Coronaviruses have been present within the human population for generations ¹ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now the third of Betacoronavirus genus transferred to humans in the last twenty years. It has reported the highest contagiousness but the lowest mortality rate ².It emerged in China in December 2019. From that point on, it would mark the beginning of a pandemic that would affect millions of people worldwide due to its high transmissibility ³.

COVID-19, resulting disease from SARS-CoV-2, presents common clinical manifestations for most patients, which are fever, cough, and a grave «flu» that can evolve into acute respiratory distress syndrome (ARDS), pneumonia, renal failure, and death ⁴. It has also been demonstrated that it can present post-COVID-19 complications, such as myocardial inflammation, arrhythmia, pneumothorax, and pleural effusion ⁵. A meta-analysis carried out in January 2021 has shown that SARS-CoV-2 is highly contagious when symptoms appear, but this contagiousness decreases to almost zero after ten days in mild-moderately ill patients. The same study suggests that it has a mean incubation period of 6.38 days, a time that can be considered relatively short if we take into account that the adaptive response takes between 15 and 21 days ⁶. Once the virus enters the body and the innate immune response fails, the second line of defense, the adaptive immune system, is put into action thanks to the dendritic cells, which carry the virus antigen to the CD4⁺ T cells (helper T cells) ⁷. These cells are responsible for triggering the humoral and cellular responses. This first response is in charge of defending the extracellular space through the action of antibodies produced by B cells ⁸. The second one is focused on killing the virus in the intracellular space through the activity of CD8⁺ T cells (cytotoxic T cells). These cells are of particular interest in this review because after people get infected with SARS-CoV-2, they tend to generate CD8⁺ T cells that can target more than 15 distinct fragments of coronavirus proteins inside the infected cells giving them more protection to new variants. In contrast to B cells antibodies, which target the spike protein on the virus’s surface, a protein that is capable of mutations ⁹.

Knowing about the adaptive response to certain diseases is essential for creating vaccines; in this case, it is necessary to understand how this response works against SARS-CoV-2. The first step for such an understanding is quantifying the virus-specific CD4⁺ and CD8⁺ T cells ¹⁰. CD4⁺ and CD8⁺ T cells primarily react to the spike protein on the coronavirus to initiate antiviral immunity[UdMO1] ¹¹. In addition, depending on the patient and the severity of SARS-Cov-2, the immune response of T cells can range from optimal to suboptimal[UdMO2] ^12. Over the years, the population of naïve T cells has declined. Still, conversely, antigen-experienced memory T cells become an essential part of the T cell population due to their memory system ^13,14. The older the person, the better the immune response to previously exposed pathogens.

T cells are easier to induce a response against new pathogens in children. For this reason, it has been observed that children who become infected are not significantly affected by the disease ¹³. Furthermore, CD4⁺T cells stimulate B cells to produce viral-specific antibodies and cytotoxic CD8⁺T cells to target virus-infected cells ¹¹. In addition, activated CD4⁺ and CD8⁺ T cells have been found to help both clearances of the acute infection caused by the disease and protective immunity against reinfection by establishing immunological memory against the pathogen ¹⁵.

CD4⁺ T cells are central organizers of antiviral immune responses. Furthermore, some of the functions of CD4⁺ T cells in SARS-CoV-2 infection are their ability to differentiate into various helper and effector cell types. This serves different actions: helps CD8⁺ T cells, instructs B cells, recruits innate cells, has direct antiviral activities, and facilitates tissue repair ¹⁶ (Figure 1). In situations of uncontrolled immune or inflammatory responses, CD4⁺ T cells can cause pathology ¹⁷. Different studies have made it possible to find CD4⁺ T cells that are reactive against SARS-CoV-2 in patients who have not suffered from the disease, which is suggested according to Bacher. P., et al (2020) arise in response to infection by the common cold coronavirus (CCCoV) ¹². In addition, a correlation between the reappearance of CD4⁺ T cells and the patient’s recovery has been observed when the patient has a severe SARS-CoV-2 infection ¹⁸. This suggests that the patient’s cells have already acquired some immunity against SARS-CoV-2 and give them protection against the disease, which causes them to recover.

