COVID-19 Risk Stratification - a Missed Opportunity


With any disease, we can assess a person’s risk of having bad outcomes. With COVID-19, data was sparse in the first 6 months because it was new. Since around mid-2020 though, epidemiologists around the world have been getting a better handle on understanding WHICH patients are at the highest risk, WHAT the risks are and HOW the disease spreads. The Fitzpatrick team believes that health authorities at the CDC and State Health Departments have not been communicating the importance of stratified risk for the consequences of COVID-19. These risks are NOT one-size fits all.

  • The main COVID-19 consequence for kids is the risk for “multi-system inflammatory syndrome (MIS-C)” – which is scary, and most physicians have not previously seen many cases of it. Around 1 in every 3,000-4,000 known COVID-19 cases require hospitalization for MIS-C. Risk factors for MIS-C include having obesity, asthma and/or a life-limiting existing condition, being male and/or being between ages 5 and 11.

  • Overall, hospitalization rates for COVID-19 infection in infants and children up to 4 years of age have been up to 14.5 per 100,000. 

  • Death rate: as of October 19, 2022, there have been 556 COVID-19 deaths in 0–4-year-olds and 938 in 5–18-year-olds.  

As one ages, COVID-19 death risk becomes exponentially higher.

Thankfully, the CDC has finally begun teaching about individual risk, but it may be too late in the game to make much of a difference. As researchers and developers of 100’s of disease risk assessment models commissioned by the world’s leading medical associations and biopharma, the Fitzpatrick team feels qualified to discuss disease risk.

Until recently, the CDC and WHO have not sufficiently emphasized the importance of individual risk for developing severe COVID-19. Doctors do not assess/manage 5-year-olds the same as they do 75-year-olds for nearly any diseases. Health professionals across the country depend on the CDC and WHO for guidance. We are pleased with the new CDC Director, Dr. Walensky, and the direction of COVID-19 risk education that was presented in the August 19, 2022 MMWR:

  • “Individual risk for medically significant COVID-19 depends on a person’s risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected.”

  • “The risk for medically significant illness increases with age, disability status and underlying medical conditions, but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments.” The risk for medically significant illness increases with age, disability status and underlying medical conditions, but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments.”
We are extremely pleased to finally see accurate and transparent seroprevalence data from the CDC. The key takeaway from the map below is that about 96% of Americans have already had a COVID-19 infection. We are guessing that this number will not get much higher. In our September, 2020 COVID-19 Immunity Blog, we published that about 6% of the population may have IgG neutralizing antibodies from OTHER coronaviruses that may restrict infection. Maybe we were correct?

  • Using breast cancer risk as an example of HOW people misunderstand risk, a 2011 study showed that only about 35% of women had a realistic understanding of their calculated risk for developing breast cancer. 43% had unrealistic optimism and 12.5% had unrealistic pessimism. A problem with pessimism is that if people with unduly high-risk perceptions also believe there is little they can do to reduce their risk of breast cancer, they may engage in maladaptive coping or unhealthy behaviors like avoiding necessary healthcare.

  • People have a tremendous variation with their understanding of COVID-19 risk. The Fitzpatrick team strongly poses that COVID-19 risk stratification needs to be explained to people just like doctors explain it for other diseases.

  • COVID-19 is primarily spread via airborne transmission. It’s a respiratory disease that is not often spread via surfaces. This is a prime example of health authorities not understanding risk early on andthen instituting ineffective policies. Note that the CDC finally did correct this communication in April, 2021. We discussed airborne transmission in our September 2022 post

The Brookings Institute published a study of 35,000 American adults on COVID-19 health literacy, breaking out the results by political party affiliation. We are mystified by the results:

  • 81% of COVID-19 deaths are ages 65+. Republicans thought this number was 42% and Democrats thought it was 36%.

  • 1-5% of adults need to be hospitalized for COVID-19. 41% of democrats and 28% of republicans thought that 50% or more need to be hospitalized.

  • The study found that 60% of respondents had low ability to understand numeracy (the ability to understand and work with numbers). THIS EXPLAINS A LOT!
    Sadly, we are reminded about low health literacy on a daily basis. This includes TV stories about those at HIGH risk for COVID-19 complications who downplay vaccine efficacy (& then die), as well as those who insist their healthy toddler get vaccinated (and anyone else’s kids).


