough)
- Quarantine for at least 20 days if severely immunocompromised
- Isolate within home, staying in sick area/room away from others and without sharing bathroom
- Quarantine >= 10 days and no fever for at least 1 day (was 3 days) AND improving symptoms (e.g. cough)
- https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html
- Asymptomatic contacts
- High Risk Patients (see Risk Factors Above)
XV. Management: Emergency Department Overall Approach
- See ABC Management
- See Intensive Care
- See Pneumonia Management
- See ARDS Management
- Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing - see below
- Avoid aggressive fluid Resuscitation (do NOT use Sepsis level 30 cc/kg)
- Have Norepinephrine available for Hypotension
XVI. Management: Oxygenation
- Precautions
- Oxygenation combined with position changes (see above) are the two most critical interventions
- Monitor oxygenation and ventilation closely and recheck patient every 1-2 hours (patient decompensate quickly)
- Review work of breathing, Respiratory Rate, Heart Rate, Oxygen Saturation, Capnography and other parameters
- Consider Endotracheal Intubation in those tiring, failing oxygenation strategies
- Oxygenation by Nasal Cannula and Mask
- Oxygen by Nasal Cannula up to 5-6 L/min (humidified if available) to maintain Oxygen Saturation 92-96%
- Persistent Hypoxia despite Nasal Cannula up to 5-6 L/min
- Non-rebreather at 15 L/min may be applied over the top of the Nasal Cannula
- Helps prevent aerosolization
- Allows for adequate oxygenation for severe Hypoxia
- Levitan (2020) ACEP Now (see link below)
- Non-Invasive Positive Pressure Ventilation (esp. HHFNC, or in some cases non-vented CPAP)
- Endotracheal Intubation
- Non-rebreather at 15 L/min may be applied over the top of the Nasal Cannula
-
Non-Invasive Positive Pressure Ventilation (NIPPV)
- Use all devices with viral filter (HEPA filter)
- High Flow Nasal Cannula (typically 40 to 60 L/min)
- Appears safer than BiPAP, CPAP without significant viral dispersion
- Allows for the oxygenation and increased alveolar recruitment that many with corona virus require
- However, anecdotally at high volume sites, High Flow Nasal Cannula appears less effective than CPAP
- CPAP
- BIPAP is not recommended
- CPAP alone appears adequate to overcome Atelectasis and surfactant loss
- BiPAP appears to add little benefit in Covid19 over CPAP, with the risk of virus dispersion
XVII. Management: Endotracheal Intubation
- Precautions
- Although early intubation has been favored, NIPPV despite Hypoxia may be preferred in some patients
- Endotracheal Intubation is among the highest risk procedures for transmission
- COVID-19 patients are intubated on Mechanical Ventilation for on average 10 days
- See Mechanical Ventilation for potential complications
- Mortality of intubated patients ranges from 20-90%
- COVID-19 patients are difficult intubations (most experienced intubating clinician should perform)
- Rapid desaturation despite Apneic Oxygenation
- Signficant airway edema of the supraglottic region that distorts landmarks
- Elastic Bougie has been less helpful in these patients (not firm enough given edema)
- Maximize Endotracheal Tube first pass success
- Slow down and expect desaturation with intubation
- Exercise caution in Laryngoscope introduction, rotating around the Tongue
- Use the Levitan technique of gradual exposure of the uvula, epiglottis, aryepiglottic fold, Larynx
- Avoid Awake Nasotracheal Intubation
- Higher risk of aerosolization
- Nasal Intubation duration limit of 3 days is too short for COVID-19 patients
- Have rescue airway at bedside
- Attach I-Gel or LMA with HEPA Filter to ambubag with PEEP Valve
- Early intubation has been advocated over NIPPV (other than High Flow Nasal Cannula) for less viral transmission
- However, intubation puts healthcare staff at significant transmission risk
- Ventilators are a limited resource (Italian providers placed up to 4 patients on the same Ventilator)
- Have a lower threshold for intubation when failing High Flow Nasal Cannula
