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15.3.1.2.1: Coronaviruses

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    MERS-CoV
    "MERS-CoV" by NIAID is licensed under CC BY 2.0

    Recommended guide to SARS-CoV2 by Scientific American: https://www.scientificamerican.com/i...e-coronavirus/ 

    Virus

    • Genetic material: (+)-strand ssRNA
    • Virion structure: helical capsid; enveloped with prominent glycoprotein spikes
      • the name "corona" means crown and refers to the resemblance of the virus to a crown due to the prominent glycoprotein spkies
    • Glycoprotein adhesin(s) (spikes):  simply referred to as spike (S) proteins

    Replication (Figure \(\PageIndex{1}\))

    • Attach to viral receptors in the respiratory tract
      • SARS and SARS-CoV2 (cause of COVID-19) specifically bind to angiotensin-converting enzyme 2 (ACE2) (Figure \(\PageIndex{2}\))
      • ACE2 plays a role in regulating blood pressure/vasoconstriction and is found throughout the body, not just in the respiratory tract
    • (+)-sense RNA is used directly by infected host cell as mRNA to make viral proteins
    • RNA-dependent RNA polymerase (RdRP) is used to make (-)-sense RNA copies of the genome; the (-)-sense RNA can then be used as template to make more (+)-sense RNA genome
      • like in other RNA viruses, the use of an RdRP for genome replication results in a high rate of mutation
    • mRNA is translated into a long polyprotein which is then cut into active proteins by a protease (similar to HIV) (not shown in figure)
    File:Coronavirus replication.png
    Figure \(\PageIndex{1}\): "File:Coronavirus replication.png" by Crenim at English Wikipedia is licensed under CC BY-SA 3.0

     

    clipboard_e09157d745788e99cd56451d64cee931b.png

    Figure \(\PageIndex{2}\): The areas of the body in which ACE2 is expressed are linked to many of the observed symptoms of COVID-19.  In addition to the respiratory tract, ACE2 is expressed in the vascular system (endothelial cells, migratory angiogenic cells, and vascular smooth muscle cells), heart (cardiofibroblasts, cardiomyocytes, endothelial cells, pericytes, and epicardial adipose cells) and kidneys (glomerular endothelial cells, podocytes and proximal tubule epithelial cells). ACE2 is also expressed and functions in the local RAS of the liver (cholangiocytes and hepatocytes), retina (pigmented epithelial cells, rod and cone photoreceptor cells and Müller glial cells), enterocytes of the intestines, circumventricular organs of the central nervous system, upper airway (goblet and ciliated epithelial cells), and alveolar (Type II) epithelial cells of the lungs and pulmonary vasculature. (© 2020 American Heart Association, Inc; Circulation Research. 2020;126:1456–1474. DOI: 10.1161/CIRCRESAHA.120.317015)

    Transmission

    • Inhaled in respiratory droplets
      • SARS-CoV2 (cause of COVID-19) can also
        • be transmitted through aerosols
        • enter through the eye
    • Viruses which cause severe respiratory syndromes (Middle East Respiratory Syndrome (MERS), Sudden Acute Respiratory Syndrome (SARS), and COVID-19) are throught to be of zoonotic origin
      • All three have been found in bats
      • MERS is also found in camels

    Epidemiology

    • Most diseases caused by coronaviruses in humans are mild common colds similar to rhinovirus
      • second most frequent cause of common cold (10 - 15% of colds)
    • For SARS (Sudden Acute Respiratory Syndrome) and COVID-19 the most at risk are
      • healthcare workers
      • others in close contact with infected individuals
      • elderly
      • people with underlying conditions such as high blood pressure (related to the receptor ACE2), diabetes, asthma, COPD (chronic obstructive pulmonary disease)
    • For MERS, close contact with camels is a large risk factor
    • The severe respiratoty syndromes have relatively high mortality rates:
      • SARS 10%
      • MERS >50%
      • COVID-19 
        • Original strain 1.5 - 3.0% in most countries, but as high as 8.6% (depends on medical facilities and treatments available)
        • Current morality rate seems to be decreasing for recent variants (such as omicron) and due to vaccination and developments in treatment

    Clinical Disease

    • Common cold: typical common cold symptoms
    • Common symptoms of the severe respiratory syndromes:
      • high fever
      • shortness of breath
      • difficulty breathing
      • malaise
      • body aches
      • sometimes gastrointestinal symptoms such as diarrhea (about 10-20% of patients)
    • Additional COVID-19 symptoms/effects (note: being COVID-19 is a relatively newly described disease, this information reflects what is currently known to the best of my ability)
      • dry cough
      • loss of taste and smell
      • low blood oxygen
      • lung damage/scarring
      • cardiovascular effects, including blood clots, heart attack, stroke
    • The most severe/fatal cases of COVID-19 result from severe inflammation caused by the immune system in a phenomenon called a "cytokine storm".
      • Immune system overreacts to the extent that there is extensive, system-wide tissue damage
      • "Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation." (https://www.nejm.org/doi/full/10.1056/NEJMra2026131)
    • Some people who have been infected with COVID-19 become "long haulers"
      • Can even occur in people with mild cases
      • symptoms linger for months or development of sequelae
        • myocarditis
        • abnormal heart rhythm
        • persistent shortness of breath
        • fatigue
        • neurological symptoms: dizziness and "brain fog" to seizures and encephalitis

    Treatment and Prevention

    • COVID-19 prevention:
      • vaccination 
      • mask wearing in public
      • limit activities in public places
      • maintain distance from people not in your household (>6 feet)
      • quarantine/isolation: follow current CDC guidelines
    • COVID-19 treatment:
      • Drugs:
        • Monoclonal antibodies can reduce disease severity
        • Remdesivir is a nucleoside analog that can decrease the length of hospitalization
        • Paxlovir (nirmatrelvir and ritonavir) is an oral medication which prevents SARS-CoV2 replication by inhibiting the protease which cuts the synthesized polyprotein into active viral proteins.  This drug greatly reduces the risk of hospitalization if taken early in the infection.
        • Dexamethasone is a steroid that diminishes the immune response.  Helpful to reduce dangerous inflammation in severe disease (prevents/reduces cytokine storm). 
      • Supportive therapy such as supplemental oxygen or ventilators (in the most severe cases)
    • COVID-19 vaccines:
      • There are two types of COVID-19 vaccine that have been or are likely to be approved for use in the US:
        • mRNA (Pfizer-BioNTech and Moderna): mRNA code for the spike protein contained within a lipid vesicle
          • lipid vesicle fuses with cell membrane and releases mRNA into your cells
          • your cells use the mRNA to produce the SARS-CoV2 spike protein and trigger an immune reaction to SARS-CoV2
          • ~94% effective with two doses a few weeks apart
        • viral vector (AstraZeneca)
          • harmless virus capable of infecting humans (an adenovirus in the case of AstraZeneca) is engineered to carry the SARS-CoV2 spike protein gene
          • infected cells produce the spike protein and trigger an immune response to SARS-CoV2
      • Everyone who can should get vaccinated

    15.3.1.2.1: Coronaviruses is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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