Coronavirus

Coronaviruses are a group of related viruses that contain positive-sense, single-stranded RNA. Coronavirus derives its name from “κορώνα” in Greek, which translates as “crown,” after the small club-shaped proteins visible as a ring around the viral envelope in electron micrographs. Coronaviruses have large genomes, a propensity for mutation, and frequent recombination events that have resulted in a diversity of species. These new species are capable of rapid adaptation to new hosts and ecologic environments. New coronavirus infections have appeared in both humans and animals. Coronaviruses are known to be the cause of some cases of the common cold, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).

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Classification

RNA Viruses Flowchart Classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Structure

  • Spherical
  • 120 nm in diameter 
  • Usually distinguished by its club-shaped or “crown-like” surface proteins
  • Enveloped, with the viral envelope containing the following proteins:
    • Spike (S) protein
    • Hemagglutinin esterase (HE) protein
    • Membrane (M) protein
    • Envelope (E) protein
  • The nucleocapsid is large and has helical symmetry.
  • Has a single-stranded RNA genome of approximately 26–31 kilobases
Envelope proteins are denoted Coronavirus

Envelope proteins are denoted:
S: spike
HE: hemagglutinin esterase
M: membrane
E: envelope
N: nucleocapsid
(+)ssRNA: positive-sense single-stranded RNA

Image: “Structure of coronavirus” by Nongluk S et al. License: CC BY 4.0

Clinically relevant species

  • The family Coronaviridae comprises 2 subfamilies:
    • Letovirinae (has no medically relevant species)
    • Orthocoronavirinae is divided into 4 genera:
      • Alphacoronavirus and Betacoronavirus (infect mammals)
      • Gammacoronavirus and Deltacoronavirus (mainly infect birds)
  • Most of the human-infecting species of coronavirus are found within the Betacoronavirus genus. The most relevant ones include:
    • Human coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-2293)
    • Severe acute respiratory syndrome coronavirus (SARS-CoV)
    • Middle East respiratory syndrome-related coronavirus (MERS-CoV)
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Pathogenesis

Transmission

  • Reservoirs:
    • Chiroptera (bats) are thought to be the origin host for all alphacoronaviruses and betacoronaviruses and, therefore, all human coronaviruses.
    • Camels can also be a reservoir for MERS.
    • Birds are the natural reservoirs and hosts for all of the gammacoronaviruses and deltacoronaviruses.
  • Routes of transmission:
    • Fecal–oral
    • Respiratory droplets and airborne spread
    • Contact with infected surfaces and fomites
    • Vertical transmission has been reported for SARS-CoV-2.

Virulence factors

Most coronaviruses have 4 structural proteins: S, E, M, and N.

  • S, E, and M proteins create the viral envelope. 
  • The N protein forms a complex with RNA (nucleocapsid) and aids in the regulation of viral RNA synthesis.
  • The M protein projects on the external surface of the envelope and is important for viral assembly. 
  • The E protein has an unclear function, although it may aid in virus release.
  • The S protein is a club-shaped surface projection that gives the virus its characteristic crown-like appearance on electron microscopy and is responsible for receptor binding and fusion with the host cell membrane.

Replication cycle

  1. Coronaviruses bind to the host cell surface via the S proteins.
    • Viral entry occurs either by receptor-mediated endocytosis or through membrane fusion. 
    • The virus escapes the acidified environment of the endosomes by transporting itself to lysosomes. 
  2. Coronaviruses have single-stranded, positive-sense RNA that can directly produce the proteins and new genomes in the cytoplasm.
  3. The negative-sense strand template RNA is produced. 
  4. The new viral proteins are translated by the host’s ribosomes.
  5. The nucleocapsid protein binds with genomic RNA, and protein M is integrated into the membrane of the endoplasmic reticulum along with proteins S and HE. 
  6. An assembled nucleocapsid that contains the RNA moves into the endoplasmic reticulum to be encased and is released by exocytosis.
Coronavirus replication

Replication cycle of coronaviruses:
1. Coronaviruses bind to the host cell surface via the S proteins. Viral entry occurs either by receptor-mediated endocytosis or through membrane fusion. The virus escapes the acidified environment of the endosomes by transporting itself to lysosomes.
2. Coronaviruses have single-stranded, positive-sense RNA that can directly produce the proteins and new genomes in the cytoplasm.
3. The negative-sense strand template RNA is produced.
4. The new viral proteins are translated by the host’s ribosomes.
5. The nucleocapsid protein binds with genomic RNA, and protein M is integrated into the membrane of the endoplasmic reticulum (ER) along with proteins S and HE.
6. Assembled nucleocapsid that contains the RNA moves into the ER to be encased and is released by exocytosis.

