Comorbidities affect immune response to severe COVID-19

Immune signatures developed in response to severe COVID-19 appear to vary not only according to the principal disease but also with underlying comorbidities, such as hypertension, diabetes, and heart diseases, a new study has found.

Researchers performed high-throughput, high-dimensional single-cell mapping of 121 peripheral blood samples retrieved from 57 patients who had severe COVID-19. An algorithm-guided analysis was performed to assess interactions between immune signatures, comorbidities, and patient outcomes. A parallel group of 21 healthy controls was also included.

Results showed that immune signatures were affected by both COVID-19 and underlying comorbidities. Metabolic syndrome appeared to be marked by immune alterations in both the innate and adaptive responses. Obesity was associated with granulocyte-macrophage colony-stimulating factor expression in CD4+ T effector memory cells, while hypertension coincided with lower levels of CD4^– CD8^– T cells.

Along with other alterations, severe COVID-19 in obese and hypertensive patients was associated with the exhaustion of innate activity. In contrast, type 2 diabetes mellitus was associated with immune markers pointing to the impaired co-stimulation of myeloid cells.

Meanwhile, heart disease and lung-associated disorders in severe COVID-19 patients correlated with hyperactivated and exhausted T and natural killer cells, as indicated by the higher expression of the activation marker CD38 in these cells.

“These results enrich the database of COVID-19 immunopathology and provide a source for more individualized treatments of COVID-19 patients based on their comorbidities,” the researchers said. “Using therapies targeting the immunological changes specific to severe COVID-19 and even a patient’s comorbidities could be a promising tool to alleviate the severity of this disease.”