Clinical features of COVID-19 disease

COVID-19 disease is caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Learn about the clinical features of the virus, and the disease it causes.

The SARS-CoV-2 virus

Coronavirus disease (COVID-19) is caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) The virus was first identified in December 2019.

SARS-CoV-2 is a single-stranded RNA betacoronavirus. It is in the same subgenus as the severe acute respiratory syndrome (SARS) virus. It is more distantly related to the Middle East respiratory syndrome (MERS) virus.1

SARS-CoV-2 contains 4 main structural proteins: spike (S) glycoprotein, small envelope (E) glycoprotein, membrane (M) glycoprotein and nucleocapsid (N) protein.2

Most COVID-19 vaccines target the spike protein, which contains 2 subunits: S1 and S2. S1 contains the receptor binding domain, which binds to the angiotensin converting enzyme 2 receptor on host cells. This allows the virus to enter cells.3

Variant strains

Several SARS-CoV-2 variant strains have been identified. Some variants are associated with higher transmissibility and increased severity or duration of disease. Variants are classified as a Variant of Concern (VOC) or Variant of Interest (VOI).4

As of December 2021, 5 VOCs have been identified:4

  • Alpha (also known as B.1.1.7), first identified in the United Kingdom
  • Beta (B.1.351), first identified in South Africa
  • Gamma (P.1), first identified in Brazil
  • Delta (B.1.617.2), first identified in India
  • Omicron (B1.1.529), first identified in South Africa.

These variants are more transmissible than the wild type of SARS-CoV-2.5 The Omicron variant is more transmissible than other variants. It has replaced Delta as the dominant variant of SARS-CoV-2.6

COVID-19 vaccines based on the ancestral SARS-CoV-2 have lower immunogenicity, efficacy or effectiveness against some variant strains compared with the ancestral strain.

For the Omicron variant, all current ancestral strain-based COVID-19 vaccines have lower immunogenicity after 2 doses. Neutralising antibody titres against Omicron are multiple-fold lower than against other variants, including Delta and the ancestral strain. However, a third dose of an mRNA COVID-19 vaccine resulted in neutralising antibody titres against Omicron that were greater than those after 2 doses against the Delta variant.7 Higher levels of T-cell protection markers were also seen in people who had 3 vaccine doses.7

Vaccine effectiveness against the Omicron variant is lower than for other variants after 2 doses of any of the ancestral strain-based COVID-19 vaccines used in Australia.8 However, a level of protection against symptomatic disease and severe outcomes is retained within the first few months after a second vaccine dose.9 A third vaccine dose has been shown to restore vaccine effectiveness against both Omicron infection and symptomatic COVID-19 disease.8-10

The Moderna bivalent vaccine produces a higher antibody response against the Omicron BA.1 and the BA.4/5 variants compared with the original Moderna vaccine.11 Currently, there are no published studies on the effectiveness of the bivalent vaccine. See COVID-19 vaccine Information for more details.

Clinically significant variations in the efficacy or effectiveness of different vaccines against emerging strains will continue to be monitored.

The disease: COVID-19

SARS-CoV-2 causes:12

  • asymptomatic or mild disease in 81% of cases
  • severe illness (with dyspnoea, hypoxia or >50% lung involvement on imaging within 48 hours) in 14% of cases
  • critical illness in 5% of cases.

Symptoms include:

  • fever and cough (the most common symptoms)13
  • myalgia
  • headache
  • dyspnoea
  • sore throat
  • diarrhoea
  • nausea or vomiting
  • loss of smell or taste (less than 10% of cases)
  • rhinorrhoea (less than 10% of cases).

Risk factors for severe disease

Older age

Older age is by far the strongest risk factor associated with morbidity and mortality from COVID-19.12,14,15 The risk of death from COVID-19 increases throughout each decade of age over 50 years. Compared with people aged <50 years, the risk of death is:16

  • about 2 times as high for people aged 50 to 59 years
  • more than 10 times as high for people aged ≥80 years.

These rates did not change substantially after adjusting for other risk factors.14

In Australia, before the COVID-19 vaccination program started, the COVID-19 case fatality ratio increased substantially with age:17

  • 0.6% in people aged 50 to 64 years
  • 7.0% in people aged 65 to 79 years
  • 33.8% in people aged ≥80 years.

Medical conditions

Certain medical conditions are associated with an increased risk of severe illness from COVID-19, even after the primary course of COVID-19 vaccination. The people most at risk are older adults, people who are severely immunocompromised, and people who have multiple comorbidities, including young children.

