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Multicenter Study
. 2025 Jan 7;15(1):e088486.
doi: 10.1136/bmjopen-2024-088486.

Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases

Melek Yalcin Mutlu  1   2 , Arnd Kleyer  1   2   3 , Gerhard Kroenke  1   2   3 , Filippo Fagni  1   2 , Selahattin Alp Temiz  1   2 , Christine Meder  2   4 , Peter Dietrich  5 , Till Orlemann  2   5 , Johanna Mößner  6 , Verena Schoenau  1   2 , Daniela Bohr  1   2 , Louis Schuster  1   2 , Fabian Hartmann  1   2 , Ioanna Minopoulou  1   2   3 , Moritz Leppkes  2   5 , Andreas Ramming  1   2 , Milena L Pachowsky  1   2 , Florian Schuch  7 , Monika Ronneberger  7 , Stefan Kleinert  7 , Axel J Hueber  1   8   9 , Karin Manger  1   10 , Bernhard Manger  1   2 , Raja Atreya  2   5 , Carola Berking  2   4 , Michael Sticherling  2   4 , Markus F Neurath  2   5 , Georg Schett  1   2 , David Simon #  1   2   3 , Koray Tascilar #  11   2
Affiliations
Multicenter Study

Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases

Melek Yalcin Mutlu et al. BMJ Open. .

Abstract

Objectives: Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design: A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

Setting: Seven tertiary regional care centers in Germany, which specialised in the care of patients with IMID (namely, in gastroenterology, dermatology, rheumatology and immunology clinical care).

Participants: One thousand nine hundred nine participants completed the survey (757 patients with IMID; 1152 non-IMID controls).

Primary outcome measure: The occurrence of 11 common viral illness symptoms within the preceding 3 months in patients with IMID and non-IMID controls.

Results: Symptom data were clustered, based on number and co-occurrance, into 3 major clusters and 2 subclusters ranked by the average number of symptoms. Patients with inflammatory bowel disease and psoriasis were significantly overrepresented in the lower-frequency subcluster of the polysymptomatic cluster. Patients with rheumatoid arthritis were overrepresented in the lower-frequency subclusters of the intermediate and oligo-/asymptomatic clusters. Controls were over-represented only in the higher-frequency subclusters of each major cluster where none of the IMIDs were over-represented. Spondyloarthritis and other IMIDs were also overrepresented in the low-frequency subcluster, but the results were not significant. Overall, patients with rheumatoid arthritis patients reported fewer symptoms (rate ratio=0.68, 95% CI, 0.59 to 0.80) than non-IMID controls.

Conclusion: Patients with IMID are over-represented in low-frequency subclusters, even among individuals who have reported a broad range of viral infection symptoms. This pattern suggests that the manifestations of viral infections are different between patients with IMID and controls, thus challenging the accurate and early diagnosis of infections.

Keywords: Respiratory infections; Rheumatology.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Cluster plot: Clusters according to symptom type and number. The most frequent symptom group was comprised of headache, pharyngitis and rhinitis, whereas the least frequent symptom group constituted shortness of breath, anosmia and fever (X-axis). Three major clusters, namely, polysymptomatic, intermediately symptomatic and oligo-/asymptomatic, were formed. Each cluster was divided into two subclusters showing higher and lower symptom frequencies (Y-axis).
Figure 2
Figure 2. Standardised residuals that summarise the difference between the observed and expected number of individuals in each cluster. Values <−2 or >2 were interpreted as an important deviation from the expected counts. Standardised residuals by diagnosis: Controls showed the largest positive deviations from the expected number of participants and over-represented in the high subcluster of each symptom frequency group. Conversely, patients with IMID predominated the low-symptom subclusters in each cluster. RA displayed the largest deviations. IBD, inflammatory bowel disease; IMID, immune-mediated inflammatory disease; RA, rheumatoid arthritis; SpA, spondyloarthritis.
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