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Subsections
COVID-19 (Coronavirus Disease 2019): Background and Pathophysiology

Infectious Diseases

COVID-19 (Coronavirus Disease 2019): Background and Pathophysiology

Background

  1. Definition
    • Highly transmittable respiratory illness with a wide range of associated symptoms
      • Caused by the new coronavirus SARS-CoV-2 (formerly 2019-nCoV)
    • COVID-19 (novel Coronavirus Disease-2019) is the disease, SARS-CoV-2 is the virus
  2. General Information
    • First identified in Wuhan, Hubei Province, China
    • Outbreak of pneumonia of unknown etiology in Wuhan City
      • Initially reported to WHO on December 31, 2019
      • First case in the USA confirmed January 21, 2020 in Washington State
      • Declared a global pandemic by WHO on March 11th, 2020
    • COVID-19 illness severity categories
      • Asymptomatic or Presymptomatic Infection:
        • Individuals who test positive, but have no symptoms
      • Mild Illness:
        • Persons having any of the signs/symptoms of COVID-19 without SOB, Dyspnea or abnormal chest imaging:
        • Signs such as:
          • Fever
          • Cough
          • Sore throat
          • Malaise
          • Headache
          • Muscle pain
      • Moderate Illness:
        • Individuals with evidence of lower respiratory disease by clinical assessment, or
        • Imaging and a SpO2 ≥ 94% on room air
      • Severe Illness:
        • Individuals with RR > 30 bpm
        • SpO2 < 94% on room air
        • PaO2/FiO2 < 300 mmHg
        • Lung infiltrates >50%
      • Critical Illness:
        • Individuals with respiratory failure
        • Septic shock
        • Multiple organ dysfunction
    • Severe COVID-19 patients develop a systemic inflammatory response that can lead to:
      • Lung injury
      • Multisystem organ dysfunction
    • In pediatric patients, radiographic abnormalities are common and, for the most part, should not be used as the sole criteria to define COVID-19 illness category. Normal values for respiratory rate also vary with age in children, thus hypoxia should be the primary criterion to define severe illness, especially in younger children.
    • Availability of vaccine
      • The best COVID-19 vaccine is the first one that is available to you. Do not wait for a specific brand.
        • All currently authorized and recommended COVID-19 vaccines are:
          • Safe
          • Effective
          • Reduce risk of severe illness
        • CDC does not recommend one vaccine over another.
      • If they have been exposed to COVID-19 and do not meet all those criteria, they should follow standard CDC guidance, which says that
        • People who have not had COVID-19 within the past 3 months should quarantine for 14 days following an exposure
        • This can be shortened to 10 days without testing if the person does not display any symptoms during daily monitoring, or to 7 days with a negative test and no sign of symptoms, according to the CDC
    • As of November 29, 2024
      • Variants of interest (VOIs)
        • BA.2.86
        • KP.3
      • Variants under monitoring (VUMs)
        • XEC
  3. Epidemiology
    • Incidence/Prevalence
      • Emerging disease
      • WHO: Presumed to have originated in Wuhan, China
      • First case in USA was announced January 21, 2020
      • > 770,000,000 confirmed cases worldwide
      • July 31, 2023-August 27, 2023
        • 1.4 new million COVID-19 cases (WHO)
    • Mortality/Morbidity
      • > 6,900,000 deaths worldwide
      • July 31, 2023-August 27, 2023
        • > 1800 deaths (WHO)
      • 2023 USA
        • 916,300 people hospitalized
        • 75,5000 deaths
      • Higher risk of mortality amongst older adults, especially with underlying illnesses/immunocompromised (e.g., DM, cardiovascular disease, etc.)
      • Pneumonia is a significant risk for mortality
        • See the MuLBSTA Score
        • Specific for Viral pneumonia similar to COVID-19 induced, but may not yet be valid for COVID-19 patients (use with caution)

