A prior common cold infection can combat COVID-19: Scientists

Scientists have found out that the common cold infection can fire up the immune system to produce early response immunity molecules that can halt SARS-CoV-2 virus replication

Before the reign of COVID-19, viruses such as the influenza virus and the rhinovirus were the perpetrators of many respiratory issues such as the flu and common cold. However, the incidence of flu infections has reduced during the COVID-19 pandemic. This could be attributed to reduced interactions with one another, continuous hand washing, heightened sanitiser use and wearing masks. 

The rhinovirus is a small RNA virus that replicates at 33-35℃ (the temperature of the nasal region) and causes allergic rhinitis or common cold. These infections are rapid in nature as the virus adheres to the respiratory surface within 15 minutes of entry. Rhinoviruses can trigger several protective immune cytokine pathways including that of interferons. Interferons are antiviral molecules involved in innate as well as adaptive immunity. The interferons amplify the expression of Interferon Stimulated Genes (ISG) which can further trigger antiviral responses. The kinetics and magnitude of the interferon responses vary from virus to virus.

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SARS-CoV-2 primarily replicates in the upper respiratory tract and the viral load peaks within the first week of infection. Innate immune responses are the first line of defence against any kind of infection. The Innate Interferon response can curtail the replication of the virus in the mucosal cavity. However, SARS-CoV-2, through the viral RNA sensor MDA5, sets off the delayed production of interferons and ISGs which is ineffective in clearing out the viral load. 

Ellen Foxman and her team at the Yale School of Medicine went to understand the dynamics of interferons and ISGs in a SARS-CoV-2 infection by analysing the RNA from nasal swabs.  They also went on to study how a rhinovirus infection is capable of protecting the respiratory cells from SARS-CoV-2 damage. The results of this study were published in the Journal of Experimental Medicine. 

The research team first wanted to define the host-pathogen interactions between the SARS-CoV-2 virus and the immune system. Using the nasal swabs from various SARS-CoV-2 infected patients, they did RNA sequencing to estimate the viral load. They observed that higher interferon and ISG levels were associated with higher viral load. Although several of the interferon molecules are involved in clearing out the viral load, the scientists used one particular molecule, CXCL10 as the biomarker to correlate with interferon activity. SARS-CoV-2 induced a robust interferon response in the respiratory region and that the CXCL10 protein level correlated with ISG expression at the RNA level.

The scientists further did their testing on human airway epithelial cells that differentiated to look like the respiratory airway (organoid) that produces mucus and had respiratory cilia (nasal hair). On infecting these organoids with the SARS-CoV-2 virus they even found out that the virus grew in an exponential manner. Although viruses do not follow an exponential type of growth, SARS-CoV-2 doubled in population every six hours and produced a sustained interferon response 4 days post-infection. 

The team then infected the organoids with rhinovirus. This virus increased the expression of several relevant interferons as well as CXCL10 and the overall ACE-2 receptor activation. These responses were seen within three days of rhinovirus infection, after which the organoids looked like a normal respiratory airway indicating that the infection cleared out. When these rhinovirus primed organoids were infected with SARS-CoV-2, there was no increase in the coronavirus load as compared to the non-rhinovirus infected organoids where the SARS-CoV-2 levels were high. The interferon and ISG responses that were triggered by the rhinovirus were capable of keeping the SARS-CoV-2 infection at bay. 

The scientists then lowered the expression of the ISG genes and blocked the interferon activity in these organoids. Even with prior rhinovirus infection, SARS-CoV-2 went on to multiply at a high rate as there were no interferons to restrict viral replication. The presence of an intact host antiviral machinery is essential to curtail virus infections. 

This study was successful in establishing the primary stages of the host-pathogen interaction that takes place in SARS-CoV-2 infections. These results illustrate the importance of interferons in curbing SARS-CoV-2 replication at the start of infection, including innate immune responses induced by prior rhinovirus infection. The key takeaway from this study is that the airway innate immune response is dynamic and adapts to the changing external viral environment. 

“There are hidden interactions between viruses that we don’t quite understand, and these findings are a piece of the puzzle we are just now looking at,” assert the researchers.  

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