A study involving IRBLleida explains why patients over the age of 70 were more vulnerable to COVID-19 during the first wave

During the first year of the COVID-19 pandemic, mortality rates were particularly high among patients over the age of 70, at a time when vaccines were not yet available and the reasons for this high vulnerability were unclear. Now, a multidisciplinary study led by researchers from the Biomedical Research Network Centre for Respiratory Diseases (CIBERES) and the Salamanca Biomedical Research Institute (IBSAL), funded by the TV3 La Marató Foundation and the CIBERES-UCI-COVID project, provides an explanation for this phenomenon.

The study, published in the scientific journal GeroScience and which also involved collaboration from, amongst others, the Infectious Diseases unit of CIBER (CIBERINFEC), analysed the response to SARS -CoV-2 in 450 patients admitted to the Arnau de Vilanova and Santa María de Lleida university hospitals and the Río Hortega hospital in Valladolid, and validated its results in an independent cohort of 244 critically ill patients.

Reduced antiviral capacity in older people

The results show that patients over the age of 70 developed a less effective immune response to the virus. Specifically, they produced fewer SARS-CoV-2-specific antibodies and had reduced levels of key molecules involved in antiviral defence, such as granzyme A and interferon gamma. This reduced response capacity resulted in poorer control of the virus, with higher levels of viral load in the blood.

Furthermore, the study found that older patients activated different immune mechanisms to those of younger patients. In older patients, there was a predominance of increased activation of innate immunity, alongside endothelial damage and activation of the coagulation system.

This pattern suggests that, in their attempt to control the infection, elderly patients developed a thrombo-inflammatory response, associated with more severe clinical forms of the disease. Consequently, mortality was significantly higher in this group: approximately 32% in those over 70 years of age compared to 6% in younger patients.

According to study researcher Alejandro Álvaro-Meca, a researcher at CIBERINFEC at Rey Juan Carlos I University in Madrid, 'this biological profile was identified using a machine learning model that enabled the detection of key biomarkers associated with the response in elderly patients'. The model was subsequently validated in an independent cohort of critically ill patients, confirming its robustness.

Tamara Postigo-Casado, the study's lead author and a researcher at IBSAL, highlights that "this work helps us understand how elderly patients respond to a new virus, against which they had no prior immunity, and provides key insights for better protecting this population against future emerging infections".

For their part, the project's principal investigators, Jesús F. Bermejo-Martín and David de Gonzalo, researchers at CIBERES at IBSAL and IRBLleida respectively, emphasise that the availability of vaccines radically changed this scenario: "once vaccinated, older patients were better able to control the virus and avoid the development of this thrombo-inflammatory response, which significantly reduced mortality".

Article: Postigo-Casado T, Ortega A, Álvaro-Meca A, Vélez-Serrano D, García-Mateo N, Tedim AP, et al. Key factors of the deranged antiviral response in elderly patients with COVID-19: a machine-learning analysis GeroScience. Apr 22.

Text: Unidad de Cultura Científica CIBER