Pathophysiology

  1. Pathology of Disease
    • Virology
      • Coronaviridae family--> Orthocoronavirinae subfamily--> 4 genera (alpha, beta, gamma, delta coronavirus)
        • Variants being monitored
          • Alpha (B.1.1.7 and Q lineages)
          • Beta (B.1.351 and descendent lineages)
          • Gamma (P.1 and descendent lineages)
          • Epsilon (B.1.427 and B.1.429)
          • Eta (B.1.525)
          • Iota (B.1.526)
          • Kappa (B.1.617.1)
          • 1.617.3
          • Mu (B.1.621, B.1.621.1)
          • Zeta (P.2)
        • Variants of Concern
          • Delta (B.1.617.2 and AY lineages)
          • Omicron (B.1.1.529)
      • Enveloped, positive-sense, single-stranded RNA
      • For more genetic information, see Global Initiative on Sharing All Influenza Data (GISAID) Initiative
    • Mechanism
      • Entry of SARS-CoV-2 into host cell depends on its club-shaped transmembrane spike (S) glycoprotein (View image)
        • S-glycoprotein comprises 2 functional subunits: (View image)
          • S1 subunit: Binds to host cell receptor
            • Specifically, the receptor binding domains (RBDs) of S1 binds to host receptors
            • RBDs are highly variable and may cause high mutagenicity of the virus
          • S2 subunit: Fuses with host cell membrane
      • First, S1 subunit binds to the host cell receptor Angiotensin-converting enzyme 2 (ACE-2)
        • SARS-CoV-2 shares 75% S-protein identity with SARS-CoV; both use ACE-2 as the entry receptor
      • Next, the S-protein gets primed/cleaved by the serine protease TMPRSS2
      • Priming allows S2 to fuse the viral and host cellular membranes
      • Lastly, viral RNA gets released into host cell where it replicates
    • Transmission
      • By respiratory droplets predominantly, but aerosolization possible from speaking or singing (especially indoors/prolonged exposure) > fomite. Virus found in respiratory secretions and saliva.
      • Viral shedding by asymptomatic people may represent 40–50% of total infections, though some uncertainty remains regarding how much they contribute to totals
        • Viral shedding may antedate symptoms by up to 3+ days.
        • Viral titers are highest in the earliest phases of infection, 1-2 days before the onset of symptoms, and then in the first 4-6 days of illness in patients without immunosuppression
      • Why widespread and rapid transmission occurs is not completely understood
        • Asymptomatically infected people who shed and spread is a likely explanation.
          • People who are not ill will not as carefully take measures to avoid spread.
            • Some are super-spreaders, which may be due to inherent characteristics (e.g., their speech generates aerosol, loud speaking, etc.)
          • Mass gatherings especially indoors in smaller spaces or with poor ventilation appear to enhance transmission
          • This is in large part the rationale behind universal mask use.
        • Aerosol spread appears possible in some settings.
          • The amount of airborne transmission frequency is debated, evidence of viral RNA beyond expected droplet range especially indoors if poor ventilation exists.
            • 6-ft distancing remains a routine social distancing recommendation; however, uncovered face/sneezes may generate partial aerosolization with some activities for greater distances.
          • To date, there has not been a well-documented outbreak traced to aerosol transmission at a distance (e.g., through HVAC ventilatory systems or airplane ventilation)
        • Whether droplet or aerosol, concern for spreading by those ill or not ill but infected is the rationale for the universal wearing of masks while in public or if one cannot maintain social distancing, at least six feet
        • Stool shedding also described later in the disease, but uncertain what role, if any, that plays. Some researchers using as a tool to predict community outbreaks.
  2. Etiology/Risk Factors
    • Etiology
      • Novel beta-coronavirus: SARS-CoV 2
        • Zoonotic pathogen
          • Shares 88% sequence identity with 2 bat-derived SARS-like CoV, suggesting it originated in bats (most likely reservoir)
            • Shares 79% sequence identity with SARS-CoV and 50% with MERS-CoV
          • There are recurrent spillovers of coronaviruses in humans; suggests future zoonotic transmission events may occur
    • Risk factors
      • Travel to endemic areas within the last few weeks/months
      • Close contact with COVID-19 patient
      • Older age, especially > 65 yrs and people with comorbidities appear more likely to develop an infection with severe symptoms and be at risk for death
        • Age gradient, with > 85 years highest; 80% of U.S. deaths are age > 65 years
        • CDC reports 94% of COVID-19-related deaths to have at least one comorbidity present
      • Comorbidity risks:
        • CKD
        • COPD
        • Immunocompromised state from solid organ transplant
        • Obesity
        • Serious heart conditions (Heart failure, CAD, cardiomyopathies)
        • Sickle cell disease
        • DM2
      • People with the following conditions might be at an increased risk for severe illness from COVID-19:
        • Asthma (moderate to severe)
        • Cerebrovascular disease
        • Cystic fibrosis
        • HTN
        • Immunocompromised state from:
          • Blood or bone marrow transplant,
          • Immune deficiencies
          • HIV
          • Corticosteroid use
          • Use of other immune weakening meds
        • Neurologic conditions (e.g., dementia)
        • Liver disease
        • Pregnancy
        • Pulmonary fibrosis
        • Smoking
        • Thalassemia
        • DM1
      • In the U.S.:
        • Obesity appears to be emerging as a risk factor, BMI ≥ 30, in nearly half of hospitalized patients
        • Blacks, Native Americans and Latinx are hospitalized at rates greater than expected on a population basis, as well as higher mortality rates.
      • Younger adults are also being hospitalized in the U.S., reflecting increasing percentages in many states and in these later phases of the pandemic account for most cases.
      • Children appear less symptomatic with infection and less prone to severe illness.
        • Children < 1 yr at high risk for severe illness
        • Children 1–10 yrs: low risk of disease and transmission
        • Children 10–18 yrs: higher risk of disease compared to 1–10 yr group; however, a higher risk of transmission in some studies than adults
        • CDC suggests children with medically complex diseases including neurologic, genetic, metabolic conditions, or who have congenital heart disease are at higher risk for severe illness from COVID-19.

