What is the contemporary risk of poor outcomes from Coronavirus Disease 2019 (COVID-19) infection for patients under 65 years of age with compromised health status or comorbidities?

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Last updated: May 20, 2025View editorial policy

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From the Guidelines

The risk of poor outcomes from COVID-19 infection for patients under 65 is significantly lower than for older adults, with most experiencing mild to moderate symptoms that resolve without hospitalization. For healthy individuals under 65, the risk of hospitalization is approximately 1-5%, with death rates below 0.5% 1. However, certain factors increase risk even in younger populations, including obesity, diabetes, hypertension, heart disease, lung disease, immunocompromised status, and cancer. The presence of multiple comorbidities can increase risk substantially, with each additional condition potentially doubling the risk of severe outcomes.

Key Factors Influencing Risk

  • Obesity
  • Diabetes
  • Hypertension
  • Heart disease
  • Lung disease
  • Immunocompromised status
  • Cancer Vaccination remains highly effective at preventing severe disease, with up to 90% reduction in hospitalization risk among vaccinated individuals 1. Current COVID-19 variants generally cause less severe disease than earlier strains, though they may be more transmissible. For those who do contract COVID-19, early treatment with antivirals like Paxlovid (nirmatrelvir/ritonavir) within 5 days of symptom onset can further reduce hospitalization risk by 85-90% in high-risk individuals. The risk assessment for COVID-19 continues to evolve as population immunity increases through vaccination and prior infection, generally trending toward lower severity for most people under 65.

Reducing Hospitalization Risk

  • Vaccination: up to 90% reduction in hospitalization risk
  • Early treatment with antivirals: 85-90% reduction in hospitalization risk for high-risk individuals According to a study published in the Journal of the American College of Cardiology 1, pre-existing medical conditions, particularly when 2 or more co-occur, also significantly increase the risk for severe COVID-19 outcomes. Another study published in Clinical Nutrition 1 reported that age and comorbidities are strong predictors of hospitalization, critical illness, and mortality in COVID-19 patients.

Comorbidities and Risk

  • Presence of multiple comorbidities can increase risk substantially
  • Each additional condition potentially doubles the risk of severe outcomes It is essential to consider these factors when assessing the risk of poor outcomes from COVID-19 infection for patients under 65. By prioritizing vaccination and early treatment, individuals can significantly reduce their risk of hospitalization and severe disease.

From the FDA Drug Label

The baseline demographic and disease characteristics were balanced between the PAXLOVID and placebo groups. The proportions of subjects who discontinued treatment due to an adverse event were 2. 0% in the PAXLOVID group and 4. 2% in the placebo group. At baseline, mean age was 45 years; 51% were male; 71% were White, 15% were Asian, 9% were American Indian or Alaska Native, 4% were Black or African American, and 1% was missing or unknown; 41% were Hispanic or Latino; Eligible subjects were 18 years of age and older with at least 1 of the following risk factors for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or were 60 years of age and older regardless of comorbidities.

The contemporary risk of poor outcomes from COVID-19 infection for patients under 65 is not directly stated in the provided drug label. However, the label does provide information on the demographics of the study population, including a mean age of 45 years.

  • The study included subjects with at least one risk factor for progression to severe disease, but it does not provide a clear answer to the question of risk for patients under 65 without any risk factors.
  • The label also mentions that PAXLOVID is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19. Therefore, no conclusion can be drawn about the contemporary risk of poor outcomes from COVID-19 infection for patients under 65 based on the provided information 2.

From the Research

Contemporary Risk of Poor Outcomes from COVID-19 Infection for Patients Under 65

The contemporary risk of poor outcomes from COVID-19 infection for patients under 65 can be understood by examining the relationship between age and COVID-19 severity.

  • Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65 3.
  • Comorbidities such as cardiovascular disease, diabetes, and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor 3.
  • A study found that the crude effect of age on severe COVID-19 outcomes substantially decreased when adjusting for important age-dependent risk factors, such as diabetes, hypertension, and compromised immunity 4.
  • Adjusting for all six comorbidities indicates a 2.7% risk increase for disease severity, and no additional risk of death per year of age 4.

Factors Influencing COVID-19 Outcomes in Patients Under 65

Several factors can influence COVID-19 outcomes in patients under 65, including:

  • Comorbidities, such as cardiovascular disease, diabetes, and obesity 3, 4.
  • Immune system function, with immunocompromised patients being at higher risk of poor outcomes 5.
  • Access to effective treatments, such as antiviral medications like nirmatrelvir/ritonavir 6, 5.

Management of COVID-19 in Patients Under 65

The management of COVID-19 in patients under 65 involves:

  • Early diagnosis and treatment with antiviral medications, such as nirmatrelvir/ritonavir 6, 5.
  • Management of comorbidities and underlying health conditions 3, 4.
  • Monitoring for signs of severe disease, such as acute respiratory distress syndrome and multiple organ failure 3.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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