Study suggests recent common cold may actually lead to worse COVID-19 disease

By Dr. Tomislav Meštrović, MD, Ph.D.Mar 8 2022Reviewed by Aimee Molineux

A new study published in the Journal of Infectious Diseases shines an unexpected light on the notion that pre-existing immunity to common cold coronaviruses can protect us from coronavirus disease 2019 (COVID-19) – and reveals that this may actually put certain individuals at risk of more severe clinical presentations.

Study: IgG Against Human β-Coronavirus Spike Proteins Correlates with SARS-CoV-2 anti-Spike IgG Responses and COVID-19 Disease Severity. ​​​​​​​Image Credit: NIAID

Most individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the ongoing COVID-19 pandemic, have only mild symptoms; however, some quickly develop severe pneumonia and other respiratory problems associated with high death rates.

This means understanding immunity against this virus is pivotal to developing adequate treatment approaches and salient vaccine strategies, which is why we often turn our attention towards the two most immuno-dominant antigens – spike glycoprotein (a structure on the cell surface that aids in infection) and nucleocapsid viral protein antigens.

We know that SARS-CoV-2 is part of a big family of viruses that predominantly cause the common cold, but all constituents share certain structural traits. Accordingly, many studies have found that previous infections with such viruses can protect the host from the severe COVID-19 manifestations.

Conversely, other research groups report that immune imprinting to conserved epitopes of seasonal human coronaviruses is negatively correlated with the induction of humoral immune response (i.e., IgG and IgM antibodies) against the SARS-CoV-2 spike glycoprotein.

This study, led by Dr. Jiong Wang and Dr. Martin S. Zand from the University of Rochester Medical Center in the US, aimed to improve our understanding on the effect of pre-existing humoral responses against human coronavirus that cause common cold on the pathogenesis of SARS-CoV-2 infection.

From blood samples to immune response insights

In this paper, immunity to various coronaviruses – including the SARS-CoV-2 virus – has been examined in blood samples taken from 155 patients who developed COVID-19 during the early months of the pandemic.

Of those patients, 112 have been hospitalized and provided sequential samples over the course of their hospitalization, when a rapid and significant increase in antibodies targeting SARS-CoV-2 and several other coronaviruses has been observed.

Moreover, the study also appraised 188 blood samples taken in the pre-COVID era (i.e., prior to December 2019) as controls. This group also included sera that might create false-positive reactions for anti-SARS-CoV-2 spike glycoprotein reactivity.

A type of 'immune distraction'

And while an increase in antibody quantity is usually a good thing as it shows protective proteins generated by the immune system, in this case this was not favorable. More specifically, the study has shown that antibodies were indeed targeting parts of the spike glycoprotein of SARS-CoV-2 similar to common cold coronaviruses.

However, these antibodies stemmed from immune memory and actually targeted areas that could not lead to the SARS-CoV-2 neutralization effect, which can be viewed as a type of 'immune distraction.' In other words, when these antibody levels rose faster than actual SARS-CoV-2 neutralizing antibodies, this translated to worse disease outcomes and an increased chance of death.

Thus, this is another addition to the growing pool of evidence that a phenomenon known as 'immune imprinting' is seen in COVID-19 immune responses. Previously, this has been associated with inadequate immune responses to other viruses (such as influenza), with potential implications for our vaccine strategies.

Implications for vaccine strategies

Experts are slowly agreeing that COVID-19 will likely be with us for a long time, with the emergence of novel milder strains that circulate on an annual or seasonal basis. This means that new vaccines targeting those new strains will have to be developed on a regular basis.

"We should expect that development of new vaccines is a good thing", said Dr. Martin S. Zand in this paper recently published in the Journal of Infectious Diseases.

"It doesn't mean the original science was wrong. It means nature has changed. If we want an immune system that pays attention to the right stuff, we need to teach it new tricks with different vaccines", he adds.

In any case, this is undoubtedly an intriguing finding, which should be further explored by a future analysis with much more longitudinal data, as there are direct implications for our public health strategies.