Thu. Jun 30th, 2022

Earlier studies indicated that many illnesses such as diabetes, chronic kidney / lung disease, or conditions (like solid organ transplant or cancer) that lead to immunocompromised states result in a higher risk of hospitalization following infection with the severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2), the pathogen behind the ongoing coronavirus disease 2019 (COVID-19) pandemic. A recent report describes the risk of breakthrough COVID-19 and hospitalizations in this subgroup of people following vaccination.

Study: Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities.  Image Credit: sdecoret / Shutterstock
Study: Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities. Image Credit: sdecoret / Shutterstock


The use of booster doses of vaccination against COVID-19 has been avidly discussed given the continuing high rate of infection with this virus, following the emergence of the Omicron variant and its subvariants with extremely high transmissibility. Such boosters were offered in many countries because available evidence showed rapidly decreasing protective immunity after two doses of the vaccines being used at present.

Older adults with high-risk conditions, including those listed above, were prioritized for these boosters, but the degree of risk to younger people with the same indications is still unclear. One study in US veterans with such illnesses, mostly male, showed that nucleic acid vaccines led to a 95% reduction in infections. The current study, available on the medRxiv * preprint server, aimed to understand both the risk of breakthrough infection and severe outcomes in this population.

For this purpose, the investigators developed a platform to evaluate this risk, called the Truveta platform.

What did the study show?

The study included over 2 million people, classified into cohorts based on the presence of four different illnesses and one control cohort. Some individuals were therefore assigned to more than one cohort.

The results show that the highest risk of breakthrough infection is found in those with chronic lung disease, with a 43% increase in risk, and people with diabetes, who have a 30% increase.

However, when it comes to hospitalization, patients with chronic kidney disease had a more than doubled risk even though their risk of infection was lower than those in other groups. The risk was increased by 80% and 50% in those with diabetes and immunocompromised states, respectively.

What are the implications?

The results clearly show that breakthrough infection with the virus occurs to a greater extent among people with some underlying medical conditions than the controls. The greatest increase in risk over baseline is among those with diabetes, chronic lung disease, or chronic kidney disease, even after adjusting for age, sex, race, and ethnic origin. The reason for this higher risk could be the deterioration in the immune response as a result of these conditions.

Studies in unvaccinated individuals with these comorbidities have shown the same pattern. The results also corroborate an earlier report of reduced vaccine effectiveness in a population of US male veterans with a high prevalence of other underlying medical conditions.

A doubling of the odds for hospitalization compared to the vaccinated population confirms earlier findings that people with conditions known to produce impaired immunity fare worse when infected with the virus. This also underlines the need to protect these groups with booster vaccines.

Interestingly, the group with the lowest increase in breakthrough infection was that with immunocompromised states, compared to other comorbidities. This could mean they protected themselves more carefully by behavioral modifications like mask-wearing or social distancing than people in the other groups.

Again, people with chronic lung disease were most likely to be infected by breakthrough infections but least likely to be hospitalized. This group already had greater access to steroids, and supplemental oxygen before COVID-19 or the disease designation included an overly broad range of diseases, so it did not help identify the actual increase in risk due to this condition.

Further research must look at how the presence of multiple such illnesses interact to produce a higher risk of breakthrough infection and adverse outcomes following COVID-19. Such data will help individuals, agencies, and governments to make better recommendations about booster doses of the vaccination for such groups.

The findings of this study improve the evidence and support recommendations for people with comorbidities such as chronic kidney disease, chronic lung disease, diabetes or people who are immunocompromised to receive the primary vaccination sequence as well as a booster dose. ”

* Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice / health-related behavior, or treated as established information.


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