- COVID-19 patients may give less warning (Hypoxemia without increased resp. effort) before rapid decompensation
- Rising FIO2 requirements (>75% FIO2) and high Respiratory Rate >26/min
-
Personal Protection Equipment (PPE)
- See Donning and Doffing Personal Protection Equipment
- Providers are using Powered Air Purifying Respirator (PAPR) for intubation where available
- Surgical hat and gown
- N95 Mask beneath a surgical mask with Face Shield
- Ideally uses a full Face Shield or goggles
- Double gloves
- Intubation Equipment
- Video Laryngoscopy is preferred (allows for distance from airway) over Direct Laryngoscopy
- However, supraglottic inflammation or restricted mouth opening may require Direct Laryngoscope backup
- Consider Macintosh-Shaped Video Laryngoscopy blades (may also be used with Elastic Bougie)
- Endotracheal Tube with stylet and 10 cc syringe
- HEPA Filter
- CO2 Detector
- Dirty equipment bucket at feet of intubating provider
- Rescue Airway (e.g. I-Gel or LMA with HEPA Filter)
- Preoxygenation equipment (see below)
- Bag-Valve Mask (BVM) with PEEP Valve
- EtCO2 adapter (inline between Bag and Mask)
- Oxygen tubing attached and oxygen flow set at 6 L/min
- Viral Filter (inline between Bag and Mask)
- Mask
- Use NIPPV mask if available for better seal
- Video Laryngoscopy is preferred (allows for distance from airway) over Direct Laryngoscopy
-
Rapid Sequence Intubation (with K-ROC)
- Ketamine and Rocuronium is the a common Sedative and paralytic combination used in these intubations
- Ketamine 1.5 to 2 mg/kg
- Rocuronium 1.5 to 2 mg/kg
- Preoxygenation
- Preoxygenation for 5 minutes without Positive Pressure Ventilation
- Continue Apneic Oxygenation throughout intubation, despite with expect rapid oxygen desaturation
- Use Rapid Sequence Intubation with Apneic Oxygenation, but avoid PPV (Bag Valve Mask or Bipap)
- However, Scott Weingart, MD has an innovative approach to safe preoxygenation with CPAP
- https://emcrit.org/emcrit/covid19-intubation-packs-and-preoxygenation-for-intubation/
- Safe PPE Procedure after passing Endotracheal Tube
- Inflate ET Tube cuff and dispose of syringe
- Drop stylet and Laryngoscope Blade into the dirty equipment bucket
- Place Laryngoscope Handle onto work surface now considered dirty
- Remove outer gloves
- Attach HEPA Filter to ET Tube (will remain in place throughout Mechanical Ventilation period)
- Attach CO2 detector and ambubag to confirm color change
- Remove only the CO2 detector (leave HEPA Filter in place) and continue ventilation
- Carefully evaluate ET Tube Depth (CXR may be delayed)
- Mechanical Ventilator settings
- See Mechanical Ventilation
- Follow ARDSnet protocols
- Initial Setting
- Use low Tidal Volumes (e.g. 6 ml/kg Ideal Body Weight)
- Use high Respiratory Rates (e.g. 20/min)
- However monitor closely for Breath Stacking (Auto-PEEP)
- Monitor for Hypotension (decreased Preload)
- May start with high FIO2 but rapidly decrease FIO2 while increasing PEEP
- See PEEP Table
- Goal Oxygen Saturation 92 to 96%
- FIO2 <0.4, Start with PEEP 5 cmH2O
- Consider Ventilator Weaning if stable on low FIO2 and low PEEP (see below)
- FIO2 0.4 to 0.6, Start with PEEP 10 cmH2O
- See Ventilator Troubleshooting (evaluate for mucous plugging, Pneumothorax, VAP)
- FIO2 >0.6, Start with PEEP 15 cmH2O
- Inspiratory to Expiratory Ratio (I:E) to 1:2 or 1:1.5
- Consider a lung recruitment maneuver at start of Mechanical Ventilation
- Increase Tidal Volume to 8-10 ml/kg for 10 minutes and then return to 6 ml/kg OR
- Increase pressure to 30 cm H2O for 30 seconds
- Ventilator Weaning
- Consider when FIO2 <0.5 and PEEP <10 cmH2O
- Decrease sedation and trial pressure support
- Monitoring
- Permissive hypercapnea, but keep pH >7.2 (permissive hypercapnea)
- Plateau pressure <30 cm H2O
- Follow ABG every 12 hours (and as needed for clinical worsening)
- Inadequate Ventilators available
-
Post-Intubation Sedation and Analgesia
- Inadequate sedation risks Post-Traumatic Stress Disorder
- Expect to use higher doses of sedation
- Patients have Respiratory Failure, but intact mentation
- Plan to sedate to RASS -3 to -5 (Deep Sedation )
- Start with Propofol and Fentanyl
