Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Although many genes have polymorphisms, major histocompatibility complex genes are the most polymorphic. Many assume that the diversity of HLA increases the likelihood that a species can survive pandemics. Indeed, evidence suggests that HLA-B27 is protective for HIV1, hepatitis C2, and possibly influenza3.
HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject’s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p < 0.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.
Objective The Covid-19 pandemic has created multiple uncertainties regarding rheumatic diseases or their treatment and susceptibility or severity of the viral disease. Methods To address these questions as they relate to spondyloarthritis, we created a longitudinal survey from April 10, 2020 to April 26, 2021. 4723 world-wide subjects with spondyloarthritis and 450 household contacts participated. 3064 of the respondents were from the US and 70.4% of them provided longitudinal data. To control for the duration of potential risk of Covid-19, the rate of contracting Covid-19 was normalized for person months of exposure. Results In an analysis of US subjects who provided longitudinal data, the incident rate ratio for the 159 (out of 2157) subjects who tested positive for Covid-19 was 1.16 compared to the US population as adjusted for age and sex (range 0.997 to 1.361, p=0.059). A paired evaluation using patients and household members did not show a statistically significant effect to indicate a predisposition to develop Covid-19 as a result of spondyloarthritis or its treatment. Our data failed to show that any class of medication commonly used to treat spondyloarthritis significantly affected the risk to develop Covid-19 or the severity of Covid-19. Conclusion These data do not exclude a small increased risk to develop Covid-19 as a result of spondyloarthritis, but the risk, if it exists, is low and not consistently demonstrated. The data should provide reassurance to patients and to rheumatologists about the risk that Covid-19 poses to patients with spondyloarthritis.
Medications are based on information from the most recent survey or at the time of developing COVID-19. Patients could be taking more than one medication. *P value determined by Wald's test.
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