COVID-19 Study Notes

COVID-19

SARS-CoV-2

Disease

  • COVID-19
  • SARS-CoV-2
  • 2019-nCov
  • HCOV-19
  • Virus Name

Coronavirus Structure

  • Medium-sized virus, but with the largest mRNA genome.
  • Enveloped positive-sense stranded RNA.
  • mRNA is encased in a nucleocapsid.
  • Lipid Bilayer disrupted by soap.
  • Corona refers to the crowns formed by spikes.
  • Glycoprotein Spike (S) Peplomer facilitates attachment to human cell receptors in the upper or lower airway.

Upper Respiratory Infections (URIs)

  • Normal human coronaviruses cause 5-10% of common colds/URIs, with outbreaks up to 30%.
  • 229E and NL63 are alpha coronaviruses.
  • OC43 and HKU1 are beta coronaviruses.
  • These attach predominantly to receptors in the upper airway (receptors: aminopeptidase N, dipeptidyl peptidase 4).
  • Seasonality is unpredictable (generally winter, but persists year-round), with different patterns in tropics versus temperate regions.
  • Symptoms include URI symptoms, croupy or dry cough, rarely pneumonia (except sometimes NL63, which usually causes croup), and mild diarrhea in infants.
  • Other URI viruses: Rhinovirus, Influenza A/B, Adenovirus, Parainfluenza, Respiratory syncytial virus, Human metapneumovirus.

Novel Coronaviruses

  • Novel coronaviruses predominantly affect the lower respiratory tract.
  • Examples: SARS, MERS, SARS-CoV-2.
  • Other Lower Respiratory Infections (LRIs):
    • Viral Pneumonia: Influenza (A/B), Adenovirus, Parainfluenza (Type 1-4), Respiratory syncytial virus, Human metapneumovirus, NL63.
    • Typical bacterial Community-Acquired Pneumonia (CAP): Lobar – Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis; Gram-negative, anaerobic if aspiration.
    • Bacterial bronchitis or atypical CAP: Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydia pneumoniae.
  • SARS (2002-2003): Contained, Case Fatality Rate (CFR) 10%. Mortality >50% in those >60 years. High healthcare worker infection and other nosocomial spread. Aerosolization during procedures (intubation, nebs, BiPAP, suctioning).

Novel CoV Attachment

  • ACE-2 Receptors
    • Type 2 alveolar cells - highest concentration
    • Bronchial epithelia
    • Tongue > buccal epithelia
    • Upper Intestinal epithelia
    • Myocardial cells
    • Kidney proximal tubule cells
    • Bladder urothelial cells
  • SARS-CoV-2 binds to ACE-2 Receptor 10-20x more strongly than SARS-CoV.
  • Question of Antibody-Dependent Enhancement (ADE).
    • Antibodies can create a backdoor enhancement for viral replication.
    • Implications on viral replication and vaccine development safety.

SARS-Cov-2 Transmission

  • Novel: No herd immunity, No antibodies cross-reacting.
  • Incubation: 2-14 days (outlier 27 days).
  • Symptom onset median: Day 5-6 from exposure.
  • Doubling time: 6-7 days.
  • High viral shedding occurs early in the disease course, even in those with mild symptoms.
  • Prolonged shedding noted (unlikely reinfection).
  • Up to 23% of transmissions may be due to pre-symptomatic cases.
  • True asymptomatic cases: apparently only 1% per WHO.
  • Viral load apparently still high.
  • Apparently infectious.

SARS-Cov-2 Transmission Routes

  • Respiratory droplets (large - 3 ft, medium - 6 ft).
  • Hand-to-mucus-membrane contact – sticks to skin easily!
  • T-zone: eyes, nose, mouth vulnerable.
  • Viable for 3 days on solids (plastics, porcelain, steel); ~24 hours cardboard, dependent also on temperature/humidity; 3 hours if aerosolized.
  • Airborne – likely not airborne with cough? But certainly possible with intubation, non-invasive positive pressure ventilation, high flow O2, nebulizer, suctioning.
  • Possible fecal/oral route – viral shedding present in stool and diarrhea is common.

Droplet-borne vs. Airborne Transmission

  • Droplet-borne route: Transmitted by medium or large droplets.
  • Short-range airborne route: Transmitted by aerosols.
  • Long-range airborne route: Transmitted by aerosols.
  • Fomite route: Ballistic trajectory of large droplets.
  • Large droplets (>100 μm> 100 \,\mu m): Fast deposition due to gravity.
  • Medium droplets: Between 55 and 100 μm100 \,\mu m
  • Small droplets or droplet nuclei, aerosols (<5 μm< 5 \,\mu m): Responsible for airborne transmission.