- Add Dexmedetomidine or Midazolam
XVIII. Management: Lines and Fluids
- Left Internal Jugular Central Line
- Reserve right internal jugular for ECMO
- Arterial Line
- Nasogastric Tube or Orogastric Tube
- Urinary Catheter
- Maintain negative flud balance
- Avoid maintenance Intravenous Fluids
- Supply fluids through enteral feedings and the fluid in delivered medications
- Consider IV Furosemide (lasix) 20 mg every 8 hours
- If fluid bolus is required, use 20% Human Albumin
- Enteral Feedings (Nasogastric Tube)
- Use calorie dense feedings, targeting 25 kcal/kg/day
- Use senna 15 ml twice daily to promote regular stooling once enteral feeds are established
- Consider adding Lactulose
XIX. Management: Adjunctive Measures
- Bronchodilators
-
Corticosteroids
- Dexamethasone
- Indicated in COVID-19 Patients on Supplemental Oxygen or Mechanical Ventilation
- Dosing: Dexamethasone 6 mg daily for up to 10 days
- https://www.covid19treatmentguidelines.nih.gov/dexamethasone/
- Horby (2020) N Engl J Med +PMID:32678530 [PubMed]
- Other Corticosteroid indications
- May also use Corticosteroids in those with Asthma Exacerbation or COPD exacerbation
- Intensivists have also used Methylprednisolone 60 mg IV daily for 3-6 days in severe ARDS
- Corticosteroids are not recommended early in COVID-19 course for those not with indications above
- Risk of increased viral shedding, worse outcomes
- Dexamethasone
- Specific measures under investigation
- Monoclonal Antibodies
- Among the most promising COVID-19 treatments as of December 2020
- Monoclonal Antibody helps prevent SARS-CoV-2 from entering the cell
- FDA Emergency Use Indications (none are FDA approved for routine use in December 2020)
- Confirmed positive COVID-19 testing AND
- High Risk Patients for Serious Complications (see Risk Factors as above) AND
- Patient NOT hospitalized for COVID-19 AND
- Patient not requiring Supplemental Oxygen for COVID-19
- No increase in Supplemental Oxygen if chronic use (e.g. oxygen dependent COPD)
- Preparations (Outpatient Infusions)
- General
- Age>=12 years old AND weight >=40 kg
- Recommended as soon as possible (within 10 days of symptom onset)
- Rare Hypersensitivity Reactions have occurred
- As of January 2021, many insurers in U.S. are covering doses
- Defer Covid-19 Vaccination for at least 90 days after Monoclonal Antibody dose
- These monoclonal antibodies may interfere with Vaccine immune response
- Combination Casirivimab and Imdevimab (Regeneron product)
- Casirivimab 1200 mg and Imdevimab 1200 mg infused over 1 hour
- https://www.covid19treatmentguidelines.nih.gov/statement-on-casirivimab-plus-imdevimab-eua/
- Bamlanivimab (Lilly product)
- Bamlanivimab 700 mg infused over 1 hour
- https://www.covid19treatmentguidelines.nih.gov/statement-on-bamlanivimab-eua/
- General
- Among the most promising COVID-19 treatments as of December 2020
- Convalescent Plasma
- Remdesivir
- Viral RNA Polymerase Inhibitor (nucleotide analog prodrug) that inhibits viral RNA synthesis
- Originally developed for use in Ebola
- May speed COVID-19 Recovery, but unclear if affects mortality
- Indicated in moderate Covid with Hypoxia, bilateral lung involvement, or severe cases
- Dosing: 200 mg IV (or 10/mg/kg) for 4-9 days
- https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
- https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
- Viral RNA Polymerase Inhibitor (nucleotide analog prodrug) that inhibits viral RNA synthesis
- Tocilizumab
- Anti-IL6 Monoclonal Antibody used in Cytokine Release Syndrome
- Studied in COVID-19 as of March 2020 (phase 3 trial)
- https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia
- Monoclonal Antibodies
- Specific measures that do not appear effective (or for which risk is worse than benefit)
- Chloroquine or Hydroxychloroquine
- Mortality may be higher (low efficacy, adverse effects) with these drugs despite promising results in early studies
- Chloroquine and Hydroxychloroquine have numerous adverse effects (e.g. QTc Prolongation)
- https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2
