Clinical features of COVID-19 disease

The SARS-CoV-2 virus

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

SARS-CoV-2 is a single-stranded RNA betacoronavirus 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 February 2023 Omicron and its subvariants are the currently circulating VOCs.4 Previous variants (Alpha, Beta, Gamma and Delta) are no longer classified as VOCs.}

^{Omicron is more transmissible than both the wild type of SARS-CoV-2 and previous variants.}

Multiple new Omicron subvariants have emerged since the BA.4/5 wave in Australia during July and August 2022, displaying increased immune-escape properties (for example, BQ.1 and XBB).^4,5 These have co-circulated without any specific subvariant establishing clear dominance. Numerous immunological studies report reduced neutralisation of new Omicron subvariants by both vaccine-induced and naturally derived antibodies.^6,7 COVID-19 vaccines may have a reduced and/or shorter duration of protection against infection by these subvariants compared with older variants. Simultaneously, people’s immunity after their last vaccine dose or previous infection wanes with time. Together these have led to, and are likely to continue to cause, periodic surges in COVID-19 cases in Australia and globally. These surges generally resulted in lower reported case numbers and fewer cases of severe illness than previous waves, because increasing numbers of the population have hybrid immunity (from both vaccination and infection). Early evidence suggests that these newer Omicron subvariants do not cause more severe disease compared with the original Omicron subvariant (BA.1).⁸

COVID-19 vaccines based on the ancestral SARS-CoV-2 have lower immunogenicity, efficacy or effectiveness against Omicron compared with the ancestral strain. See COVID-19 vaccine information for more details.

The disease: COVID-19

Symptoms primarily include:

• fever and cough (the most common symptoms)⁹
• 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).

Severe disease is less common since the Omicron strain and its subvariants have emerged and become dominant after November 2021. High rates of hybrid immunity, which is thought to provide better protection than either infection or vaccination alone, have also greatly reduced the likelihood of severe disease and death. Estimates of severe disease vary widely due to varying levels of vaccination and hybrid immunity by country or region. A nationwide Danish study estimated the infection fatality rate in the Omicron era at 1.6 per 100,000 infections in 17 to 35 year olds, through to 15.1 per 100,000 infections in 61 to 72 year olds.¹⁰

Risk factors for severe disease

Older age

Older age is by far the strongest risk factor associated with morbidity and mortality from COVID-19.^11-13 This continues to be true even in individuals who have received a primary course of vaccination, with or without booster doses.^14,15 The risk of death from COVID-19 increases throughout each decade of age over 50 years. In the Omicron era, a study of people who have received both primary and booster vaccine doses found that the risk of death due to COVID-19 was 31.3 times higher for an 80-year-old compared with a 50-year-old.¹⁵

The risk of severe disease (hospitalisation, oxygen or ventilation requirement, or death) versus non-severe disease rises with age. Compared to a person aged 45 to 49 years, the risk was 4.8 times higher for 65 to 69 year olds and 16.6 times higher for those aged 80 years and over.¹⁴

Medical conditions

The evidence around medical conditions which increase the risk of severe COVID-19 has been reviewed and updated in March 2023. Certain medical conditions are associated with an increased risk of severe illness from COVID-19.^15-17 This applies to both unvaccinated as well as vaccinated individuals. The people most at risk are older adults, people who are severely immunocompromised, and people who have multiple comorbidities, including young children. A higher number of concurrent comorbidities cumulatively increases the risk of severe disease.^17,18

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 or booster vaccination. These examples are not exhaustive and providers should use their clinical judgement to assess individual risk. Survivors of childhood cancers are no longer considered to be at significantly increased risk of COVID-19 infections or severe disease based on updated evidence.¹⁹

 

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.²¹ In some regional or remote communities, access to reliable medical care may be more difficult. In older people and those with medical comorbidities, risks of severe disease continue to be higher even if the person has been vaccinated.

Pregnancy

Unvaccinated pregnant women with COVID-19 have an increased risk of severe illness compared with unvaccinated non-pregnant women of reproductive age with COVID-19, including risk of:²²

• 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).

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.^24,25 A cohort study during the early Omicron period showed the risk of critical care admission was 0.3%, which was 75% lower than during the Delta period.²⁶ The paper did not report proportions by vaccination status.