An exceptional study from Japan shows the odds ratios (OR) for increased risk of developing severe illness in elderly COVID-19 patients with the following conditions: 
  • Collagen disease: OR 2.77
  • Obesity (BMI>/=25): OR 2.05
  • Diabetes: OR 1.41
  • Liver disease: OR 1.89
  • Leukemia and lymphoma: OR 3.63
  • Chronic respiratory disease: OR 1.87
  • Metastatic solid tumor: OR 2.44
  • Renal disease or dialysis: OR 2.28
The number of comorbidities a person has increases risk. For patients under 49 years of age, having 5 or more comorbidities increases their COVID-19 hospitalization or death risk by 12.43x. For patients 50-59, this risk drops to 5x. (comorbidities may include asthma, COPD, dementia, HIV, hypertension or diabetes).

COVID-19 Death Risk by Lab Values: There is actually a data-driven, personalized, mortality prediction model to identify patients at high risk of mortality from COVID-19 via lab values. Here are the findings:

Cardiometabolic Risk Factors: Hypertension (57%) and diabetes (34%) are the most prevalent comorbidities among patients with COVID-19 requiring hospitalization.

Where it Manifests: COVID-19 (SARS-CoV-2) infection occurs through the coupling of the surface of the virus with angiotensin-converting enzyme 2 (ACE2) cells, which acts as a receptor for the virus. ACE2 is mostly present in the lungs and seems to be the main gateway for the virus. It is also present in great amounts in the heart, which can lead to cardiovascular (CV) complications. Interestingly, having asthma neither increases a person’s risk of developing COVID-19, nor for developing severe disease. However, COPD patients indeed, are at greater risk.

Overall Risk for Children: Children and young adults carry only a very small portion of the COVID-19 serious disease burden at the population level. Much of the heated debate about vaccination recommendations and strategies on these age groups is directed at indirect benefits to other age groups and society at large. For example, it is often hoped that vaccinating young populations may help families return to normal activities, and may reduce outbreaks and deaths among older individuals who might otherwise be infected by younger people (in multigenerational households). Young people can be major drivers of active epidemic waves (in terms of their share in numbers of documented cases).


Most COVID-19 hospitalizations and deaths occur in people with major comorbidities. This applies to young ages as well. For children and young adults without comorbidities, the risk of severe COVID-19 disease outcomes is likely far lower than the overall risk in these age groups.


Data from an Israel study compared groups of people who either had a previously documented infection OR received two doses of an mRNA vaccine. The group that had 2 doses of an mRNA vaccine had a much higher risk of breakthrough infection, symptomatic disease and hospitalization than those who had a documented prior infection. This suggests that natural immunity leads to a much stronger and more durable protection. Prior infection immunity was replicated in a recent UK study. Our interpretation is that for low-risk groups (like children and young adults without comorbidities), documented natural infection alone or adding booster(s) to an original vaccine is appropriate. Note that the science of COVID-19 is rapidly changing and some studies have shown higher immunity with vaccines.


  • The 1st (typically, mild) phase occurs in the first 7 days of infection with symptoms characteristic of an upper respiratory tract infection. Nonspecific symptoms such as the loss of taste & smell, and gastrointestinal manifestations may also appear. Approximately 80% of these cases are resolved.

  • The 2nd phase, or moderate pneumonia, occurs in about 15% of the patients around day 10. The symptoms begin to worsen with dyspnea, cough, and oxygen saturation decrease.

  • About 5% of patients evolve to the 3rd phase, or severe pneumonia, with worsening of the respiratory condition, hypoxemia, and fever. This phase is characterized by hyperactivity of the inflammatory immune response, prompting a cytokine storm.

COVID-19 will not be the last “new infectious disease” pandemic that most of us will witness (as we have posted a couple years ago). We hope that the CDC, WHO and industry thought-leaders will teach people about what their risk factors are, earlier on.


Our recent posts:

When did respiratory disease become non-respiratory? (9.21.2022)

COVID-19 Reinfection – It’s Here. Round 2. (1.4.2022)

Kevin Fitzpatrick

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