Symptoms and Disease Course

  • Week 1:
    • Fever (77-98%) (intermittent or persistent).
    • Fatigue/Malaise (11-52%).
    • Dry cough (46-82%).
    • Dyspnea (3-31%).
    • Less common: Sputum (33%), Myalgia (15%), Headache (13%), Sore throat (14%), Diarrhea (4%), Nausea/Vomiting (5%), Nasal congestion (4%), Hemoptysis (1%).
  • Week 2 (~ day 6-9 of symptoms):
    • ~15-20% develop severe dyspnea due to viral pneumonia.
    • Hospitalization, supportive care, oxygen.
  • Week 2-3:
    • Of hospitalized patients, 1/3 ultimately need ICU care, with up to half needing intubation (i.e., ~5% of total diagnosed cases need ICU).
    • Can rapidly decline (over 12-24 hrs) from mild hypoxia to frank ARDS.
    • Cytokine Storm, Multi-organ failure.
    • Late-stage sudden cardiomyopathy/viral myocarditis, cardiac shock.

Comorbidities and Risk Conditions

  • Age
  • HTN
  • Diabetes
  • Coronary Heart Disease
  • Hep B
  • Cerebrovascular Disease
  • COPD
  • Cancer
  • Children and pregnant women seem to do okay

Diagnosis

  • Travel History, Exposure and Symptoms most important.
  • Person Under Investigation Criteria.
  • No specific physical exam findings. Lungs may have rales or rhonchi.
  • Hypoxia, even silent hypoxia, may be present, especially in elders.
  • Tachycardia and tachypnea.
  • May present as severe asthma or COPD exacerbation.

Ancillary Studies

  • Most Common:
    • WBC usually normal, Lymphopenia in 80%, Mild thrombocytopenia.
    • Low Procal; Bacterial coinfection rare.
    • CRP and D-Dimer elevated proportionate to severity (marker of poor prognosis); DIC over time.
    • Increased ALT/AST to 70-100 range; Occasional increased alk phos.
    • Mild elevation of creatinine.
    • Generally normal troponin.
  • CXR (sensitivity 59%):
    • Bilateral patchy or reticular infiltrates, perihilar infiltrates occasionally.
  • CT scan (sensitivity 86%; much better than RT-PCR!):
    • Bilateral diffuse ground glass opacities, multifocal patchy consolidation, interstitial changes.
    • Changes prior to severe symptom onset!
  • ECHO:
    • Normal EF prior to late-onset sudden cardiogenic shock with dropping EF <10%<10\%.
  • Co-infection rare but possible (5%)

Testing

  • RT-PCR:
    • Real-time Polymerase Chain Reaction of RNA
    • Nasal AND Oropharyngeal Swabs (Collect 2 swabs).
    • Sputum better (but more dangerous to collect?).
    • Stool – not generally used for testing.
    • Blood or urine – virus not detected; blood could be tested for IgM, IgG later. DO get (bacterial) blood cultures for any sick patient.
    • PCR ~ 60-80% sensitive.
    • A single negative RT-PCR doesn't exclude COVID-19 (especially if obtained from a nasopharyngeal source or relatively early in the disease course).
    • If RT-PCR is negative but suspicion remains, consider ongoing isolation and re-sampling several days later.
    • Sensitivity from private labs may vary; no data yet. Also dependent on collection technique and timing – early test on asymptomatic may not be accurate.

How to Collect Swabs

  • Nasopharyngeal AND Oropharyngeal swabs, as separate swabs.
  • If you don’t collect a good sample, it’s a waste of an expensive test and falsely negative!
  • Collect sputum only if patient has a productive cough (do not induce cough).
  • Bronchoalveolar lavage is also high risk to healthcare workers.
  • If intubated, collect tracheal aspirate.