People aged 6 months and over in the following groups are likely to have an ongoing increased risk of severe COVID-19 even after primary vaccination. These examples are not exhaustive and providers should use their clinical judgement to assess individual risk.

Conditions

Notes & examples

Immunocompromising conditions

Haematological diseases or cancers

Leukaemia, lymphoma or myeloma resulting in immunocompromise

Recommend discussion with specialist regarding optimal timing of vaccination

Solid organ transplant recipients who are on immune suppressive therapy

Recommend discussion with specialist regarding optimal timing of vaccination

Bone marrow transplant recipients or chimeric antigen receptor T-cell (CAR-T) therapy recipients or those with graft-verses-host disease

Recommend discussion with specialist regarding optimal timing of vaccination

Non-haematological cancer

Diagnosed within the past 5 years or on chemotherapy, radiotherapy, immunotherapy or targeted anti-cancer therapy (active treatment or recently completed) or with advanced disease regardless of treatment 

Survivors of childhood cancers

 

Chronic inflammatory conditions requiring medical treatments

Systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and similar who are being treated.

Primary or acquired immunodeficiency

Including congenital causes of immunodeficiency and HIV/AIDS

Other underlying conditions

Chronic liver disease  Cirrhosis, autoimmune hepatitis, non-alcoholic fatty liver disease, alcoholic liver disease.
Severe chronic kidney disease (stage 4 or 5)

 

Chronic lung disease

Chronic obstructive pulmonary disease, cystic fibrosis, interstitial lung disease and severe asthma (defined as requiring frequent hospital visits or the use of multiple medications).

Diabetes mellitus requiring medication

 
Chronic heart disease Ischaemic heart disease, valvular heart disease, congestive cardiac failure, cardiomyopathies, poorly controlled hypertension, pulmonary hypertension, complex congenital heart disease.
Chronis neurological disease

Stroke, neurodegenerative disease (such as motor neurone disease, Parkinson’s disease), dementia, myasthenia gravis, multiple sclerosis, cerebral palsy, myopathies, paralytic syndromes, epilepsy. 

People with disability with significant or complex health needs or multiple comorbidities that increase the risk of severe COVID-19 Particularly those with trisomy 21 (Down syndrome) or complex multi-system disorders.
Severe obesity with BMI ≥ 40 kg/m2  
Severe underweight with BMI <16.5 kg/m 2  

Aboriginal and Torres Strait Islander people

Aboriginal and Torres Strait Islander people are at increased risk of severe illness and death from COVID-19. This is due to multiple factors, including a high prevalence of underlying chronic health conditions associated with severe COVID-19 and a greater likelihood of living in communities where social distancing cannot be practised.18

Pregnancy

In unvaccinated people, compared with non-pregnant women of reproductive age with COVID-19, pregnant women with COVID-19 have an increased risk of severe illness including:19

  • intensive care admission (OR 2.13, 95% CI: 1.53–2.95)
  • invasive ventilation (OR 2.59, 95% CI: 2.28–2.94)
  • need for extracorporeal membrane oxygenation (OR 2.02, 95% CI: 1.22–3.34).

Factors that increase the risk of severe illness and death from COVID-19 during pregnancy include:

  • increased maternal age
  • high body mass index
  • pre-existing comorbidities.

Infants born to mothers with COVID-19 have a higher risk of:

  • being born preterm (OR 1.47, 95% CI: 1.14–1.91)
  • being admitted to the neonatal intensive care unit (OR 4.89, 95% CI: 1.87–12.81).

Studies conducted earlier in the pandemic have shown that unvaccinated pregnant women are at higher risk of severe outcomes compared with non-pregnant women.20

The risk of severe disease decreases with the number of vaccine doses received. Studies have shown that pregnant women who have received 3 doses of vaccine have low rates of severe COVID-19 with the Omicron strain.21,22

There is a relative lack of data on severe outcomes during the Omicron wave and in vaccinated or boosted pregnant people. In a small study that included 135 pregnant women (70 having received 2 doses, and 13 with 3 or more doses) infected with the Omicron variant, 0% of vaccinated compared with 9.6% of unvaccinated had moderate (lower respiratory tract involvement) or severe infection (reduced blood oxygen levels or lung infiltrates on imaging).21

Mental health conditions

Unvaccinated people with certain mental health conditions are considered to be at greater risk of severe COVID-19 than healthy people without mental health conditions. The ongoing risk of severe COVID-19 in vaccinated people with mental health conditions is unclear.

