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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.
    • As of December 2, 2024
      • Variants of interest (VOIs)
        • JN.1
      • Variants under monitoring (VUMs) (as of May 23, 2025)
        • KP.3
        • KP.3.1.1
        • LB.1
        • XEC
        • LP.8.1
        • NB.1.8.1
    • Possible targets for treatment
      • SARS-CoV and several SARS-related coronaviruses (SARSr-CoV) interact directly with angiotensin-converting enzyme 2 (ACE2) to enter target cells
        • The SARS-CoV-2 SB engages human ACE2 (hACE2) with comparable affinity to SARS-CoV SB from viral isolates (i.e., binding with high affinity to hACE2)
        • Tight binding to hACE2 could partially explain the efficient transmission of SARS-CoV-2 in humans
        • SARS-CoV recognizes its entry receptor hACE2 at surface of type II pneumocytes using SB
          • ∼75% overall amino acid sequence identity with SARS-CoV-2 SB and 50% identity within their receptor-binding motifs (RBMs)
          • SARS-CoV S-elicited polyclonal antibody responses potently neutralize SARS-CoV-2 S-mediated entry into cells
        • Previous studies also showed host proteases cathepsin L and TMPRSS2 prime SARS-CoV S for membrane fusion through cleavage at S1/S2 and at the S2′ sites
      • The coronavirus S glycoprotein is surface-exposed and mediates entry into host cells (main target of neutralizing antibodies (Abs) upon infection/focus of therapeutic and vaccine design)
        • S trimers are extensively decorated with N-linked glycans
          • Important for proper folding and for modulating accessibility to host proteases and neutralizing Abs
    • Furin cleavage site at S1/S2 boundary of SARS-CoV-2 S (cleaved during biosynthesis) - a novel feature setting this virus apart from SARS-CoV and SARSr-CoVs
      • Furin-like proteases may expand SARS-CoV-2 cell and tissue tropism compared with SARS-CoV
      • It may also increase its transmissibility and/or alter its pathogenicity
    • Incubation: up to 2 weeks
      • Symptoms may develop 3-10 days
      • Disease course may take 2-3 weeks
    • Transmission: respiratory droplets and body fluids
      • Some evidence shows virus can be viable in the environment for hours
        • Studies seem to indicate virus is stable at cooler temperatures (40°F [4°C])
      • Viral shedding can occur from 8-37 days from time of symptom onset
    • For more genetic information: GISAID Initiative (https://www.gisaid.org/)
  3. 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.
  4. Epidemiology
    • Incidence/Prevalence
      • Emerging disease
      • WHO: Presumed to have originated in Wuhan, China
      • First case in USA 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)
      • 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)

Related Topics

References

  1. 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)
  2. 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
  3. Centers for Disease Control and Prevention (CDC). COVID-19: Healthcare Workers: Information on 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 2025]
  4. 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).
  5. 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.
  6. NIH. Genbank. Available at: https://www.ncbi.nlm.nih.gov/genbank/. [Accessed June 2025]
  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 June 2025]
  8. Chin AWH, Chu JTS, Perera MRA, et al. Stability of SARS-CoV-2 in different environmental conditions. Lancet. Apr 2, 2020.
  9. Zhou F, Yu T, Du R, Fan G, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. Mar 28, 2020;395(10229):1054-1062
  10. Andersen KG. Rambaut A, Lipkin WI, et al. The proximal origin of SARS-CoV-2. Nat Med (2020).
  11. 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
  12. 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.
  13. 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 June 2025]
  14. World Health Organization (WHO). WHO Coronavirus Network (CoViNet). Available at: https://data.who.int/dashboards/covid19/variants. [Accessed June 2025]

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

Updated/Reviewed: June 2025