Antibodies in patients with severe COVID-19 suffer a striking decline in their ability to control inflammation – a change that can be identified with a glycan biomarker.
New research could pave the way for the development of glycan biomarkers in COVID-19 disease severity detection.
A newly-published research study has compared blood samples of COVID-19 patients over the course of several weeks and found that in the severe cases, disruptive change in the glycan profile involved in the regulation of Immunoglobulin G (IgG) occurred days after falling ill, while IgG glycans of mild cases remained unchanged .
Longevity.Technology: SARS-CoV-2, the virus responsible for the COVID-19 outbreak, caused over 6 million deaths worldwide. This virus is infamous for its capabilities to evade immune surveillance and cause severe or prolonged disease. One of the main factors accounting for the “success” of the SARS-CoV-2 (other than its unprecedented infectivity) is the fact that the vast majority of the infected individuals suffer only mild symptoms or even remain asymptomatic facilitating the transmission to those that can suffer deadly consequences.
Though many of the risk factors for the severity of the disease have been identified, such as advanced age, diabetes, &c, it is not unusual for the individuals without any of the risk factors to fall severely ill or even die. This is precisely why identifying early biomarkers of disease severity has been key in efforts to end the social and health effects of COVID-19.
The need for disease management and deeper understanding of mechanisms causing COVID-19 severity resulted in the unprecedented race for knowledge. The most recent addition to the body of papers generated over the last two years presented a possible new biomarker of COVID-19 severity: IgG glycans.
Glycans are complex sugar molecules, and as one of the four basic molecules of life, they can be found not only attached to the exterior surfaces of nearly all cells, but on a vast majority of the molecules circulating throughout our body. One of the molecules that requires glycans for its function within the immune system is Immunoglobulin G (IgG), the most prevalent antibody in our blood.
It is normal for our IgG glycans to become pro-inflammatory as we age, and this natural process has been recognised as a glycan clock, driving the biological aging. However, glycosylation changes are also essential for response to pathogens – a simple change of the glycan attached to IgG can modulate inflammatory response and allow the virus to escape our immune system. Therefore, it is not surprising that several studies looked at the IgG glycosylation in the context of COVID-19 infection. However, this is the first longitudinal study comparing the mild and severe COVID-19 cases over the course of several weeks after falling ill .
Scientists from GENOS Glycoscience research laboratory, the biggest high-throughput laboratory for glycan analysis in the world, identified 158 patients from several hospitals in whom COVID-19 was a main cause of the disease, and then followed for up to one month 108 patients with severe COVID-19 as well as 48 patients with mild or asymptomatic COVID-19.
In severe COVID-19 patients, the pro-inflammatory alteration of IgG glycome stimulated the loss of immunosuppressive effect of IgG that might play a mechanistic role in the disease severity (Figure1).
This is the first published proof that acute SARS-CoV-2 infection can cause striking changes in the total IgG glycome within several days . As the authors note, interestingly, some of the same pro-inflammatory changes observed in this paper also occur during biological aging, but while the pro-inflammatory change of IgG glycans naturally occurs over years or decades, severe COVID causes “rapid aging” in weeks.
Since the IgG glycan biomarker has already been in use for years for the purpose of measuring biological aging, this latest finding paves the way for swift development and adoption of a potential glycan biomarker of COVID-19 disease severity.
Gordan Lauc, PhD, Founder and CSO of GlycanAge told Longevity.Technology that glycans are the ultimate level of molecular complexity that is essential not only in virtually all major diseases, but also healthy aging.
“We still do not understand many aspects of aging at the molecular level, but we know that there are things that can accelerate, slow down, or even revert aging at the molecular level,” he explained. “GlycanAge is based on glycans attached to immunoglobulins and is in this respect particularly relevant to processes that include regulation of the immune system.
“Viral infections are a great challenge to our immune system and unfortunately not all of us can successfully recover from viral infections, as we have witnessed in this pandemic. Glycans are responsible for many aspects of inter-individual variability, and we see this also in covid. Our initial study published in November 2020 demonstrated that IgG glycans can predict disease severity better than chronological age. In this large longitudinal study we showed that severe covid also causes rapid acceleration of biological age, with some of the key components of the GlycanAge index changing for 30-40% within 2-3 weeks. At the same time, mild and asymptomatic covid did not cause any changes. While we still do not understand all aspects of this rapid acceleration in biological age, it is certainly worrying and indicates the need for further studies.”