COVID-19 Vaccination in Autoimmune Diseases: Patient Perspectives and Concerns

covid19 vaccine, vaccination
Digital generated image of huge COVID-19 vaccine bottle standing surrounded by people against white background.
In this interview, Laurent Arnaud, MD, PhD, and Laura Boekel, MD, each discuss findings from their studies on the perspectives and concerns of patients with autoimmune diseases regarding COVID-19 vaccination.

This feature is part of the Autoimmune Disease Awareness Month series.

The Centers for Disease Control and Prevention (CDC) recommends that individuals with autoimmune diseases and those with weakened immune systems receive the COVID-19 vaccines; however, no solid data are currently available regarding their safety specifically in populations with autoimmune conditions.1 On the other hand, researchers have indicated that patients with autoimmune and inflammatory conditions vs the general population may be at increased risk for COVID-19-associated hospitalizations and worse disease outcomes, suggesting that the benefits of vaccination outweigh the risks.2 In February 2021, the American College of Rheumatology (ACR) also released detailed clinical guidance for providers regarding COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases.3

However, as part of 2 separate survey findings published in Lancet Rheumatology, patients with autoimmune diseases expressed their perspectives, concerns, and hesitancy towards COVID-19 vaccination due to several factors, including the rapid rate of development and approval of the vaccines, low knowledge of vaccines and associated technologies, and fear of disease flares and reactions or side effects.4,5

In addition, with the recent news on the “outdated” and “misleading” information surrounding the AstraZeneca COVID-19 vaccine, there is predicted to be an increased public mistrust towards the overall scientific process.6 How can health care providers help change the mindsets of the already/potentially vaccine-hesitant individuals and the community at large?

We spoke with an author on the Vaccinations Against COVID-19 (VAXICOV) study paper, Laurent Arnaud, MD, PhD, a professor of rheumatology at the Department of Rheumatology at the University Hospitals of Strasbourg and the French National Reference Center for Rare Autoimmune Diseases. We also interviewed the lead author of the paper on the perspectives of patients with autoimmune diseases on COVID-19 vaccination, Linda Boekel, MD, of the Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.

Findings from the VAXICOV study showed that approximately 35% and 15% of patients with systemic autoimmune or inflammatory rheumatic disease reported uncertainty and unwillingness, respectively, toward getting vaccinated against SARS-CoV-2. Dr Arnaud, what were some of the main concerns of these patients?

Laurent Arnaud, MD: The reason why we conducted the VAXICOV survey was to get an idea about the percentage of patients and health care professionals who would be concerned about COVID-19 vaccination, and also to understand their concerns as a way to address them. This was central to the design of the study.

If I have to [highlight] the main concern, I would say that it is mostly a lack of trust. We have had several questions to analyze [these concerns] in more detail, and it pertained to 3 things. First, the fact that these COVID-19 vaccines are new, that they have been developed in a short period of time, and the fact that they have included new vaccine technologies, especially the messenger RNA (mRNA) vaccines. The second concern was about the side effects; the fact that maybe the vaccines could induce a flare of the rheumatic disease or another type of disease, such a chronic infection or cancer, or something that came back quite often. The third element was some kind of lack of trust — concerns about the management of the health crisis by governments and the financial relationships between governments and pharmaceutical companies.

With VAXICOV being an international study, was there a similarity in concerns about COVID-19 vaccination among populations in different parts of the world?

Dr Arnaud: These results are not shown in the paper,4 but especially regarding the proportion of refusal or potential refusal [of the vaccines], there were some huge variations between countries. For instance, France had a high rate of refusal or expected refusal, but it was more moderate in the United States. I think we already know that, [with respect to the vaccines], there were some differences in the behavior [of individuals] between the countries, but now, this is also confirmed for their attitude towards [COVID-19] vaccination.

Both the editorial comments published in Lancet Rheumatology4,5 have emphasized the integral role of the rheumatologist in COVID-19 vaccination uptake. Findings from the analyses have indicated that the willingness of patients with autoimmune diseases to receive the COVID-19 vaccines depended on advice from their specialists. Could you each provide information on how rheumatologists and rheumatology providers can guide patients in making informed decisions and improve their willingness towards COVID-19 vaccination?

