Article Text

Prevalence, admission rates and hypoxia due to COVID-19 in patients with rheumatic disorders treated with targeted synthetic or biologic disease modifying antirheumatic drugs or methotrexate: a nationwide study from Iceland
  1. Aron Hjalti Bjornsson1,2,
  2. Gerdur Grondal3,
  3. Mar Kristjansson1,
  4. Thorunn Jonsdottir4,
  5. Thorvardur Jon Love2,
  6. Bjorn Gudbjornsson2,5
  1. 1 Medicine, National University Hospital of Iceland, Reykjavik, Iceland
  2. 2 Faculty of Medicine, University of Iceland School of Health Sciences, Reykjavik, Iceland
  3. 3 Rheumatology, National University Hospital of Iceland, Reykjavik, Capital, Iceland
  4. 4 Rheumatology, Landspítali University Hospital, Reykjavik, Iceland
  5. 5 Centre for Rheumatology Research, National University Hospital of Iceland, Reykjavik, Iceland
  1. Correspondence to Dr Aron Hjalti Bjornsson, Medicine, National University Hospital of Iceland, 101 Reykjavik, Iceland; aronh{at}

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Susceptibility and tolerance to COVID-19 of patients with rheumatic disorders remains poorly understood. A recent meta-analysis did not demonstrate any considerably worse outcomes.1 Sufferers from inflammatory rheumatic disorders are, however, known to be more prone to infections than the general population and this risk is increased by targeted biologic therapy.2 3 Therefore, we were interested in examining the risk of admission and respiratory failure in patients with rheumatic disorders with COVID-19 being treated with targeted synthetic or biologic disease-modifying anti-rheumatic drugs (ts/bDMARDs), comparing them to matched comparators and methotrexate (MTX) users within Iceland. Unique conditions exist in Iceland for this study, as the island nation is naturally isolated and performed extensive screening, tracing and systematic registration of all PCR-confirmed cases.4 5 All diagnosed individuals received regular follow-up by a COVID-19 outpatient clinic.6

ICEBIO is a nationwide registry of patients with inflammatory arthritis treated with ts/bDMARDs. We included all patients in ICEBIO undergoing treatment at the start of the domestic outbreak. From the Icelandic Medicine Database we extracted all MTX prescriptions filled in the 9 months before Iceland’s first recorded case of COVID-19. Each individual from the ICEBIO and MTX groups was randomly matched with up to ten controls based on age, sex and geographic location. Individuals in ICEBIO or with MTX prescriptions from haematologists and oncologists were excluded from the MTX group, although their comparator group remained unaltered. The Icelandic Directorate of Health provided data on all PCR tests and hospital admissions in our study population. Data were extracted on 3 June 2020, when the first domestic outbreak ended: 1796 individuals had been diagnosed with COVID-19, with two active cases remaining. At that time, 61 639 tests had been administered in a nation of roughly 360 000 people, and the Directorate of Health reports a successful infection tracing rate of over 95%.4

We identified 1438 individuals from ICEBIO, 13 815 ICEBIO comparators, 1746 individuals with an MTX prescription and 22 962 MTX comparators, see table 1. The relative risk (RR) for the ICEBIO group to undergo testing was 1.35 (1.23–1.48; p<0.001), compared with their comparators and the RR for the MTX group at 1.05 (0.96–1.15; p=0.28) compared with theirs.

Table 1

Demographics, proportion and the number of individuals who underwent nasal swab PCR test for SARS-CoV-2; numbers of hospital admission and prevalence of COVID-19 in studied groups

Nine from ICEBIO, eighty-four ICEBIO comparators, five MTX treated and one hundred and thirty-four MTX comparators were SARS-CoV-2 positive. All infected patients from ICEBIO had received tumour necrosis factor inhibitors (online supplemental tables S1 and S2). Two of three hospitalised patients from ICEBIO, three of three ICEBIO comparators, one of one from the MTX group and ten of thirteen hospitalised MTX comparators received oxygen supplementation. One of three admitted patients from the ICEBIO comparators and two of thirteen MTX comparators received mechanical ventilation (table 1). The RR for infected patients from ICEBIO to be admitted was 9.33 (2.20–39.6; p<0.001) and 6.22 (1.19–32.46; p=0.02) to be admitted with hypoxia. The RR for hypoxia following admission was 0.67 (0.30–1.48) for patients from ICEBIO and 0.77 (0.57–1.4) for patients taking MTX. The mean length of admission for the patient from ICEBIO was 4.7±3.6 days, while it was 20.2±12.7 days for their comparators (p=0.16). As no patients with rheumatic disorders in any group required mechanical ventilation, neither OR nor RR can be calculated for that outcome.

We found that patients with COVID-19 with rheumatologic disorders on bDMARDs are at a higher risk of hospitalisation than matched comparators. This might be explained by a lower threshold for admitting patients on biologics, as hospitalised rheumatology patients on bDMARDs fared numerically better, although the small numbers prevent meaningful statistical analysis. Further studies in larger populations are needed to better quantify the risk and severity of COVID-19 in patients with rheumatic disorders treated with bDMARDs.

Ethics statements

Ethics approval

The study protocol was accepted by the National Bioethics Committee and the Data Protective Authority in Iceland (License no: VSNb2020040014).


The authors thank all patients who record their symptoms on a regular basis in ICEBIO and to all rheumatologists in Iceland who are part of the ICEBIO group. The authors also extend their gratitude to Mrs Ingibjörg Richter for data extraction from the COVID-19 and Hospital Admission Registries.


Supplementary materials

  • Supplementary Data

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  • Handling editor Josef S Smolen

  • Collaborators ICEBIO group: Kristjan Erlendsson, Arni J Geirsson, Helgi Jonsson, Bjorn R Ludviksson, Gudrun B Reynisdottir, Kristjan Steinsson, Saedis Saevarsdottir, Gunnar Tomasson, Arnor Vikingsson.

  • Contributors AHB, TJL and BG designed and drafted the work, with analysis and interpretation of data, revising it critically for important intellectual content. All coauthors made substantial contributions to the study design, revised and approved the version to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.