For some time now, vaccines have become a preventive, routine, and effective measure to reduce the eradication rate or eradication of certain viral diseases⁵³. Furthermore, vaccines help in the creation of acquired immunity. Viral vector vaccines use a modified version of a virus, which is different from the target virus for which they carry important instructions to our cells. Also, vaccines prevent disease among vaccinated people. In addition, vaccines reduce infections even among people who are not vaccinated through herd immunity. Herd immunity happens if a sufficient proportion of the population is immunized or is immune to the virus⁵⁴. Pharmaceutical companies can use the knowledge obtained in the realization of vaccines against SARS-CoV it is necessary to explain the importance of SARS-CoV before mention as “tool” to develop vaccines against SARS-CoV-2: “SARS-CoV have significant similarities in their genomic sequences because they come from the same family and share a common cell receptor (ACE2) ^55,56. By sharing a receptor, it helps in the develop and obtain vaccines against SARS-CoV-2. Since it has been observed that SARS-CoV-2 and SARS-CoV-2 spike mRNA vaccines have been shown to mediate protection against severe disease, which can occur as early as ten days after the first vaccination when neutralizing antibodies are barely detectable ^57,58. Therefore, vaccine-induced CD8⁺ T cells may be the primary protection mediators at this early stage ⁵⁸.

Almost all the COVID-19 vaccines approved worldwide were designed to require two doses to reach stronger protection against the disease ⁶⁶. The first clinical trials revealed that a weak immune response was found after only one dose of the vaccine. Although it offers little protection against the virus, it can potentially lead to partial immunity, which drastically increases the risk that vaccine-resistant variants of SARS-CoV-2 emerge ⁶⁷. On the other hand, the immune responses are more robust after completing the two-dose vaccine series and have shown sustained protection against new variants ⁶⁶. One of the last documented examples is the delta variant, which has been reported a 33% protection after a single shot of a two-dose COVID-19 vaccine, while individuals who completed the two-dose vaccine series reported a 90% protection against this variant ⁶⁶.

Lately, researchers have opted for a new strategy known as heterologous prime and boost. It gives a third dose (booster shot) of a different COVID-19 vaccine after 6 months of the second dose (UPDATE). Studies have shown that persons over fifty years of age who took the booster shot had a 90% lower mortality rate from COVID-19 than those who did not ⁶⁹. The reason behind this is that the neutralizing antibody responses were enhanced to such a level that they exceeded the estimated levels necessary to protect us from the virus ⁷⁰. What remains uncertain is if this third dose will be enough to lengthen the protection gap or if this booster will become a standard measure to control population immunity ⁷⁰.

The SARS-CoV-2 virus population is constantly evolving and will likely remain a part of our lives for many years to come. This virus has revolutionized the world economically and socially. This virus has revolutionized the world economically and socially. In addition, the development of vaccines against COVID-19 is related to immunological memory. To prevent COVID-19 disease and avoid transmission, the vaccine must elicit high titers of neutralizing antibodies. Memory T cells can fight infection if they have a high amount of neutralizing antibodies. Almost all vaccines against COVID-19 attack the spike protein. Older people have a poor T-cell response, so they risk severe COVID-19. Therefore, the elderly should be vaccinated so that the immunization provided by the vaccine occurs long before the infection, which allows the response, expansion, and maturation of the adaptive immune system.

Although the characteristics and functions of the virus have been deciphered during the last two years, there is still to investigate the relationships of SARS-CoV-2 with the severity of the disease, immunological memory, protection, and vaccines. However, studies of antigen-specific CD4⁺T cells, CD8⁺T cells, B cells, and antibodies together in larger cohorts of acute patients, representing a range of disease severity, are needed to understand protective adaptive immune responses mechanisms COVID-19 further. In addition, the scientific community must continue to improve surveillance and monitoring strategies to prevent these occurrences from having such damaging effects in the future.