Respiratory viral infections may be a novel environmental factor that contributes to the development of rheumatoid arthritis (RA), particularly in women and the elderly, according to research published in Arthritis Research and Therapy.

After identifying patterns of incident RA in the South Korean population, researchers conducted a time-series analysis to investigate the associations between the detection rate of ambient respiratory viral infections and cases of incident RA.

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The ecological study design relied on records from the Korean National Health Insurance database from 2011 to 2015. Included individuals were 19 years or older with RA-related claims data with a prescription for a disease-modifying antirheumatic drug and 3 consecutive years of treatment.

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Between 2012 and 2013, 24,117 patients were newly diagnosed with RA; 77.5% of these cases were in women, with a mean age at diagnosis of 54.7±13.2 years. Nearly all patients had access to national health insurance (95%).

Investigators found a seasonal tendency in incident RA diagnoses, with an increase in incident RA from January to July 2012 (781 cases to 1274 cases) and a decrease from July to December (775 cases). A similar pattern of seasonality was noted in 2013 (from 1057 cases to 1212 cases from January to July and 853 cases in December). In both years, a significantly lower number of weekly incident RA cases was noted from September to February. These seasonal patterns were similar in both men and women.

Similarly, respiratory viral infections demonstrated seasonal tendencies in 2012 and 2013. Parainfluenza and bocavirus outbreaks tended to occur in late spring and early summer, whereas respiratory syncytial virus tended to be diagnosed in autumn. Influenza outbreaks were common during the winter, and coronavirus was diagnosed most often between November and December. Rhinovirus was most prevalent from spring to autumn, whereas metapneumovirus was infrequent but was most often diagnosed in late winter and spring.

When examining the association between respiratory viral infection rates and incident RA cases, fluctuations in associations were observed for all viruses except for bocavirus. As the lag structure for each virus changed, fluctuations in associations disappeared, and the association between viral infection and incident RA became more apparent.

In particular, parainfluenza, coronavirus, and metapneumovirus were most associated with incident RA, according to a time-series analysis. Incident RA increased by 4.8% in cases of parainfluenza, 9.2% for coronavirus, and 44% for metapneumovirus, with an incremental 1% increase in virus detection rate.

Subgroup analysis results found that all 3 viruses were significantly associated with incident RA in women; in men, only parainfluenza virus was associated with incident RA. Additionally, early onset RA was significantly associated with all 3 viruses, but only parainfluenza was significantly associated with incident RA in patients 40 years or younger.

Limitations to the study included the investigators’ inability to prove a causal association between ambient respiratory viral infections and incident RA due to the ecological nature of the study.

“These results support the etiological hypothesis that respiratory viral infections in the population may have the capacity to trigger RA,” the researchers concluded. “Further study including all patients with acute respiratory infection symptoms, not based on [polymerase chain reaction], confirmed infection would also be valuable when investigating possible associations between respiratory infections and RA development.”


Joo YB, Lim YH, Kim KJ, Park KS, Park YJ. Respiratory viral infections and the risk of rheumatoid arthritis. Arthritis Res Ther. 2019;21(1):199.

This article originally appeared on Rheumatology Advisor