Investigating the impact of antibodies against SARS-CoV-2 on the effectiveness of interleukin-6 inhibitors in Covid-19 patients

Numerous clinical trials have been carried out to find therapies against COVID-19. A great proportion of them has focused on patients admitted to hospital wards, or intensive care units.
Many drugs were tested in randomized clinical trials by different platforms and research groups. Some of the drugs belong to the therapeutic group of immunosuppressive agents. These molecules inhibit the immune system at different levels, or a precise point, modulating the dysregulated response of the immune system in COVID-19. So, these molecules bind to a protein and block its activity.
After numerous trials, a few molecules showed to improve the 28-days mortality. Among them, we pointed out the interleukin-6 (IL-6) inhibitors, mainly tocilizumab. Interleukin 6 is a cytokine (protein in the immune system) whose release may cause inflammation in excess.
The differences in mortality between the active therapy cohort comparing with the usual standard of care happened between the 2nd and 3rd week of diseases (around 16-18 days of symptoms onset). Considering previously published manuscripts, a novel, or not usually measured variable, could explain all these findings.
We propose the use of the individual's state of either having or not detectable antibodies against a specific protein of SARS-CoV-2, as measured by a blood test.
These individuals with a negative antibodies serum reaction against SARS-CoV-2 infection seems to be at a higher risk to a dysfunctional immune system response, and hence, to develop a pronunced inflammation and severe outcome in COVID-19. To check this hypothesis, we proposed to launch a posthoc analysis according to patient's blood serology (positive or negative) against SARS-CoV-2 infection. Our aim is to assess the differences between both cohorts of individuals in 28 days mortality and categorized them according to previously randomized cohorts in any clinical trial using IL-6 inhibitors.