A study led by the Infectious Diseases research group at the Vall d'Hebron Research Institute (VHIR) has analyzed the differences in the cellular immune response during SARS-CoV-2 infection depending on the severity of the patients. Researchers have found, for the first time for this virus, that long-term resident memory T cells remain in the lungs of people who passed the infection that would allow them to fight against a possible reinfection. The results have been published in Nature Communications.

In the acute phase of the infection, the researchers identified patterns in the response of T lymphocytes in the blood that are associated with the clinical course of the patients. Specifically, hospitalized patients had higher levels of the cytokines IFNg and IL-4, while those with milder symptoms had higher IL-10 levels. "IL-10 is a cytokine that could play an important role in controlling inflammation. If accompanied by an antiviral response, IL-10 creates an environment that favors the resolution of the infection without promoting an exaggerated inflammation, which is associated with the severity of COVID-19”, reasons Dr. Meritxell Genescà, principal investigator of the research group on Infectious Diseases of the VHIR. The most serious patients, in addition, have fewer T lymphocytes, since many of these cells die because of the overstimulation that causes the great inflammation that is generated. This death occurs mainly in the cells that produce IL-10, which worsens the person's situation.

The study was carried out with samples of 46 patients during the first wave of the pandemic: 14 people with symptoms that did not require hospitalization, 20 mild patients that required hospitalization, and 12 seriously hospitalized patients. The work, led by the Infectious Diseases group at the VHIR with Judith Grau and Nerea Sánchez as first authors, has had the participation of the Infectious Diseases, Thoracic Surgery, Pathological Anatomy and Microbiology Services of the Vall d’Hebron University Hospital,the Occupational Risk Prevention Unit and the Diagnostic Immunology research group at the VHIR.

Memory cells in the lung: a barrier to prevent reinfections

On the other hand, it was observed that lymphocytes activated to fight virus infection have markers that indicate that they will move from the blood to the lung. For this reason, they analyzed the persistence of resident T cells in the lung that would serve as memory cells to fight against possible future reinfections.

This type of lymphocyte was studied in seven convalescent COVID-19 patients, who had had different clinical evolutions, as these people needed a biopsy for other causes. Memory T lymphocytes were found in the lung up to 10 months after infection, which would indicate that it would be a long-term memory. Thus, in the event of a new SARS-CoV-2 infection, the response against the virus would be localized in the lung. "The respiratory tract is the entry route for the virus, therefore, these cells would give a much faster and more efficient response, essential to limit its spread and the disease", adds Dr. Genescà.

Resident memory T cells have previously been described for other viral and bacterial infections in different organs and tissues. In the lung, for example, some of them target cold or flu viruses, but this is the first time they have been identified for SARS-CoV-2.

Based on the results, Dr. María José Buzón, head of the HIV Translational Research line in the research group on Infectious Diseases at the VHIR, explains that “to know if a person has an immune memory or not when faced with an infection, analyzing blood antibodies or cells does not give us all the information, since the presence of memory resident T lymphocytes in the lung is also important”. Although, in clinical practice, they could not be easily identified since it requires a biopsy that is invasive, it is relevant that these cells have been found even in people who passed the infection in a very mild way, not only in the most severe cases.

More knowledge for the generation of future vaccines

The results of the study also highlight that the type of immune response that patients develop is related to the protein or proteins that the immune system recognizes from SARS-CoV-2 when it enters the body. This fact could be related to the development of vaccines for COVID-19. Currently, all available vaccines target the S protein of SARS-CoV-2, a key protein for the virus to enter cells. In this sense, new vaccines could include other parts of the virus, not just protein S. The authors of the work emphasize that studying the types of immune response and to which parts of the virus respond the different memory profiles generated will help the development of more effective vaccines.

To continue studying immunity against SARS-CoV-2, VHIR researchers are currently analyzing the differences between the immune response that occurs in naturally infected patients or in vaccinated people.