Image: “The infection life cycle of coronavirus” by C. Michael Gibson et al. License: CC BY-SA 3.0

Diseases Caused by Coronaviruses

  • Common cold:
    • The common cold is usually caused by rhinoviruses.
    • However, coronaviruses cause 15% of common colds.
    • Incubation period: 3 days
  • GI infections:
    • Far less commonly caused by coronaviruses
    • Incubation period: 3 days
    • Usually presents as a very mild infection that causes diarrhea, diffuse abdominal pain, and vomiting
    • Rarely, can lead to neonatal necrotizing enterocolitis
  • MERS:
    • Emerged in 2012 in Saudi Arabia from dromedary camels.
    • Incubation period: 5 days
    • Clinical presentation ranges from asymptomatic infection to acute upper respiratory illness.
    • Can lead to rapidly progressive pneumonitis, respiratory failure, septic shock, and multiorgan failure, resulting in death. 
  • SARS:
    • Emerged in 2003 in southern China from civet cats.
    • Incubation period: 4–6 days 
    • Clinical presentation ranges from mild, flu-like illness with full recovery (25% of cases), to severe respiratory infection (approximately 70%), to death from respiratory failure (approximately 10%).
    • Usually manifests as low-grade fever, muscle pain, lethargy, cough, sore throat, and malaise
    • Can progress to dyspnea, pneumonia, respiratory failure, and death
  • Coronavirus disease 2019 (COVID-19):
    • Emerged in November 2019 in Wuhan, China, from horseshoe bats and caused a global pandemic
    • Incubation period: 2–14 days
    • Clinical presentation can range from asymptomatic or mild infections will full recovery (80% of cases), to severe respiratory infections (15%), to critical disease with multiorgan damage (5%) and death (2.2%). 
    • Usually presents as dry cough, malaise, and fatigue and may be associated with hemoptysis, diarrhea, vomiting, headache, anosmia, dysgeusia, and chest pain
    • Can progress to pneumonia, ARDS, thrombosis, sepsis, multiorgan failure, and death
Table: Epidemiology of respiratory coronavirus diseases
MERS-CoVSARS-CoVSARS-CoV-2
Date of first identified caseJune 2012November 2002December 2019
Location of first identified caseJeddah, Saudi ArabiaShunde, ChinaWuhan, China
Average age56 years44 years56 years
Sex ratio (M:F)3.3:10.8:11.6:1
Table: Frequency of symptoms in respiratory coronavirus diseases
MERS (caused by MERS-CoV)SARS (caused by SARS-CoV)COVID-19 (caused by SARS-CoV-2)
Fever98%99%–100%87.9%
Dry cough47%29%–75%67.7%
Dyspnea72%40%–42%18.6%
Diarrhea26%20%–25%3.7%
Sore throat21%13%–25%13.9%
Ventilator use24.5%14%–20%4.1%

Comparison of Similar Viruses

Table: Comparison of similar viruses
OrganismSARS-CoV-2RhinovirusCoxsackievirus
Characteristics
  • Spherical
  • 120 nm in diameter
  • Large nucleocapsid with helical symmetry
  • +ssRNA
  • Club-shaped S proteins
  • Icosahedral capsid
  • Non-enveloped
  • +ssRNA
  • Genomes 7200 to 8500 nucleotides in length
  • Icosahedral capsid
  • Small and non-enveloped
  • +ssRNA
Transmission
  • Aerosols
  • Respiratory droplets
  • Fomites
  • Vertical
  • Aerosols
  • Respiratory droplets
  • Fomites
  • Fecal–oral
  • Aerosols
  • Respiratory droplets
  • Fomites
Clinical
  • Fever
  • Dry cough
  • Shortness of breath
  • Anosmia
  • Hypoxia
  • Fever
  • Cough
  • Sneezing
  • Myalgia
  • Fatigue
  • Fever
  • Cough
  • Sore throat
  • Conjunctivitis
  • Herpangina
  • Vesicular rash
Diagnosis
  • RT-PCR
  • Serology
Clinical diagnosisClinical diagnosis
Management
  • Careful observation
  • Hospitalization
  • Corticosteroids
  • Monoclonal antibodies
  • Self-limited illness
  • Symptomatic treatment
  • Self-limited illness
  • Symptomatic treatment
Prevention
  • Social distancing
  • Vaccination
  • Personal protective equipment
  • Respiratory hygiene
  • Social distancing
  • Respiratory hygiene
  • Social distancing
  • Respiratory hygiene
+ssRNA: positive-sense single-stranded RNA

References

  1. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. (2003). A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med https://pubmed.ncbi.nlm.nih.gov/12682352/
  2. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. (2003). A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348:1977–1985. https://pubmed.ncbi.nlm.nih.gov/12671062/
  3. Centers for Disease Control and Prevention. (2003). Severe acute respiratory syndrome. Centers for Disease Control and Prevention. Retrieved January 31, 2021, from https://www.cdc.gov/sars/index.html
  4. Armed Forces Institute of Pathology. Severe acute respiratory syndrome (SARS). Armed Forces Institute of Pathology.
  5. Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, et al. (2003) Severe acute respiratory syndrome (SARS) in Singapore: clinical features of the index patient and initial contacts. Emerg Infect Dis 9:713–717. https://pubmed.ncbi.nlm.nih.gov/12781012/
  6. Mole B. (2013). Deadly coronavirus found in bats. Nature. Retrieved 2019 Apr 10 from http://www.nature.com/news/deadly-coronavirus-found-in-bats-1.13597
  7. Hemida MG, Chu DKW, Poon LLM. (2017). MERS coronavirus in dromedary camel herd, Saudi Arabia. Emerging Infectious Diseases 20:1231–1234. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073860/
  8. CDC. (n.d.). MERS in the U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/mers/index.html
  9. Gallegos A. (2020). WHO declares public health emergency for novel coronavirus. Medscape Medical News. Retrieved January 30, 2020, from https://www.medscape.com/viewarticle/924596

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