The SARS-CoV-2 virus and the associated COVID-19 disease remain significant global health threats. Since the emergence of SARS-CoV-2 at the end of 2019, much has been learned about its infection course, including transmission, replication, and immune reactivity. Findings of a new report demonstrate the effects of previous infection with the common cold virus on the course of SARS-CoV-2 infection.

The SARS-CoV-2 virus first enters the upper respiratory tract (i.e., the nasopharynx) via the angiotensin-converting enzyme (ACE) 2 receptor and replicates in epithelial tissue, peaking in concentration within one week of infection. The amount of viral replication in the early stages of infection determines transmissibility and predicts the severity of COVID-19 illness. As the number of viral particles increases, the immune system enhances the expression of interferon-stimulated genes, which are necessary for the antiviral response. People who have had a recent viral infection, such as the common cold, may have greater interferon-stimulated gene expression at the time of SARS-CoV-2 infection, limiting viral replication.

The researchers used nasopharyngeal swabs from 170 patients with a confirmed SARS-CoV-2 infection and eight healthcare workers who did not have an infection. The researchers used swabs from multiple time points to monitor infection progression, including viral replication and immune response. They obtained information regarding previous viral infections, health history, and COVID-19 status from medical records. In a second experiment, the researchers exposed in vitro human bronchial epithelial cells to rhinovirus, which causes the common cold, before exposure to the SARS-CoV-2 virus to determine the effects of previous infection on immunity.

The authors found that the SARS-CoV-2 virus elicits increased expression of interferon-stimulated genes after four days of replication similar to other viral infections. Participants with the highest concentration of the protein CXCL10 (a proxy for interferon-stimulated gene expression) were less likely to require hospitalization but had a higher concentration of viral particles in their nasopharynx. The authors posited that patients in the hospital had likely been sick for a longer period of time and had passed the point of infection when viral replication and interferon-stimulated gene expression are highest. In vitro cells that had been previously infected with rhinovirus increased their expression of interferon-stimulated genes, including the short version of the ACE2 receptor. Unlike the long version, SARS-CoV-2 cannot enter through the short ACE2 receptor, meaning that previous rhinovirus infection prevents SARS-CoV-2 entry and dampens viral replication.

These findings demonstrate that previous infection with rhinovirus decreases the risk of contracting the SARS-CoV-2 virus and may decrease the severity of COVID-19 disease.

• Link to full report.