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Coronavirus

Micro > Virology > RNA viruses
Classical Coronavirus (see below for SARS, MERS, COVID-19)
  1. Structure
    1. Originally classified as a calicivirus, the coronavirus family has been carved out to it's own classification
    2. Enveloped ssRNA+ virus
    3. produces full lenght negative strand RNA for replication, with individual negative strand mRNAs for coronavirus protein production
    4. buds into rough endoplasmic reticululum, forming envelope, then exocytosed
  2. Pathobiology
    1. Enters cell by attaching ACE-2 surface receptors
    2. optimum temperature for growth is 33-35˚C, therefore infection is most prominant and often localized to upper respiratory epithelium
      1. Animal coronaviruses (SARS, MERS, COVID-19) can replicate at higher temperatures and cause more systemic manifestation
    3. cause 10-15% of URIs in humans
    4. Several serotypes
  3. Epidemiology
    1. Transmitted by respiratory droplets, aerosols, and fomites
    2. Some concern for transmission via fecal oral route in SARS outbreak
    3. incubation period ~3 days for typical Coronavirus infections causing URI symptoms
  4. Disease manifestations
    1. typical "cold" symptoms with rhinorrhea, cough, nasal congestion.
    2. Damage to respiratory epithelium may lead to secondary infections
    3. may exacerbate preexisting medical conditions - asthma, COPD
    4. rare cause of pneumonia - usually in patients with preexisting respiratory conditions and/or immune suppression.
  5. Diagnosis
    1. Typically a clinical diagnosis
    2. PCR can identify strain-specific virus but is generally not helpful in the clinical setting
  6. Prevention
    1. No vaccine exists for common Coronavirus strains
    2. Hand washing
  7. Differential Diagnosis: Rhinovirus, Adenovirus, Influenza A B or C, Coxsackie Virus

Special note on SARS-CoV (Severe Acute Respiratory Syndrome)
  1. Coronavirus zoonosis oringinating from Yunnan China in January 2002
  2. Epidemiology
    1. original reservoir is the Horseshoe Bat, with an intermediary of the Masked Palm Civet. These animals were housed together in "wet markets" allowing cross-infection and eventual transmission to humans
    2. transmission through large respiratory droplets and possibly fomites
    3. little to no asymptomatic transmission
    4. Sicker patients led to more likelihood of transmission
    5. Some affected patients excreted large amounts of virus - 'superseeders'
    6. Nosocomial transmission in healthcare setting was a major driver of the epidemic
    7. >8000 cases worldwide with 784 deaths
    8. International travel was responsible for rapid spread of disease to other sites including outbreaks in Vietnam, Canada, and others
  3. Pathobiology
    1. infects cells via ACE-2
    2. replicates at 37˚C
  4. Disease manifestations
    1. primarily pneumonia
    2. systemic illness with kidney, liver, GI involvement also seen
    3. mortality:
      1. 15% overall
      2. 50% if age >65
      3. higher mortality seen in patients with underlying pulmonary disease (>50%)
  5. Laboratory diagnosis
    1. PCR of respiratory secretions or stool
  6. Prevention
    1. Vaccine not available
    2. Personal protective equipment for contacts of active cases (e.g. hospital worker)

Special note on MERS-CoV (Middle East Respiratory Syndrome)
  1. Coronavirus zoonosis originating from the Arabian Penninsula
  2. Epidemiology
    1. animal reservoirs: bat and camel
    2. majority of cases identified from Saudi Arabia
    3. International travel has led to cases across the world, with a major outbreak in South Korea in 2015 (186 cases, 36 deaths)
  3. Disease Manifestations
    1. primarily pneumonia
    2. systemic illness with kidney, liver, GI involvement also seen
    3. mortality 37%
  4. Laboratory diagnosis
    1. PCR of respiratory secretions
  5. Prevention
    1. Vaccine not available
    2. Personal protective equipment for contacts of active cases (e.g. hospital worker)

Special note on SARS-CoV-2 (COVID-19)

  1. Coronavirus zoonosis oringinating from Wuhan China in December 2019
  2. Epidemiology
    1. original reservoir is the bat, with the intermediate host of the pangolin. These animals were housed together in "wet markets" allowing cross-infection and eventual transmission to humans
    2. International travel was responsible for rapid spread of disease to other sites across the globe
    3. transmission through large respiratory droplets and possibly fomites
    4. Aymptomatic or pre-symptomatic transmission has been proposed as a major driver of infections
  3. Pathobiology
    1. Similar Pathobiology to SARS-CoV
    2. infects cells via ACE-2
    3. replicates at 37˚C
  4. Disease manifestations
    1. primarily pneumonia
    2. systemic illness also seen
    3. kidney
    4. liver
    5. cardiac - carditis
    6. clotting cascade (DVT, embolic phenomena)
    7. multiple other systems described
  5. mortality:
    1. ~2% overall (range 0.7-3.8%)
    2. median age of mortality - 80 years
    3. higher mortality seen in patients with
      1. underlying pulmonary disease
      2. immune suppression
      3. increased BMI
      4. diabetes
      5. high blood pressure
      6. undelying cardiac disease
    4. Significant impact of Age on Mortality in USA
        • Age <40 - 0.2%
        • Age 40-50 - 0.4%
        • Age 50-60 - 1.8%
        • Age 60-70 - 3.6%
        • Age 70-80 - 8.0%
        • Age >80 - 14.8%
  6. Laboratory diagnosis
      1. PCR of respiratory secretions
      2. Antibody testing available but unreliable
  7. Therapy
    1. Aggressive suportive therapy
    2. Anticoagulation for severe illness
    3. Remdesivir (blocks RNA-dependent RNA polymerase)
    4. Convalescent Plasma (passive antibody from healthy survivors of COVID-19)
    5. Steroids for severe lung disease
    6. (Data on therapeutic immune suppression, especially IL-6 inhibition, is controversial)
    7. (Data on hydroxychlorquine is generally not supportive of use)
    8. (Data on use of HIV protease inhibitors is generally not supportive of use)
  8. Prevention
    1. Social distancing, mask wearing, hand washing, societal measures to limit direct spread, aerosols, and fomite transmission
    2. In hospital:
      1. PPE for known or suspected cases
    3. Vaccines are in development





     
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