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COVID-19 and how evidence of a new disease evolves
  1. Féline P B Kroon1,2,
  2. Ted R Mikuls3,
  3. Robert BM Landewé1,4
  1. 1 Rheumatology, Zuyderland Medical Centre, Heerlen, The Netherlands
  2. 2 Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
  4. 4 Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands
  1. Correspondence to Féline P B Kroon, Zuyderland Medical Centre Heerlen, Heerlen 6419 PC, The Netherlands; f.kroon.reum{at}

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In 7 months’ time, COVID-19 has developed from a single case to a pandemic affecting more than nine million people worldwide, and the outlook of many more to come. While the majority fare a mild disease course, the world has seen large numbers of critically ill and deaths. These are unprecedented times, in modern history only comparable to the 1918 Spanish influenza,1 as we are faced by the worldwide spread of a disease that was non-existent less than a year ago.

‘Evidence-based medicine’ is proudly rooted in our practice nowadays and also expected to provide us with guidance on how to respond to COVID-19. As a result, the number of studies on COVID-19 is increasing exponentially. The accumulating data are widely available owing to the ‘digital era’ we live in, which, despite obvious advantages of public availability of information, also poses risks of ‘information overload’ or ‘fake news’.

The rapid increase in research on COVID-19 is encouraging, yet, it is important to realise what these published data entail. For example, the discussion whether hydroxychloroquine is effective and safe in the treatment of COVID-19, nicely outlined by Kim et al,2 3 and the recent retraction by major journals of two of their papers that were based on large but unreliable data repositories, illustrate why it is important to carefully interpret literature that is being published and the large societal consequences this interpretation may have. To accommodate the demand for guidance from patients and clinicians, also within the field of rheumatology, recommendations are issued by groups of the so-called experts and (inter)national societies, such as, among others, American College of Rheumatology4 and European League Against Rheumatism5 have done. Traditionally, such recommendations are evidence based, but what evidence can recommendations for COVID-19 be based on?

A PubMed search for available evidence on COVID-19 in the context of rheumatic and musculoskeletal diseases (RMDs) from 1 January 2019 until 24 June 2020, using search terms encompassing COVID-19, RMDs and drugs used in RMDs, generates 1725 hits. The exponential increase in publications over time is evident (figure 1). However, the majority (60%) are viewpoints or (narrative) literature reviews, and only a small proportion actually presents original data in the form of case reports or case series (15%), observational cohort studies (10%) or clinical trials (<1%). Moreover, most studies focus on drugs used in the field of rheumatology and their putative ability to treat COVID-19; roughly 10% is specific to COVID-19 in the context of RMDs. Of these, again, only 20% presents any original data (case reports, case series or observational cohort studies).

Figure 1

Cumulative number of hits in PubMed from 1 January 2019, using search terms encompassing COVID-19, rheumatic and musculoskeletal diseases (RMDs) and drugs used to treat RMDs.

While case reports are generally appreciated to yield only low levels of evidence, limitations of cohort studies on COVID-19 in RMDs should not be overlooked. Even in well-established registries or large cohorts with extensive correction for confounders, selection bias can hardly be eliminated and may lead to spurious associations. While traditionally seen as conveying the highest level of evidence, systematic literature reviews (SLRs) or meta-analyses of these studies, which will undoubtedly appear more frequently in the next few months in response to requests by users who feel overwhelmed by a multitude of data, will not eliminate the internal bias present in individual studies (an SLR does not whitewash the biases in inferior studies).

In conclusion, while evidence on COVID-19 evolves at an enormously rapid pace, the sheer number of studies is no measure for the quality of the data presented. To date, no robust evidence is available to allow strong conclusions on the effects of COVID-19 in patients with RMDs or whether RMDs or its treatment impact incidence of infection or outcomes. As researchers and clinicians, it is our responsibility to carefully interpret study results that emerge, even more so in this ‘digital era’, in which published data can quickly have a large societal impact.



  • Handling editor Josef S Smolen

  • Contributors All authors contributed equally to the manuscript and approved of the final version.

  • 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.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

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