Although the risk is small, COVID-19 in pregnancy during the Omicron period is still associated with increases in maternal morbidity and severe complications, particularly in women who developed severe symptoms or were unvaccinated. A large multinational observational study of pregnant women showed that overall maternal morbidity was slightly increased (relative risk 1.16; 95% CI 1.03–1.31) in infected vs non-infected pregnant women.²⁷ However, women who developed severe COVID-19 symptoms had almost 12 times higher risk of referral to higher dependency care, ICU admission or death. This rose to almost 21 times higher for unvaccinated women, compared to uninfected pregnant women.²⁷ Vaccinated, boosted women had a 76% reduction in the incidence in severe complications compared with unvaccinated women.

Another prospective UK study of hospitalised pregnant women during the Omicron period found 1 in 5 pregnant women admitted to hospital who were not vaccinated had moderate to severe infection, compared with 1 in 10 with 2 vaccine doses, and 1 in 20 with 3 doses. One in ten pregnant women admitted to hospital with symptoms needed respiratory support.²⁸

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.

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.

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 V. 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:e00028-20.
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. (Accessed 6 February 2023). https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
5. New South Wales Ministry of Health. NSW respiratory surveillance report – week ending 07 January 2023. 2023. https://www.health.nsw.gov.au/Infectious/covid-19/Documents/weekly-covid-overview-20230107.pdf
6. Jiang XL, Zhu KL, Wang XJ, et al. Omicron BQ.1 and BQ.1.1 escape neutralisation by omicron subvariant breakthrough infection. Lancet Infect Dis 2023;23:28-30.
7. Kurhade C, Zou J, Xia H, et al. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster. Nat Med 2022:2022.10.31.514580.
8. Karyakarte R, Das R, Dudhate S, et al. Clinical characteristics and outcomes of laboratory-confirmed SARS-CoV-2 cases infected with Omicron subvariants and XBB recombinant variant. medRxiv 2023:2023-01.
9. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:759-65.
10. Erikstrup C, Laksafoss AD, Gladov J, et al. Seroprevalence and infection fatality rate of the SARS-CoV-2 Omicron variant in Denmark: A nationwide serosurveillance study. Lancet Reg Health Eur 2022;21:100479.
11. 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.
12. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020;584:430-6.
13. 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.
14. Vo AD, La J, Wu JTY, et al. Factors associated with severe COVID-19 among vaccinated adults treated in US Veterans Affairs hospitals. JAMA Network Open 2022;5:e2240037.
15. Nafilyan V, Ward IL, Robertson C, Sheikh A, Consortium NCS-IB. Evaluation of risk factors for postbooster Omicron COVID-19 deaths in England. JAMA Network Open 2022;5:e2233446.
16. Hippisley-Cox J, Coupland CA, Mehta N, et al. Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study. Bmj 2021;374:n2244.
17. Yek C, Warner S, Wiltz JL, et al. Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series - 465 Health Care Facilities, United States, December 2020-October 2021. MMWR Morb Mortal Wkly Rep 2022;71:19-25.
18. Butt AA, Yan P, Shaikh OS, Mayr FB, Omer SB. Rate and Risk Factors for Severe/Critical Disease Among Fully Vaccinated Persons With Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in a High-Risk National Population. Clin Infect Dis 2022;75:e849-e56.
19. Gupta S, Sutradhar R, Alexander S, et al. Risk of COVID-19 infections and of severe  complications among survivors of childhood, adolescent, and young adult cancer: a population-based study in Ontario, Canada. J Clin Oncol 2022;40:1281-90.
20. Lang R, Humes E, Coburn SB, et al. Analysis of Severe Illness After Postvaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US. JAMA Netw Open 2022;5:e2236397.
21. Yashadhana A, Pollard-Wharton N, Zwi AB, Biles B. Indigenous Australians at increased risk of COVID-19 due to existing health and socioeconomic inequities. Lancet Reg Health West Pac 2020;1:100007.
22. 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.
23. 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.
24. 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 Obstet Gynecol 2022;59:560-2.
25. 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;159:605-6.
26. Stock SJ, Moore E, Calvert C, et al. Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by Delta and Omicron variants in Scotland: a population-based cohort study. Lancet Respir Med 2022;10:1129-36.
27. Villar J, Soto Conti CP, Gunier RB, et al. Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study. Lancet 2023;401:447-57.
28. Engjom HM, Ramakrishnan R, Vousden N, et al. Severity of maternal SARS-CoV-2 infection and perinatal outcomes of women admitted to hospital during the omicron variant dominant period using UK Obstetric Surveillance System data: prospective, national cohort study. BMJ Medicine 2022;1:e000190.