Treatment

  • Mild/moderate symptoms (80%):
    • Outpatient management of symptoms and isolation.
    • OTC Tylenol, cough and cold medications.
    • Avoid steroids (Decadron).
    • Possibly avoid ACEI or Ibuprofen – data unclear!
  • Moderate with risks/severe/critical symptoms (15-20%):
    • Inpatient management and supportive care.
    • Obtain Advanced Directives! Offer Chaplain Support for high-risk patients.
    • Oxygen by NC (place a surgical face mask over NC to reduce aerosolization?).
    • Anticipate rapid progression to High Flow/NRB.
    • Avoid NIV/BiPAP/Bronchoscopy if possible (increased aerosolization -> risk to others!).
    • ARDS: Controlled early intubation with airway pressure release ventilation (APRV), Paralysis, Prone positioning, Flolan. Tight connections of ETT and tubing.
    • Avoid fluid bolusing, sepsis protocol bolusing. NG tube for feeds (ARDS takes time to resolve).
    • Daily labs: Renal, Mag, CBC with diff, DIC labs, ?LFTs, ?ABG (permissive hypercapnia if needed).

Treatment Considerations

  • BiPAP increases the risk of areolation due to positive pressure (as would CPAP), AND generally patients needing BiPAP end up needing intubation.
  • Patients do worse on BiPAP compared to HFNC/NRB.
  • If BiPAP is the ONLY option (no vents) or is needed due to COPD, negative pressure room, air filtration, helmet interface.

Experimental Treatment & Vaccine

  • Experimental:
    • Lopinavir/Ritonavir (Kaletra – protease inhibitors).
    • Ribavirin.
    • Remdesivir.
    • Chloroquine/hydroxychloroquine.
    • High dose IV Vitamin C.
    • IVIG.
    • Serum antibodies of recovered patients.
  • Some Vaccine trials are in Phase 1 Clinical Trials.

Epidemiology

  • Outbreak: "more disease than would be expected"; e.g., measles outbreaks.
  • Endemic: "diseases that remain in an area naturally"; outbreaks can occur in endemic areas; endemic diseases can be exported, causing outbreaks.
  • Public Health Emergency of International Concern (PHEIC): WHO declares if it 1. constitutes a public health risk to other States 2. potentially requires a coordinated international response.
    • Emergency Committee established, unlocks funding, supplies, and international response.
    • Can also increase stigma, xenophobia, economic harm (tourism) to affected country.
  • Epidemic: "regional outbreak of a disease that spreads suddenly and unexpectedly."
  • Pandemic: "worldwide, often rapid, spread of a disease"; WHO declares, with implications for worldwide/national response, World Bank funding, etc.

Mortality Rate

  • Mortality rate (death rate): Number of deaths in general or due to specific cause in a particular population per unit of time. e.g., mortality rate of influenza per week is total deaths related to influenza.
  • Epidemic threshold: level of incidence (of disease or of death) above which an urgent response is needed; varies by disease. e.g., For influenza, if the mortality rate >7.3%>7.3\%, that is, by definition, an epidemic. Once it drops below that, it is no longer epidemic. CFR is 0.1%0.1\%, but the mortality rate per week in the hospital will rise and fall.

Management of Epidemic

  • Prevention!
    • Safe public health practices – vaccines, WASH (water, sanitation, and hygiene) and IPC (Infection Prevention and Control) measures, Universal Precautions.
    • Surveillance systems of WHO, CDC/Ministry of Health, Public/Community Health.
  • Containment:
    • Isolation of sick persons, Contact Tracing, Quarantine of exposed persons.
  • Mitigation: Nonpharmaceutical interventions
    • Personal – Hand hygiene, Cover cough, Stay away from sick persons, Avoid Face.
    • Social – Social distancing, Canceling mass gatherings/non-essential activities.
    • Environmental – Cleaning measures.

CDC recommendations

  • Doffing technique is even more important than donning!
  • Info and Videos available on CDC
  • Surgical Mask if no N95 and for regular exposure.

Masks and NIOSH Standard Respirators

  • Simple and Surgical masks:
    • NOT a Filter, but stops DROPLETS
    • Recommended for PATIENTS who are coughing and/or if YOU are in close proximity to fluids
    • DON’T touch/adjust it! Stop pulling it down to your neck between patients! Stop putting it on countertops! DON’T stick it in your white coat! (STOP WEARING WHITE COATS!)
  • Respirators: N95 means >95%>95\% of particles/pathogens down to 0.30.3 microns are filtered
    • N = not oil resistant
    • R = mildly oil resistant
    • P = oil resistant (for organic chemical poisoning protection)
    • There are also N99 and N100 and P99 and P100 masks
    • Fit is important!
    • Air valve can help with heat/moisture
    • PAPRs and CAPRs: Powered Air Purifying Respirators, Controlled Air Purifying Respirators