Clearly, the immune system can build a robust response to SARS-CoV-2, as the vaccine studies have shown. But besides that there are many question marks. People exposed to the virus don’t always produce many antibodies to the virus, and there have been a number of cases of reinfection. We’re not sure how long immunity lasts or if it correlates with antibody levels or anything else – there’s not even great evidence that antibodies are helpful.
To give some idea of the challenge of getting all of this together, let’s look at three recently published articles on the interaction between the immune system and COVID-19. Finally, one provides some evidence that antibodies may be protective, another indicates that reducing the inflammatory response may help, while the third suggests that immunosuppressants do not affect the outcomes of the disease at all.
Antibodies good
Antibodies are a relatively easy way to detect an immune response, and they have been used to do so during the pandemic. But early studies found that the number of antibodies produced in response to infection varied significantly between patients. There have also been clinical trials to test whether the use of antibodies obtained from previously infected individuals could help treat people with COVID-19 symptoms, with the FDA eventually granting it a controversial Emergency Use Authorization. President Trump also received experimental treatment of mass-produced SARS-CoV-2 specific antibodies.
The strange thing about this is that we are not sure whether antibodies are really protective. Further trials of antibody treatments for infected individuals have yielded ambiguous results, with no apparent benefit from receiving an antibody boost. And while immunity levels seem to correlate with antibody levels in some studies, we can’t be sure that the two aren’t both related to a different aspect of immune function – perhaps antibody levels are just a reflection of T cell activity, to give an example. .
A new paper from researchers in Argentina is small, but it indicates that antibodies can help people with COVID-19 – but only if a treatment is given early enough. The study design is solid: a randomized, blinded trial in which some people received a saline transfusion, while others had antibodies from those previously contaminated with their saline solution. It is critical that all transfusions occurred within a few days of the onset of COVID-19 symptoms. The only limitation to the process is that it took place while the number of cases in Argentina was declining, so it was cut short when they had trouble recruiting patients.
Of the 160 patients, all older than 65 years, who were enrolled, 25 of the 80 in the control group developed serious respiratory complaints. Of those who received the antibody-containing plasma, only 13 experienced these symptoms. By eliminating the six individuals who had to drop out of the study, the numbers were further improved. Finally, those who got plasma with the highest levels of antibodies in it tended to have an even better prognosis, although the number of patients here is even smaller.
Those who received the plasma also had less serious consequences, such as admission to the ICU and need for ventilation. However, the numbers of each individual problem were all small, so none of these measures reached statistical significance.
The researchers note that in a few other studies, those who received plasma treatments early fared better, but the overall population treated at different stages of the infection showed no effect. If this turns out to be correct – and this study is small enough to be truly replicated – it would provide the first clear evidence that antibodies are useful. This can be critical not only for treating those who become infected, but also for detecting immunity and monitoring risk in populations with different vaccination levels.
Ignition bad
The other lesson of antibody research is that carefully defining your treated population – in this case, only symptomatic elderly – can be critical to identifying a clear effect, even though it may become more difficult to find enough patients for a thorough research. That lesson could also apply to a draft manuscript examining whether we can limit the effects of COVID-19 by reducing the inflammatory immune response. Studies of the genetics of COVID-19 patients had shown that variations in some immune signaling molecules were related to disease severity. But studies of drugs that blocked the effects of an inflammatory signaling molecule called interleukin-6 had shown no effect. The researchers suspected this was because they accepted a wide variety of patients.
So to narrow things down, they started treatments with the interleukin 6 blockers when patients were admitted to the ICU. About 800 people took part in the trial, about half of whom served as controls. The remainder received one of two different anti-inflammatories. Among those who did not receive medication, the death rate was about 36 percent. Among those treated, the death rate was 27 percent.
That may not be a huge difference, but if it holds up, it can make a significant difference in survival at the population level. And the UK’s National Health Service has already notified its doctors of the results as it begins a re-evaluation of these drugs.
Is the immune system overrated?
All of this would seemingly put the immune system at the center of the COVID-19 results, which should be by no means surprising. But another study published this week raises questions even about that. Here, researchers tracked the results of more than 2,000 COVID-19 cases that entered through the Johns Hopkins medical system in March. Of these, more than 100 were on drugs that made them immunocompromised. And when the patients’ outcomes 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 “immunosuppression” does not mean “being unable to elicit an immune response.” But the response is generally quite limited.
What should you make of this? The good news is, if the antibody results persist, they indicate that antibodies can not only provide us with a therapy for those at high risk of serious infection, but also an easy way to track who may be protected in the future. will be. Those results aren’t really confused by the results with immunocompromised individuals, as antibodies aren’t typically produced during an initial infection unless it persists for a while (it takes a few weeks for them to show up at measurable levels).
Apart from that, however, things get very complicated. The immune system has multiple aspects (T cell-based immunity, dendritic cells, innate immunity, etc.), and we don’t really know how many of these were completely suppressed in the immunocompromised individuals. If inflammation turns out to be harmful in some cases, it is possible that some forms of immunosuppression can actually help.
But the big picture these papers really bring home is that both the immune system and interactions with this virus are extraordinarily complex. If a study does not have enough people to focus on specific patient populations, or to deliver treatments at specific points during the infection, there is a chance that important effects will be averaged out. One problem is that at this point we have already published much smaller, less focused studies, which leads to an incomplete and confused picture. Finally, there is no doubt a lot of patient-to-patient variability that further confuses things.
All of this explains why there are so many confusing and seemingly contradictory publications. It reinforces the need to treat each individual result as convincing. Over time, we will gain a clearer picture of the course of SARS-CoV-2 infection and the immune system’s response to it. Given the time it will take, the focus will undoubtedly be on rushing to get as many people vaccinated as soon as possible.