People who have been infected with OC43, a common cold virus, may be at greater risk for developing Long COVID.

People who have been infected with OC43, a common cold virus, may be at greater risk for developing Long COVID.

What you need to know

One of the ongoing puzzles of the COVID-19 pandemic is understanding the causes and risk factors for Long COVID. A study funded by several NIH institutes found that previous infection with OC43, a coronavirus that causes the common cold, may increase the risk for Long COVID.

What did the researchers do?

The researchers enrolled participants with systemic autoimmune rheumatic disease who had had COVID-19. Systemic autoimmune rheumatic disease and other autoimmune diseases are chronic conditions where the immune system mistakenly targets the body’s own tissues to cause inflammation. When infected with SARS-CoV-2, nearly half of people with systemic autoimmune rheumatic disease develop symptoms of Long COVID.

The researchers divided their study population into people who did and did not develop Long COVID and compared the two groups’ antibody responses to SARS-CoV-2, other pathogens, and routine vaccines.

Compared with the non–Long COVID group, those who developed Long COVID had a much weaker antibody response to SARS-CoV-2. This group also showed a high antibody response to a coronavirus that causes the common cold, called OC43. Interestingly, a stronger response to OC43 correlated with a weaker response to SARS-CoV-2. This suggests that antibodies against OC43 may also be reacting to SARS-CoV-2.

Why is this research important?

This study shows how a person’s history of previous infections can affect their immune response to new infections. In this case, a person who was previously infected with OC43 developed antibodies. Their immune system then used the OC43 antibodies to target the SARS-CoV-2 infection, but this response was not strong enough and could have led to Long COVID.

These results explain why some people develop Long COVID. Further studies are needed to show whether this phenomenon occurs in people without autoimmune diseases, but this study provides an important clue to understanding some possible mechanisms behind Long COVID.

Where can I go to learn more?

Cold virus may set the stage for Long COVID

  • Research funded by several NIH institutes is focused on finding immune response risk factors associated with developing Long COVID.

Immune Response to COVID-19

  • The National Institute of Allergy and Infectious Diseases shares current research and efforts to understand the immune system’s response to COVID-19.

NCI COVID-19 Research Initiatives

  • Learn more about the National Cancer Institute’s research to address COVID-19, including immune responses to infection. 


Herman, J. D., Atyeo, C., Zur, Y., Cook, C. E., Patel, N. J., Vanni, K. M., Kowalski, E. N., Qian, G., Srivatsan, S., Shadick, N. A., Rao, D. A., Kellman, B., Mann, C. J., Lauffenburger, D., Wallace, Z. S., Sparks, J. A., & Alter, G. (2023). Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases. Science Translational Medicine, 15(712), eadf6598.


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Page last updated: November 2, 2023