Severe cases of COVID-19 are related to ageing of immune system

Severe cases of COVID-19 are related to the ageing of the immune system and to acute immunodeficiency. It is what the new study led by the Oswaldo Cruz Institute (IOC/Fiocruz) and by the Federal University of Rio de Janeiro (UFRJ) shows, published in the academic journal Journal of Infectious Diseases.

By analyzing blood samples of patients that have been hospitalized with the disease, the researchers detected signs of hyperactivity, exhaustion and ageing of the defense cells known as T helper cells. According to scientists, the data shows loss of responsiveness of these cells in severe COVID-19 cases, which may favour secondary infections and reinfections.

The research was carried out by the Immunobiological Technology Institute (Bio-Manguinhos/Fiocruz), by the Marine Hospital Marcílio Dias, by the Federal Rural University of Rio de Janeiro (UFRRJ), by the Federal Fluminense University (UFF) and by the National Institute of Metrology, Standardization and Industrial Quality (Inmetro), along with IOC/Fiocruz and UFRJ. At IOC/Fiocruz, the Immunoparasitology and Thymus Research Laboratory took part in the work.

Exhaustion and senescence

Coordinator of the study, the researcher of the Immunoparasitology Laboratory of the Oswaldo Cruz Institute (IOC/Fiocruz) and professor at the School of Medicine of the UFRJ, Alexandre Morrot, explains that the T helper cells act as conductors at the immune system. While fighting the infection, those cells recognize viral proteins and activate defense cells responsible for fighting the virus and producing antibodies.

“In patients with severe COVID-19, we observed that the T CD4 cells [T helper cells] are in the final stage of differentiation, presenting signs of exhaustion and senescence. Those cells lost the capacity of clonal expansion, which means they will not multiply when getting in contact with viral proteins and will not be able to lead an efficient immune response”, states the immunologist.

According to the researcher, the condition is characterized by an acute immunodeficiency state. The drop in immunity makes the individual more vulnerable to contracting other infections, such as bacterial pneumonia, which is common among hospitalized COVID-19 patients.

The acute immunodeficiency also explains a phenomenon that has been attracting attention during the pandemic: reinfections. Since the beginning of the state of emergency in public health, the registers of individuals who had been reinfected by Sars-CoV-2, even after severe COVID-19 cases, have surprised scientists. It is because acute viral infections usually produce a strong immunological memory, which avoids, for instance, that the same person contracts measles or chickenpox twice.

“The reinfection occurs in a small fraction of cases, but it is more common than expected. The disfunction of the T CD4 cells [T helper cells] might explain the lack of long-term immunological memory”, says Morrot.

Immune Hyperactivation

The research compared samples pertaining to 22 hospitalized patients with severe cases of COVID-19 with samples taken from healthy individuals. Besides the presence of molecules considered as senescence and exhaustion markers in T helper cells, the researchers also found high levels of inflammatory substances unleashed by those cells in the patients’ blood plasma.

According to scientists, the data shows a process of hyperactivation, which leads the lymphocytes to the final stage of cellular differentiation, resulting in exhaustion and ageing of the immune system. “It reinforces the importance of anti-inflammatory therapies, aimed at controlling the exaggerated immune response, which is a villain in COVID-19 cases”, states Morrot.

The analysis only includes the acute phase of infection. Therefore, the researcher adds that is not possible to point out if there will be any long-term damage to the patients’ immune system. “Scientific literature shows that exhausted cells can regain their functions. Since senescent cells can die out and be replaced by new cells. It is possible that, a couple of months after the disease, patients will not have these changes anymore, but these cases need to be tracked”, states the immunologist.

The research was funded by the Carlos Chagas Filho Foundation for Research in the State of Rio de Janeiro (FAPERJ), the Inova Fiocruz Program, the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (Capes), and the Mercosur Structural Convergence Fund (FOCEM). The research was developed in the scope of the National Institute of Science and Technology in Neuroimmunomodulation (INCT-NIM) and of the Research in Neuroinflammation Network of Rio de Janeiro.