- https://wattsupwiththat.com/2020/03/17/an-effective-treatment-for-coronavirus-covid-19-has-been-found-in-a-common-anti-malarial-drug/
- Azithromycin
- Results as of May 2020 are not promising
- Initial trials combined with Chloroquine showed possible improved outcomes
- However, there is risk of Ventricular Arrhythmia related to QTc Prolongation with this combination
- Lopinavir/Ritonavir (Kaletra, LPV/r)
- As of May 2020 studies demonstrate no significant efficacy, and risk of Drug Interactions
- Was initially considered when Chloroquine was not available
- Young (2020) JAMA
- https://jamanetwork.com/journals/jama/fullarticle/2762688
- Chloroquine or Hydroxychloroquine
- Other measures that have been used with poor evidence
- Medications with unclear risk
- NSAIDs
- Early in COVID-19 course, some postulated risk of NSAIDs, but no current evidence of risk as of May 2020
- Use Acetaminophen as a first-line Analgesic, but NSAIDs are not currently contraindicated in COVID-19
- ACE Inhibitors and Angiotensin Receptor Blockers (ARBs)
- Coronavirus targets ACE-2 Receptors as an entry into cell
- Postulated that ACE Inhibitors might up-regulate ACE Receptors
- No evidence as of significant benefit or harm of these agents as of May 2020
- NSAIDs
- Indications for empiric Community Acquired Pneumonia treatment
- Imaging consistent with Pneumonia
- Procalcitonin >0.26 ng/ml
XX. Prognosis: Severe Cases
- Severe disease in 14% of patients
- ICU admission in 5% of adults and 2% of children
- Risks for complications or more serious, progressive infection or death
- Male gender
- Older age (60 years and older)
- Comorbidity (e.g. Hypertension, Diabetes Mellitus, Cardiovascular Disease, Renal Disease, Liver Disease, COPD)
- Hospitalized patients: 23 to 71% have at least one comorbid condition
- ICU Patients: 43 to 78% have at least one comorbid condition
- Mortality: >94% have at least one comorbid condition
- Body Mass Index (BMI>30)
- Obstructive Sleep Apnea
- Tobacco Abuse
- Smoking confers more severe case (RR 1.4)
- Smoking confers increased risk of ICU admission, Mechanical Ventilation and death (RR 2.4)
- Vardavas (2020) Tob Induc Dis 18:20 [PubMed]
- Immunocompromised patients (e.g. HIV, Autoimmune Disease, cancer, immunosuppressants)
- Pregnancy (or first 2 weeks postpartum)
- Sickle Cell Anemia
- D-Dimer >1 on admission
- SOFA Score high
- Age-Related Prognosis
- Age <20 years
- Hospitalizations: 1.6 to 2.5%
- ICU admissions: 0
- Deaths: 0
- Age 20-44 years
- Hospitalizations: 14.3 to 20.8%
- ICU admissions: 2.0 to 4.2%
- Deaths: 0.1 to 0.2%
- Age 45 to 54 years
- Hospitalizations: 21.2 to 28.3%
- ICU admissions: 5.4 to 10.4%
- Deaths: 0.5 to 0.8%
- Age 55 to 64 years
- Hospitalizations: 20.5 to 30.1%
- ICU admissions: 4.7 to 11.2%
- Deaths: 1.4 to 2.6%
- Age 65 to 74 years
- Hospitalizations: 28.6 to 43.5%
- ICU admissions: 8.1 to 18.8%
- Deaths: 2.7 to 4.9%
- Age 75 to 84 years
- Hospitalizations: 30.5 to 58.7%
- ICU admissions: 10.5 to 31.0%
- Deaths: 4.3 to 10.5%
- Age >85 years
- Hospitalizations: 31.3 to 70.3%
- ICU admissions: 6.3 to 29.0%
- Deaths: 10.4 to 27.3%
- Age <20 years
- References
XXI. Prognosis: Mortality
- Large number of asymptomatic and undiagnosed cases makes mortality estimate difficult
- Mortality overall 0.6 to 0.9% based on extrapolated undiagnosed cases
- Mortality (Worldwide)
- France: 15.3%
- Italy: 14.4%
- U.K.: 14.1%
- Mexico: 11.7%
- Sweden: 10.4%
- Ecuador: 8.4%
- Canada: 8.1%
- U.S.: 5.7%
- Johns Hopkins Coronavirus Resource Center (accessed 6/9/2020)
- Mortality: Cohorts
- See Severe Cases above for comorbidity related mortality risks
- By Age
- Age <=54 years old: <1% Mortality
- Age 70-79 years old: 8% Mortality
- Age >80 years old: 10-27% Mortality
- By Age in ICU
- Age 16 to 49 years old: 25%
- Age 50 to 59 years old: 41%
- Age 60 to 69 years old: 56%
- Age >70 years old: 69%
- (2020) MMWR Morb Mortal Wkly Rep 69(12):343-6 [PubMed]
- By Severity
- Hospitalized patients with Pneumonia have a 4-15% risk of death
- Acute Respiratory Distress Syndrome (ARDS) is associated with 51% mortality
- Intubated patients have mortality rates as high as 81%
