• What was it that urged you to do this study?
  Before the onset of the pandemic it was already well established that patients with rheumatoid arthritis (RA) have a higher prevalence of various respiratory conditions and an increased risk of infection. We thought therefore it was important to investigate if an infection with SARS-CoV2, a virus associated with potentially severe or fatal respiratory infection in the general population, inflicted a further increased risk of infections, severe infections, and increased mortality in patients with RA. At the stage of the pandemic where the COVID-19-vaccinations came into play, we thought it is important to revisit this topic, not only from a clinical and academic interest, but also to potentially provide scientific documentation to the health authorities and politicians for future prioritizations of (re-)vaccinations against SARS-CoV2.
• What was the most surprising outcome of this study?
  We were positively surprised by the extent to which the absolute risk of being hospitalized with COVID-19 decreased after the second dose of COVID-19-vaccine. The decrease was seen in patients with RA as well as in their age- and gender-matched controls. During the study period, individuals were considered to be fully vaccinated once they had received their second dose (this was before Omicron entered the stage). We do acknowledge that the decrease in the absolute risk was in part also due to other factors such as seasonal effects and impact of social distancing measures. Even so, the decrease was significant.
• Which measures did rheumatologists take in Denmark about how care of rheumatology patients needed to be adjusted during the pandemic?
  This is an interesting question, and although it falls outside the scope of our study, I think one general observations was that there was a strict adherence to general national and regional COVID-19 guidelines for outpatient care. This meant that measures of telemedicine, app- and web-based solutions were prioritized higher. Data from DANBIO (A registry in Denmark where all adult rheumatological patients are recorded) supporting this statement would include the observation that there were fewer DMARD treatment starts registered in 2020, and the number of outpatient visits were lower in 2020 and 2021 than in previous years.
• Why do you think the absolute risk was low in the study? Is this a Danish phenomenon – could you elaborate on the reason?
  The debate around the right way of handling the COVID-19 pandemic on a societal level is, to some extent, still ongoing. However, there’s no doubt that even within Europe, the various countries had very different approaches and means with which to deal with the pandemic. Compared to most of or many of our neighboring countries, Denmark had lower incidence rates of COVID-19 admissions and COVID-19 related deaths, and we don’t have any reason to believe that the number of cases in Denmark has been underestimated. So, factually there’s a lot of evidence to suggest that the absolute risk of COVID-19 hospitalization was lower in Denmark than in most other European countries. One of many factors I personally think that has contributed is the high adherence to the Covid guidelines from national health authorities.
• How did factors like age and comorbidities affect the absolute risk in RA patients?
  As an indirect testament to the validity of the analysis, the “usual” risk factors of severe COVID-19 were also relevant within the RA population in our study. So, patients of older age and male gender were at higher risk, as were patients with comorbidities, especially those with chronic lung disease and/or cancer.
• Regarding vaccination, what are the main learnings regarding COVID-19 -vaccination of RA patients?
  I think the main learning here is that even though patients with RA had an increased risk of being hospitalized with COVID-19 both before and after vaccination, the relative benefit of vaccination was similar to that of their peers; and that is extremely important because the vaccinations were generally and on a global level so effective in reducing the burden or daily impact of this disease. At least until the present day.
• How about patients that were unvaccinated and admitted to hospital – have they now been vaccinated and what do you consider the best way to follow-up on these patients?
  This is an interesting question! In our study, we looked exclusively at patients with RA, and the good news is that the there was a very high proportion of patients who received both a first and second vaccination, also among those that had been hospitalized due to COVID-19 before they had received their first vaccination shot. The proportion was higher than observed in the general population, and that is impressive because the general participation level in the COVID-19 vaccination program in Denmark was very high compared with other countries.
• How does having chronic inflammation contribute to the risks regarding contracting covid?
  From other infections in patients with RA, strong associations between higher disease activity and risk of infections have been shown, but in our data, we have not yet investigated this. Unfortunately it is not that easy to investigate: firstly, we know that the number of physical consultations, where signs of inflammation are registered, were lower during the pandemic. Secondly, when looking at the risk of contracting COVID-19, there would be numerous important confounders that we would not have information on in our patients, such as adherence to social distancing measures, a history of travel etc. In addition, these parameters would also be relevant for household contacts. On a personal note, I would expect the level of chronic inflammation to have a higher impact on the risk of having a serious outcome of a COVID-19 infection rather than on contracting the infection.
• Which measures can be taken to ensure that RA patients continue in their vaccination programme?
  This is an important aspect that I am certain clinicians are discussing. There was some compelling data coming out of Sweden, that compared the outcome of COVID-19 versus seasonal influenza in patients with RA and matched controls; and to me it stood out how much more serious COVID-19 was in terms of the rates of hospitalization. If this can be conveyed to patients in a sensible and serious way, then I think this would convince many patients that taking the relevant COVID-19 vaccines is worthwhile. Rheumatologists already talk to their patients about vaccinations for other conditions, and it may sound easy for me to just say “put it on the list”, but that is nonetheless where I think it should be and remain: on the list of important vaccinations for our patients with RA.
• Which changes are needed in care of RA patients to reduce the risks?
  I don’t see a need for any specific changes, but rather to stick to what we daily try to adhere to in the clinical work: treat to (a) target with the necessary medication and minimize the use of glucocorticoids.
• Have you looked at ‘late Covid’ in RA patients?
  This is an area that we haven’t really dived into yet, but we would like to investigate it in the future.
• What would be the most import thing for your colleagues to know re Covid-19 and RA?
  Put on the spot, I would say it is important to know and remember that most patients with RA had a really good effect of being vaccinated against COVID-19 when compared to their peers. That is something that seems to be valid across all countries and, so far, all COVID-19 strains.
• How do you see Covid affecting RA as a disease going forward?
  It is impossible for me to predict what SARS-CoV2 is going to mean to the world in the next years and decades, for instance if it is going to stay around and have a large impact on our lives or if it will fade to become “another seasonal flu”. Regardless, my guess is that whatever severity COVID-19 infections will have on non-RA individuals, RA patients will experience the same. Still, the overall risk of having a serious outcome will most likely remain increased in patients with RA.

René Cordtz is a medical doctor and a post-doc at The Center of Rheumatic Research Aalborg at Aalborg University Hospital in Denmark. He has worked in the field of rheumatic epidemiology for more than 10 years, and has investigated intensively into COVID-19 risks in rheumatic patients for the past 3 years.