Dr Arnaud: [It was found in the VAXICOV study] that the willingness of patients with autoimmune or rheumatic diseases to get the vaccines highly depended on recommendations from their rheumatologist.4 I think this is because of the fact that, in many cases, these patients receive immunosuppressive agents or biologics, which is a source of concern. [Patients] know that these medications increase the risk for severe COVID-19; this is especially true for those who receive rituximab. Because there is an increased risk for severe COVID-19, I think the rheumatologist knows how to manage [such] situations; they also know whether the vaccines can be indicated or not, given the risk level in these patients.

But how can the rheumatologist contribute to the dissemination of this information? There are some guidelines and recommendations for COVID-19 vaccination by the ACR3 and the [European League Against Rheumatism] (EULAR).7 Being the president of the European Lupus Society, we have also made some specific recommendations for patients with lupus. So, I really think that rheumatologists are very much involved in the building of knowledge and its dissemination.

Dr Boekel: Data [from our study]5 show that the important reasons for vaccine hesitancy are a lack of long-term research and concerns for adverse events and exacerbations of the underlying autoimmune disease. Addressing these concerns during patient contact, while simultaneously explaining the benefits of COVID-19 vaccination, can therefore improve vaccination willingness of patients with autoimmune diseases.

As a follow-up to that, Dr Boekel, what are the legitimacy of the major patient concerns reported in the study (risk for adverse events and lack of long-term research)5 and how can they be addressed with patients?

Dr Boekel: Results of previous studies on vaccines against other viruses are reassuring; few adverse events and diseases flares in patients with autoimmune diseases have been described.8 To what extent these results are applicable to COVID-19 vaccines and how efficacy rates of COVID-19 vaccines in patients with autoimmune diseases compare to efficacy rates in the general population are still unknown. However, especially because the infection rate of COVID-19 is currently high, the benefits of vaccination against COVID-19 outweigh the possible risks.

Our data show that a rheumatologist’s advice to get vaccinated against COVID-19 leads to a (positive) change in vaccination willingness in 69% of patients who were indicated as hesitant towards COVID-19 vaccination and 31% of patients who were indicated as refusing COVID-19 vaccination.5 Based on our results, this means it is beneficial in 1 in 5 patients to address the subject of COVID-19 vaccination during patient contact. Explaining the benefits of COVID-19 vaccinations and reassuring patients with results of data on other vaccines may aid in reducing patients’ concerns and increasing their vaccination willingness.

During the pandemic, there has been an information overload as well as the rapid spread of misinformation about the COVID-19 vaccines among all populations, but especially among patients with autoimmune diseases. What is the role of providers in mitigating the spread of false information?

Dr Arnaud: There are different ways to do that. Many patients have access to social media. From a health care perspective, there have been a lot of virtual meetings; unfortunately, we cannot do physical meetings to discuss and disseminate the information. I also believe quite a lot in direct mailing from health authorities and within the health care networks for dated information. We are receiving, several times per day, emails from the French government, [specifically] the health ministry, about updated information regarding new variants and the efficacy of vaccines, and I think this is really important.

Dr Boekel: Data that we did not publish, but have collected, determined the extent to which people kept up-to-date with the developments of the COVID-19 pandemic and the sources of information that they used. These data demonstrated that nearly 70% of both patients and healthy control participants followed COVID-19 news on a daily basis, and that news shows (85% and 87%, respectively), journals (63% and 70%, respectively) and press conferences (57% and 62%, respectively) were the most important sources of information. Talk shows and social media were used considerably less as a source of information (38% and 15%, respectively, of the entire cohort).* This indicates that the way in which COVID-19 vaccines are discussed in news items may influence the vast majority of the population, including patients with autoimmune diseases.

Dr Arnaud, an important finding of the VAXICOV study was the low vaccine hesitancy among health care providers. It was noted that the reason that they wanted to get vaccinated against SARS-CoV-2 was to protect the general population. Could you discuss some of the concerns of health care providers about COVID-19 vaccination?