XXII. Prevention: General Measures
- Social distancing
- Keep at least 6 foot (1.8 m) distance between others (greater distance may be required indoors)
- Wearing masks (cloth or surgical masks) prevents COVID-19 transmission
- Wearing in indoor public spaces helps protect both the wearer and especially those around them
- Cloth Mask if asymptomatic
- Surgical mask if symptomatic and in healthcare facility
- Infectious persons may be contagious days before symptoms manifest
- Consider masking in any indoor space including home when virus exposure is possible
- Mask should cover both mouth and nose
- Consider outdoor masks when social distancing (6 feet) cannot be maintained
- Evidence for masking as primary prevention is strong
- Wearing in indoor public spaces helps protect both the wearer and especially those around them
-
Vaccination
-
SARS-CoV-2 Vaccine
- Two mRNA Vaccines (Pfizer, Moderna) released and FDA approved in U.S., December 2020
- Expect flu-like symptoms (Fatigue, myalgias), especially after second dose
- Both initial U.S. COVID-19 Vaccines are mRNA Vaccines with a unique mechanism
- https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/
- mRNA is taken up by cells, translated to covid spike protein which is then expelled extracellularly
- Antibody forms to COVID-19 spike protein after 2 Vaccine doses spaced 21-28 days apart
- The mRNA is fragile and degrades soon after injection, and does NOT affect DNA
- Two mRNA Vaccines (Pfizer, Moderna) released and FDA approved in U.S., December 2020
-
Influenza Vaccine (October)
- Does not protect against COVID-19, but also does not lower Immune System or make COVID-19 more likely
- Patients have been infected with both Influenza and COVID-19 with higher morbidity and mortality
- Reduces clinical visits for Influenza
- Reduces potential COVID-19 exposures (while seeking healthcare)
- Reduces risk of lung injury from Influenza (and possible risk for worse outcome in COVID-19)
- Reduces diagnostic confusion in differentiating Influenza presentations from COVID-19 presentations
-
SARS-CoV-2 Vaccine
- Surgery
- Postpone any non-urgent surgery due to 50% risk of pulmonary complications in first 30 days after diagnosis
XXIII. Prevention: Transmission
- Move patient to airborne infection isolation room or unit with negative airflow
-
Personal Protection Equipment (N95 Mask, gown, Eye Protection and gloves) applied with donning and doffing
- https://www.youtube.com/watch?v=bG6zISnenPg
- Doffing is the highest risk time and should follow a careful protocol (consider assigned staff to help direct)
- See Donning and Doffing Personal Protection Equipment
- See Personal Protection Equipment
- See Respiratory Personal Protective Equipment (includes N95 Mask, PAPR)
- Hand Hygiene with soap and water (or >60% Alcohol hand cleanser)
- Disinfect surfaces
XXIV. Prevention: Social Isolation Precautions
- Social distancing is helps to slow COVID-19 infection spread, but it does have mental health risks
- Social distancing is associated with Increased rates of depressed mood, anxiety, Substance Abuse
- See Psychological First Aid
- Reduce Excessive Worry
- Avoid over-checking the news or social media (limit to once or twice daily)
- Choose reliable resources for information
- Perform regular Exercise
- Practice Relaxation Techniques
- Stay connected via phone and video conferencing with friends and family
- Patient Resources
- See Suicide Risk
- Disaster Distress Help Line
- References
- (2020) Presc Lett 27(5): 25-6
XXV. Resources
- Johns Hopkins Coronavirus Resource Center
- BMJ
- Infectious Disease Society of America (IDSA)
- National Institutes of Health (NIH)
- EM:Rap Covid19 Update (March 31)
- EM:Rap Covid19 Update (March 25)
- CDC COVID-19
- COVID-19 (EM-CRIT: Internet Book of Critical Care)
- Corependium (Mason and Herbert)
XXVI. References
- (2021) Presc Lett 28(1): 1-3
- Reuter (2020) Crit Dec Emerg Med, Covid19 Edition, 3-13
- Fei Zhou (2020) Lancet , pre-publication online
- Levitan (2020) ACEP Now
- COVID-19 Ventilation: Quick Reference Guide (Bolton Critical Care Team)