Related Topics

References

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  2. Centers for Disease Control and Prevention (CDC). COVID-19. Available at: https://www.cdc.gov/covid/hcp/?CDC_AAref_Val=https://www.cdc.gov/coronavirus/2019-ncov/hcp/index.html. [Accessed June 2024]
  3. Centers for Disease Control and Prevention (CDC). Overview of COVID-19 Vaccines. Available at: https://archive.cdc.gov/#/details?url=https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/overview-COVID-19-vaccines.html. [Accessed November 2024]
  4. Centers for Disease Control and Prevention (CDC). Stay Up to Date with Vaccines. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html. [Accessed June 2024]
  5. Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020;395(10223):514-523
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  7. GISAID. China, Japan and Thailand share genetic sequence and metadata of newly discovered coronavirus BetaCoV. Available at: In Focus: https://www.gisaid.org/. [Accessed November 2024]
  8. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. Mar 11, 2020.
  9. Gorbalenya, A.E., Baker, S.C., Baric, R.S. et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 5, 536–544 (2020).
  10. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2)
  11. Morris DH, van Doremalen N, Holbrook MG, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. The New England Journal of Medicine. 2020; 382:1564-1567.
  12. NIH. Genbank. Available at: https://www.ncbi.nlm.nih.gov/genbank/. [Accessed November 2024]
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  14. Paul G Auwaerter,et al John Hopkins ABX Guide/COVID-19. Available at: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540747/all/Coronavirus_COVID_19__SARS_CoV_2_ [Accessed November 2024]
  15. Walls AC, Park YJ, Tortorici MA, et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020 Mar 6. pii: S0092-8674(20)30262-2
  16. World Health Organization (WHO). Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. March 2020. Available at: https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations. [Accessed June 2024]
  17. World Health Organization (WHO). TAG-VE statement on Omicron sublineages BQ.1 and XBB. Available at: https://www.who.int/news/item/27-10-2022-tag-ve-statement-on-omicron-sublineages-bq.1-and-xbb. [Accessed November 2024]
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Contributor(s)

  1. Tom, Jubil, MD
  2. Cherian, Geo, MD
  3. Cox, Takema, DO, MBS
  4. Ho, Nghia, MD
  5. Wedro, Benjamin, MD
  6. Singh, Ajaydeep, MD
  7. Ausi, Michael, MD, MPH

Updated/Reviewed: November 2024