COVID-19 T Cells Plays Critical Role In Controlling SARS-CoV-2 Coronavirus Besides Preventing Or Reducing Severity Of COVID-19 Disease
Source: COVID-19 T Cells Sep 17, 2020 3 years, 7 months, 1 week, 2 days, 1 hour, 41 minutes ago
COVID-19 T Cells: Since the debut of the SARS-CoV-2, scientist have been trying to figure out if the immune system actually helps or is making things more worse in the case of the COVID-19 disease but a new study by researchers from La Jolla Institute for Immunology- California clearly argues in favor of the immune system.
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By examining all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects, the study team found that SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Also coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19.
It was observed that the coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals > 65 years old. Scarcity of naive T cells was also associated with ageing and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between ageing and impaired adaptive immune responses to SARS-CoV-2.
Furthermore the study reveals that there has been a misplaced focus on antibodies rather that SARS-CoV-2 specific T Cells in terms of treatment protocols and approaches, therapeutics and vaccinations although antibody response is critical in vaccine programs.
Their study findings are published in the peer-reviewed journal: Cell
https://www.cell.com/cell/fulltext/S0092-8674(20)31235-6
The study findings confirms that a multi-layered, virus-specific immune response is important for controlling the virus during the acute phase of the infection and reducing COVID-19 disease severity, with the bulk of the evidence pointing to a much bigger role for T cells than antibodies.
However a weak or uncoordinated immune response, on the other hand, predicts a poor disease outcome. The study findings suggest that vaccine candidates should aim to elicit a broad immune response that include antibodies, helper and killer T cells to ensure protective immunity.
It should be noted however that most of the current vaccine candidates in the phase 3 trials fails to achieve that adequately as the emphasis as always been on mainly eliciting antibodies response.
Senior author Dr Shane Crotty, Ph.D., who co-led the study with Dr Alessandro Sette, Dr. Biol.Sci., both professors in La Jolla Institute for Immunology’s Center for Infectious Disease and Vaccine Research told Thailand Medical news, "
Our observations could also explain why older COVID-19 patients are much more vulnerable to the disease. With increasing age, the reservoir of T cells that can be activated against a specific virus declines and the body's immune response becomes less coordinated, which looks to be one factor making older people drastically more susceptible to severe or fatal COVID-19."
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Dr Sette further added, "What we did not see was any evidence that T cells contribute to a cytokine storm, which is more likely mediated by the innate immune system."
It is known that when the coronavirus SARS-CoV-2 or any other virus for that matter, infiltrates the body, the innate immune system is first on the scene and launches a broad and unspecific attack against the intruder. It releases waves of signaling molecules that incite inflammation and alert the immune system's precision forces to the presence of a pathogen.
Typically within days, the so-called adaptive immune system tools up and moves with pinpoint precision against the virus, intercepting viral particles and killing infected cells.
The body’s adaptive immune system consists of three branches: antibodies; helper T cells (Th), which assist B cell to make protective antibodies; and killer T cells (CTL), which seek out virus-infected cells and eliminate them.
In the latest research, the study team collected blood samples from 50 COVID-19 patients and analyzed all three branches of the adaptive immune system ie SARS-CoV-2 specific antibodies, helper and killer T cells in great detail.
Co-first author and infectious disease specialist Sydney Ramirez, M.D., Ph.D., who spearheaded the sample collection commented, "It was particularly important to us to capture the whole range of disease manifestation from mild to critically ill so we could identify differentiating immunological factors.”
The study team found that similar to their previous study, all fully recovered individuals had measurable antibody, helper and killer T cell responses, while the adaptive immune response in acute COVID-19 patients varied more widely with some lacking neutralizing antibodies, others helper or killer T cells or any combination thereof.
Co-first author and postdoctoral researcher Dr Carolyn Moderbacher, Ph.D added, "When we looked at a combination of all of our data across all 111 measured parameters we found that in general, individuals who mounted a broader and well-coordinated adaptive response tended to do better. A strong SARS-CoV-2 specific T cell response, in particular, was predictive of milder disease. However individuals whose immune response was less coordinated tended to have poorer outcomes."
Significantly, the effect was magnified when the researchers broke down the dataset by age.
Dr Crotty added, "Individuals over the age of 65 were much more likely to have poor T cell responses, and a poorly coordinated immune response, and thus have much more severe or fatal COVID-19."
He further added, "Thus, part of the massive susceptibility of the elderly to COVID-19 appears to be a weak adaptive immune response, which may be because of fewer naïve T cells in the elderly."
Typically naïve T cells are inexperienced T cells that have not met their viral match yet and are waiting to be called up. As we age, the immune system's supply of deployable naïve T cells dwindles and fewer cells are available to be activated to respond to a new virus.
Dr Moderbacher added, "This could either lead to a delayed adaptive immune response that is unable to control a virus until it is too late to limit disease severity or the magnitude of the response is insufficient."
Similar what other research teams had found before, antibodies don't seem to play an important role in controlling acute COVID-19. Instead, T cells and helper T cells in particular are associated with protective immune responses.
D Crotty added, "This was perplexing to many individuals but controlling a primary infection is not the same as vaccine-induced immunity, where the adaptive immune system is ready to pounce at time zero."
In the case of a successful vaccination, vaccine-induced antibodies are ready to intercept the virus when it shows up at the doorstep. In contrast, in a normal infection the virus gets a head start because the immune system has never seen anything like it. By the time the adaptive immune system is ready to go during a primary infection, the virus has already replicated inside cells and antibodies can't get to it.
Dr Crotty added, "Thus, these study findings indicate it is plausible T cells are more important in natural SARS-CoV-2 infection, and antibodies more important in a COVID-19 vaccine although it is also plausible that T cell responses against this virus are important in both cases."
The study team summarized their findings that the adaptive immune system has the capacity to cause immunopathogenesis. The team found little evidence to support hypotheses of pathogenic adaptive immune cells being causally involved in COVID-19 pathogenesis. Hospitalized COVID-19 patients did not have TH2 or TH17 cytokine skewed CD4+ T cell responses, consistent with most other reports .(Meckiff et al., 2020; Sekine et al., 2020; Weiskopf et al., 2020); and the CD8+ T cell response cytokine profile was similar between hospitalized and non-hospitalized cases.
The tam said that while they do not exclude the possibility of some functional T cell defects, the data here largely supported a model wherein a slow or uncoordinated (partial) adaptive immune response was associated with severe disease. Conversely, strong SARS-CoV-2-specific CD4+ or CD8+ T cell responses were associated with low disease severity.
The team’s adaptive immunity findings are consistent with findings that dysregulated innate immunity may be central to COVID-19 associated immunopathogenesis.
As COVID-19 vaccine development is a topic of major importance, the team says that a vaccine does not have to directly mimic protective immunity observed in natural infection, but should be informed by protective immunity observed in natural infection. Resolving an ongoing infection is more challenging than prophylaxis. The data presented in the study suggest that neutralizing antibodies play a role in resolving acute COVID-19, but statistical associations found less of a role for antibodies than SARS-CoV-2-specific CD4+ or CD8+ T cells.
These study results suggest that vaccine approaches that elicit antiviral SARS-CoV-2-specific CD4+ and CD8+ T cells in coordination with neutralizing antibodies will generate protective immunity that most closely analogous to the coordinated adaptive antiviral immune response seen in most cases of COVID-19 following natural SARS-CoV-2 infection.
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