Working and living conditions

Certain work settings and environmental settings may place people at higher risk of COVID-19 exposure. This is because there is a higher risk of infected people being present and/or because conditions enable the virus to spread rapidly.

These settings include:

  • healthcare facilities (healthcare workers have a 7-fold increased risk of severe COVID-19 compared with non-essential workers, RR 7.42; 95% CI: 5.52–10.00]23
  • aged care and disability care facilities
  • border and quarantine facilities
  • some industries such as meat processing.

More details about COVID-19 are available in the COVID-19 CDNA National Guideline for Public Health Units. Information about Australian epidemiology is available on the Department of Health website, including regular epidemiological reports.

The COVID-19 vaccination program

COVID-19 is a vaccine-preventable disease.

The aim of the COVID-19 vaccination program in Australia is to reduce COVID-19 related harm by preventing serious illness and death, and, as much as possible, disease transmission. Information on COVID-19 vaccination program implementation in Australia is available on the Department of Health website.

The most appropriate use of COVID-19 vaccines is informed by:

  • COVID-19 epidemiology
  • characteristics of COVID-19 vaccines
  • availability of COVID-19 vaccines.

Further reading

1.   Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020;5:536-44.

2.   Dhama K, Khan S, Tiwari R, et al. Coronavirus Disease 2019-COVID-19. Clin Microbiol Rev 2020;33.

3.   Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Immunity 2020;52:583-9.

4.   World Health Organization (WHO). Tracking SARS-CoV-2 variants. Updated 6 July 2021. 2021. (Accessed 20 July 2021). https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

5.   World Health Organization (WHO). Weekly epidemiological update on COVID-19 - 13 April 2021. (Accessed 26 April 2021). https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---13-april-2021

6.   Public Health England. SARS-CoV-2 variants of concern and variants under investigation in England, Technical Briefing 17. 25 June 2021. (Accessed 20 July 2021). https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1001354/Variants_of_Concern_VOC_Technical_Briefing_17.pdf

7.   Jergovic M, Coplen C, Urhrlaub J, et al. Resilient T cell responses to B.1.1.529 (Omicron) SARS-CoV-2 variant. medRxiv 2022;2022:10.1101/2022.01.16.22269361.

8.   Buchan SA, Chung H, Brown K, et al. Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes. medRxiv 2022;2022:10.1101/2021.12.30.21268565.

9.   Sheikh A, Kerr S, Woolhouse M, McMenamin J, Robertson C. Severity of Omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland. Edinburgh Research Explorer 2021;2021:preprint.

10. Garcia-Beltran W, St Denis K, Hoelzemer A, et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 2022;185:457-66.e4.

11. Chalkias S, Harper C, Vrbicky K, et al. A bivalent Omicron-containing booster vaccine against COVID-19. medRxiv 2022:2022.06.24.22276703.

12. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama 2020;323:1239-42.

13. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:759-65.

14. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020;584:430-6.

15. Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. Bmj 2020;369:m1966.

16. Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. Bmj 2020;369:m1985.

17. COVID-19 National Incident Room Surveillance Team. COVID-19 Australia: Epidemiology Report 32: Four-week reporting period ending 3 January 2021. Communicable Diseases Intelligence 2021;45.

18. Yashadhana A, Pollard-Wharton N, Zwi AB, Biles B. Indigenous Australians at increased risk of COVID-19 due to existing health and socioeconomic inequities. The Lancet Regional Health Western Pacific 2020;1.

19. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. Bmj 2020;370:m3320.

20. Zambrano L, Ellington S, Strid P, et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1641-7.

21. Birol Ilter P, S P, Berkkan M, et al. Clinical severity of SARS-CoV-2 infection among vaccinated and unvaccinated pregnancies during the Omicron wave. Ultrasound in Obstetrics and Gynecology 2022;59:560-2.

22. Floyd R, Hunter S, Murphy N, Lindow S, O'Connell M. A retrospective cohort study of pregnancy outcomes during the pandemic period of the SARS-CoV-2 omicron variant: a single center's experience. Int J Gynaecol Obstet 2022;June:doi.org/10.1002/ijgo.14312.

23. Mutambudzi M, Niedwiedz C, Macdonald EB, et al. Occupation and risk of severe COVID-19: prospective cohort study of 120 075 UK Biobank participants. Occup Environ Med 2020.

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