Clearly, the immune system can elicit a robust response to SARS-CoV-2, as the vaccine trials have made clear. In addition, there are many question marks. People exposed to the virus do not always produce many antibodies against it, and there have been a number of cases of reinfection. We are not sure how long immunity lasts and whether it correlates with the antibody level or something else – there was not even good evidence that antibodies are useful.
To give an idea of the challenge of sorting it all out, let’s take a look at three recently published articles that come in the interaction between the immune system and COVID-19. One ultimately provides evidence that antibodies can be protective, and the other suggests that breaking down the inflammatory response may help, while the third suggests that immunosuppressants do not affect disease outcomes at all.
Antibodies good
Antibodies are a relatively easy way to detect an immune response, and are used throughout the pandemic. But early studies found that the number of antibodies produced in response to an infection differed dramatically between patients. Clinical trials have also been conducted to determine whether the use of antibodies obtained from those previously infected can help treat those suffering from COVID-19 symptoms, and the FDA will eventually grant a controversial authorization for emergency use. . President Trump also received an experimental treatment of mass-producing SARS-CoV-2-specific antibodies.
The strange thing about this is that we are not sure that antibodies are actually protective. Further trials of antibody treatments for those infected yielded ambiguous results, without having a clear advantage in obtaining an antibody boost. And although immunity levels in some studies appear to be related to the antibody levels, we can not be sure that the two are not both linked to another aspect of immune function – perhaps the antibody levels are merely a reflection of the activity of the T cell . an example.
A new article from researchers in Argentina is small, but it suggests that antibodies can help those with COVID-19 – but only if a treatment is given early enough. The research design is thorough: a randomized, blinded trial in which some people get a transfusion of saline solution, while others have had antibodies from those previously infected with their saline. Criticism is that all transfusions occurred within a few days after the onset of COVID-19 symptoms. The only limitation of the trial is that it took place while the case numbers in Argentina were falling, and so it was cut short once they had trouble recruiting patients.
Of the 160 patients who were all older than 65, 25 of the 80 in the control group had severe respiratory symptoms. In those who received the antibody-containing plasma, only 13 experienced these symptoms. The elimination of the six individuals who had to drop out of the study further improved the numbers. Finally, those who received plasma with the highest levels of antibodies tended to have an even better prognosis, although the number of patients here is even smaller.
Those who received the plasma also had less severe outcomes, such as admission to the ICU and need for ventilation. However, the numbers of each issue were all small, and none of these measures reached statistical significance.
The researchers note that those who received plasma treatments earlier in a few other studies tended to fare better, but the total population treated at different stages of the infection showed no effect. If it turns out to be right – and this study is small enough to really repeat it – it will provide the first clear evidence that antibodies are useful. This can not only be critical for the treatment of those who become infected, but also for detecting immunity and monitoring the risk in populations with different levels of vaccination.
Inflammation bad
The other lesson of the antibody study is that defining your treatment population – in this case newly symptomatic elderly – can be critical in identifying a clear effect, although it may be more difficult to find enough patients to conduct a thorough study. to do. That lesson may also apply to a draft manuscript describing a study of whether we can limit the effects of COVID-19 by lowering the inflammatory immune response. Studies of the genetics of COVID-19 patients have indicated that variations in some immune signaling molecules are associated with the severity of the disease. But studies of drugs that have blocked the effects of an inflammatory signaling molecule called interleukin-6 have shown no effect. The researchers suspected that this was because they accepted a wide range of patients.
So, to limit things, they started treating with interleukin-6 blockers as patients were admitted to the ICU. The trial enrolled about 800 people, about half of whom served as controls. The rest got one of two different inflammatory blockers. Among those who did not receive a drug, the mortality rate was about 36 percent. For those treated, however, the mortality rate was 27 percent.
It may not be a huge difference, but if it persists, it could make a significant difference in population-level survival. And the UK UK health service has already warned its doctors of the results as it begins re-evaluating these drugs.
Is the immune system overestimated?
All of this would apparently put the immune system at the center of the COVID-19 outcomes, which need not be the least bit surprising. But another study published this week raises questions about that. Here, researchers tracked the results of more than 2,000 COVID-19 cases that came through the Johns Hopkins medical system in March. Of these, more than 100 take drugs that are immunocompromised. And when the outcomes of the patients were analyzed, there was no noticeable difference between those who were immunocompromised and the rest of the population. The researchers measured mortality, length of stay, and need for ventilation, but none of them were significantly different.
It is important to emphasize that ‘immune suppression’ is not ‘incapable of eliciting any immune response’. But the response is generally quite limited.
What do you make of all this? The good news is that, if the results of the antibody continue, it indicates that antibodies can not only treat us for those at high risk for serious infection, but also an easy way to detect who is protecting in the future can be. The results are not really confused by the results with immunocompromised individuals, as antibodies are usually not produced during an initial infection unless it is delayed for a while (it takes a few weeks to appear at measurable levels).
In addition, however, things get very complicated. The immune system has multiple aspects (T-cell-based immunity, dendritic cells, innate immunity, etc.), and we do not really know how much of this is completely suppressed in individuals with immune weakening. If inflammation in some cases proves to be harmful, it is possible that some forms of immunosuppression may be helpful.
But the big picture that really drives these papers home is that the immune system as well as its interaction with this virus is extremely complicated. If a study does not have enough people to concentrate on specific patient populations or offer treatments at specific points during the infection, there is a chance that the main effects will be averaged. One problem is that at this stage there are many smaller, less focused studies that have already been published, leading to an incomplete and confused picture. Finally, there is undoubtedly a lot of variability between patient and patient that confuses things further.
All of this explains why there are so many confusing and seemingly contradictory publications. This reinforces the need to regard any outcome as conclusive. Over time, we will build a clearer picture of the course of a SARS-CoV-2 infection and the response of the immune system to it. However, given the time it will take, the focus will undoubtedly be on getting as many people vaccinated as quickly as possible.