Understanding the Range of Disease Severity in COVID-19

Two years into the global COVID-19 pandemic, the momentum behind disease prevention to reduce the risk of transmission and to protect against serious  illness and hospitalisation is growing. Despite much progress, each new surge presents new challenges and difficult milestones, as the world has surpassed 400 million infections, and more than six million people have died.1 As COVID-19 cases continue to rise worldwide, prevention remains the ultimate goal to reduce the spread of infection and protect against severe illness and death.2,3

What role have new variants played?

Despite increasing vaccination rates and ongoing public health measures, the SARS-CoV-2 virus has continued to evolve and mutate, spinning off several variants from Alpha through Omicron.4 Several of these, including Omicron (now referred to as BA.1) and its sublineage BA.2, have been named “variants of concern” (VOC) by the World Health Organization.5-6 Recent variants and subvariants are more transmissible, increasing the chances of becoming infected and spreading the virus, even when taking appropriate precautions.4

Illness due to the recent Omicron surge has often been labelled as “mild.”7 Still, the surge has led to increased hospitalisations and deaths in hundreds of thousands of people worldwide1,8 – largely in those who are unvaccinated,9 but also in immunocompromised people who cannot mount a strong enough immune response to vaccines alone.10 Protecting vulnerable populations such as the immunocompromised from getting COVID-19 could also help prevent viral evolution, which is an important factor in the emergence of variants. This can happen because some immunocompromised patients remain at risk of getting the virus despite vaccination. These individuals also can experience more severe disease and remain contagious for longer, if infected.10-11

What do the different stages of illness from COVID-19 look like?

If a person becomes infected with COVID-19, the degree of illness depends on many factors. In fully vaccinated people with healthy immune systems, symptoms tend to be less severe than in unvaccinated or immunocompromised people, and the infections are less likely to progress to more severe disease.9-10 For vulnerable populations, including immunocompromised, elderly, or those with underlying conditions, who are at high risk of progressing to severe illness or becoming critically ill, disease prevention remains an important goal in the fight against the pandemic.3

In general, symptoms of mild illness from COVID-19 infection include headache, fever, cough, fatigue, and shortness of breath,12 although some variants may cause different symptoms.7 Signs of more serious illness can include difficulty breathing, pain or pressure in the chest, confusion, and bluish lips or face, and may require evaluation by a health professional.12

Global health authorities advise patients who have symptoms to get tested to confirm an infection and to follow local guidance on isolation measures after a positive test.3,12 This will help reduce the risk of infection to others and people who are at risk of becoming seriously ill. In many cases, the infection will resolve without medical intervention.13 However, some ill patients may need to be examined by a doctor or health clinic to see if treatment is needed to prevent symptoms from progressing to even more severe disease.3,13

Spectrum of COVID-19 Illness

Who is most likely to develop severe symptoms from COVID-19?

People who are unvaccinated, people who are immunocompromised, and individuals with certain health conditions have a higher risk of becoming very sick (and potentially dying) from COVID-19.9-10

  • Vaccination can provide stronger, more consistent immunity against severe disease versus natural immunity in unvaccinated people.14 Data published in August 2021 showed that those who are unvaccinated are 29 times more likely to be hospitalised with COVID-19 and have a significantly higher risk of death than those who are fully vaccinated against the disease.15
  • People with weakened immune systems may not have the same response to vaccination as non-immunocompromised people and have a higher risk of severe and long-lasting COVID-19 infections.16
  • Underlying health conditions such as cancer, type 2 diabetes, obesity, high blood pressure, and heart disease may weaken the body’s immune response. Having any of these conditions can make a person more likely to get severe symptoms if infected.17

A trial published in December 2021, found that people who were severely ill with COVID-19 were at a significantly increased risk for future mortality than those who remained uninfected or experienced milder symptoms from an infection.18

A global ambition to reduce COVID-19 risks

The global community has come a long way in the fight against COVID-19, thanks to scientific progress and efforts to promote better public health. But in the face of an evolving virus and the continuing emergence of new, highly transmissible variants, COVID-19 infection rates and fatalities remain high around the world.19 Scientists are learning more about why new versions of the coronavirus emerge, spread faster, and what this could mean for future prevention and treatment efforts.19 Their research is part of an ongoing global effort to achieve the ultimate goal of prevention and to protect the most vulnerable patient populations against severe illness and death.2-3


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2. Centers for Disease Control and Prevention. COVID-19 Overview and Infection Prevention and Control Priorities in non-U.S. Healthcare Settings. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/non-us-settings/overview/index.html#prevention-treatment. Last accessed: March 2022.

3. World Health Organization. (‎2021)‎. COVID-19 clinical management: living guidance, 25 January 2021. World Health Organization. https://apps.who.int/iris/handle/10665/338882. License: CC BY-NC-SA 3.0 IGO. Available from: https://apps.who.int/iris/bitstream/handle/10665/338882/WHO-2019-nCoV-clinical-2021.1-eng.pdf?sequence=1&isAllowed=y. Last accessed: March 2022.

4. Centers for Disease Control and Prevention. What You Need to Know About Variants. Available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/about-variants.html. Last accessed: March 2022.

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6. World Health Organization. Statement on Omicron sublineage BA.2. Available from: https://www.who.int/news/item/22-02-2022-statement-on-omicron-sublineage-ba.2. Last accessed: March 2022.

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13.   National Institutes of Health. Clinical Management Summary. Updated February 1, 2022. Available from: https://files.covid19treatmentguidelines.nih.gov/guidelines/section/section_121.pdf. Last accessed: March 2022.

14. Centers for Disease Control and Prevention. (2021 October 29). New CDC Study: Vaccination Offers Higher Protection than Previous COVID-19 Infection [Media statement]. Available from: https://www.cdc.gov/media/releases/2021/s1029-Vaccination-Offers-Higher-Protection.html. Last accessed: March 2022.

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Veeva ID: Z4-43444
Date of preparation: April 2022