Dr Arnaud: Hopefully, only a very small minority of health professionals were reluctant, less than 10%,4 which I think is quite low but maybe too much. Their concerns, in some way, were the same as that of the patients, especially regarding the fact that these are new vaccines that have implemented new technologies and have been developed in a short period of time. The difference with the patient population was that they feared flare of the disease induced by the vaccine, and that was not [a concern for] the health professionals.

What clinical implications do each of these studies4,5 have on the future of COVID-19 vaccination in patients with autoimmune diseases?

Dr Arnaud: We have conducted an analysis of the VAXICOV study, which has not been published yet. [We saw that] the main difference between the patients who agreed to be vaccinated vs those who were hesitant or refused to get vaccinated was not the fear of COVID-19, a severe case of the disease, or the [degree] of immunosuppression, which was quite similar between the study groups, but it was the fear of the side effects.*

What this could mean is there is a lack of understanding of the mechanism and the fact that this involves a new [vaccine] technology. So, I really think that the appropriate way for rheumatologists to increase vaccine uptake is not really to talk [with their patients] about the risk for severe COVID-19, which was the same across the study groups, but to be very reassuring about these new technologies: the fact that they are actually not so new and that we already have data with other vaccines, the fact that we are going to follow up with these patients very carefully, and that we are going avoid vaccinating them during their flares.

Dr Boekel: Our results provide guidance for rheumatologists in the issues that are relevant to address when their patients are hesitant towards COVID-19 vaccination (primarily the lack of long term research and fear of adverse events or exacerbations of the underlying autoimmune disease following COVID-19 vaccination). In addition, by demonstrating that encouragements to get vaccinated positively influences vaccination willingness in a considerable proportion of the entire patient population (>20%),5 rheumatologists may feel more motivated to address the subject of COVID-19 vaccination during patient contact. Our data may therefore contribute to increasing vaccination willingness of patients with autoimmune diseases, and therefore, consequently contribute to reducing COVID-19 related morbidity and mortality in these patients. 

*Editor’s Note: Dr Boekel and Dr Arnaud provided currently unpublished data to substantiate their responses. We will update the information and references when they become available.

Disclosures: Dr Laurent Arnaud declared affiliations with AstraZeneca, Pfizer, and Johnson & Johnson, and has received funding for research unrelated to the VAXICOV study. Dr Laura Boekel declared no affiliations.


  1. Centers for Disease Control and Prevention (CDC). Vaccine considerations for people with underlying medical conditions. Updated March 12, 2021. Accessed March 22, 2021.
  2. American College of Rheumatology. ACR COVID-19 vaccine guidance recommends vaccination, addresses immunosuppressant drugs & patient concerns. Press release. Published February 11, 2021. Accessed March 22, 2021.
  3. American College of Rheumatology. COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal disease. Updated March 4, 2021. Accessed March 22, 2021.
  4. Felten R, Dubois M, Ugarte-Gil MF, et al. Vaccination against COVID-19: Expectations and concerns of patients with autoimmune and rheumatic diseases. Lancet Rheumatol. Published online February 22, 2021. doi:10.1016/S2665-9913(21)00039-4
  5. Boekel L, Hooijberg F, van Kempen ZLE, et al. Perspective of patients with autoimmune diseases on COVID-19 vaccination. Lancet Rheumatol. Published online February 22, 2021. doi:10.1016/S2665-9913(21)00037-0
  6. AstraZeneca accused of cherry-picking vaccine study data. Associated Press. Published March 23, 2021. Accessed March 24, 2021.
  7. EULAR. EULAR view-points on SARS-CoV-2 vaccination in patients with RMDs. Updated December 2020. Accessed March 23, 2021.
  8. Westra J, Rondaan C, van Assen S, Bijl M. Vaccination of patients with autoimmune inflammatory rheumatic diseases. Nat Rev Rheumatol. 2015;11:135-145. doi:10.1038/nrrheum.2014.206