Without illness and vaccinations
Immunity to SARS-CoV-2 in people who have not had COVID-19 – reality
We wrote about a study conducted by German scientists when its materials had not yet been reviewed and were available on the preprints website. Now the article has been published in the journal Nature (Braun et al., SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19).
Memory T cells capable of recognizing fragments of SARS-CoV-2 were found in the blood of healthy people who did not have COVID-19. They were found in 24 of 68 healthy subjects (35%). Moreover, it was noticed that the immunity of patients with COVID-19 and the immunity of healthy people reacts to different fragments of the viral envelope. T-helpers of patients with COVID-19 recognized the spike protein SARS-CoV-2 along its entire length, and in healthy people, immunity is activated by areas of spike protein similar to those characteristic of spike proteins of generally harmless coronaviruses of the "common cold".
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Immune cells responding to SARS-CoV-2 have been found in people who have not had COVID-19
Denis Yatsutko
COVID-19 coronavirus disease is clinically manifested in very different ways: from asymptomatic infection to severe pneumonia, acute respiratory failure and death. There is still no clear understanding of what causes this or that scenario of the course of the disease, what are the physiological mechanisms of such variability. The role of the immune response is also poorly understood: to what extent and in what way the immune response affects pathogenesis.
Simply put, the action of the immune system is reduced to the work of cells (cellular immunity) and molecules, in particular, antibodies, located in blood plasma and other body fluids (humoral immunity). The reactions of coronavirus-induced antibodies are variable and relatively short-lived, while cellular immunity (this is when the body gets the ability to produce T-cells specifically reacting to the pathogen) is more stable, but in the case of a new coronavirus infection it is still poorly studied. A large group of scientists from Berlin, having decided to fill this gap in the scientific picture of infection, began studying the body's T-cell reactions to the SARS-CoV-2 coronavirus and, among other things, discovered the unexpected – T-cells reacting to SARS-CoV-2 in healthy people who had never been sick with COVID-19.
T-cells (T-lymphocytes) – the most important element of acquired immunity. They mature in a special gland, the thymus, where they undergo a kind of training, acquiring T-cell receptors and surface markers (coreceptors, for example, CD4), allowing them to recognize antigens dangerous to the body (for example, viruses), in order to then destroy them. At the same time, both in order to identify a person, it is enough to see his face or, for example, compare a fingerprint with those stored in the database, and to identify a virus, it is enough for a T-cell to identify one of the viral proteins (or even part of it). Because of this, since identical or similar proteins can occur in the structure of different viruses, cross–reactive cellular immunity is possible when T–helpers trained to recognize one antigen react more or less successfully to another.
In the new work, German scientists focused on studies of the 2002-2003 coronavirus epidemic (atypical pneumonia, SARS), which showed that the most important protective role was played by the adaptive immune response of the body specifically to the spike-shaped glycoprotein (the same S-protein that makes up the "crown" of the coronavirus). They suggested that the induction of CD4+-T cells reacting to the spike-like glycoprtein SARS-CoV-2 will also be crucial in the immune response to a new coronavirus infection. Therefore, they investigated the presence and phenotypic characteristics of such cells in patients with COVID-19, as well as in healthy people with a negative test for antibodies to SARS-CoV-2 (seronegative).
Blood was taken from the subjects, then, using a centrifuge, lymphocytes were isolated from it and stimulated with peptides corresponding to different parts of the thorn-shaped protein of the SARS-CoV coronavirus-2. Thus, in the blood samples of the subjects, scientists found T-cells specifically reacting to the S-protein SARS-CoV-2. 12 out of 18 COVID-19 patients had CD4+-T cells reacting to peptides from the N-terminus of the S-protein (S-I-reactive), and 15 – to peptides from the C-terminus (S-II-reactive).
But it is much more curious that such T-cells were found in 23 out of 68 healthy subjects with a negative serological test. At the same time, S-II-reactive cells were found in all these 23 people, but only six of them had S-I-reactive cells.
People often suffer from respiratory infections caused by various human coronaviruses (HCoV). They are usually perceived as "seasonal colds". The authors of the study write that human coronaviruses are responsible for 20% of all "colds" and an adult becomes infected with HCoV on average once every two to three years.
The HCoV spike protein is similar to the SARS-CoV-2 spike protein, however, there is more similarity between them in the C-end region than in the N-end region. Given these data, the researchers assumed that the S-II-reactive cells in the tested people who were not sick with COVID-19 remained from the immune response to HCoV infections previously tested. After testing 18 of 68 COVID-19-negative subjects for antibodies against four HCoV varieties (HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43), the authors found IcG antibodies against four HCoV in all 18 tested. According to the authors, protective antibodies may weaken over time, but cellular immunity may persist. And there is a possibility that in the case of HCoV and SARS-CoV-2, cellular immunity is partly cross-reactive and may affect the easier course of COVID-19 in patients with coronavirus "seasonal colds".
The authors believe that their work should initiate worldwide studies to assess the contribution of previously developed cross-reactive immunity to the course and clinical outcomes of COVID-19, and may also help in the development of vaccines.
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