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Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID‐19 Pandemic

Objective Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID‐19. We set out to understand how the COVID‐19 pandemic has impacted the lives of these patients in the United States. Methods Participants in a US‐wide longitudinal observational registry responded to a supplemental COVID‐19 questionnaire by e‐mail on March 25, 2020, about their symptoms, COVID‐19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free‐text comment fields. Results Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID‐19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID‐19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. Conclusion After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID‐19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.


INTRODUCTION
As the novel COVID-19 became a pandemic, there were early signs that people who were older, had a greater number of health conditions, or had immunodeficiencies would be at greater risk of contracting it and/or having more severe disease 1,2. Patients with rheumatic diseases are known to be at higher risk of infection because of immune dysregulation, comorbidities, and immune-modulating treatments 3-5. Many of these diseases (eg, rheumatoid arthritis [RA]) affect patients of an older age on average 6. Beyond the typical challenges of self-managing a chronic disease, disease management has become significantly more complex with the implementation of social distancing, including limiting nonessential health care visits. This has led to confusion about how patients with rheumatic diseases should balance managing their disease and reducing their risk of infection 7,8. In addition, there were early reports that treatments typically used for rheumatic diseases might be effective against COVID- 19 9. Most notably, in vitro studies and a small cohort study reported that hydroxychloroquine (HCQ) showed some benefits in treating COVID-19 10-12. HCQ is a commonly used conventional disease-modifying antirheumatic drug (DMARD) that reduces flares and mortality in systemic lupus erythematosus and is a common treatment for RA and other rheumatic diseases, In a small case-series, the interleukin-6 (IL-6) inhibitor tocilizumab, a biologic DMARD, also showed promise for treating respiratory manifestations related to COVID- 19 13. There are several ongoing clinical trials examining the use of tocilizumab or sarilumab as treatment for COVID- 19 14. These early reports and the emergency authorization by the Food and Drug Administration (FDA) of HCQ as a treatment for COVID- 19 have led to critical shortages in medication availability during a time when regular access to medication is inherently more difficult 15.
The objective of this study was to understand how patients with rheumatic and musculoskeletal diseases in the United States have been impacted by the COVID-19 pandemic through a onetime COVID-19 questionnaire querying their experiences during the last 2 weeks of March 2020.

PATIENTS AND METHODS
The study population consisted of participants in FORWARD, The National Databank for Rheumatic Diseases, a longitudinal open-enrollment observational patient registry 16. Participants are volunteers recruited primarily by US rheumatologists to complete comprehensive, semiannual questionnaires online, by mail, or by telephone interview. Participants included in this analysis responded to an online supplemental COVID-19 questionnaire focused on their experiences around COVID-19 symptoms, testing, and medication access in the 2 weeks prior to questionnaire completion. The supplemental COVID-19 questionnaire was sent via an e-mail link on March 25, 2020, to all FORWARD participants who had been invited to complete the current semiannual questionnaire. Responses to the supplemental questionnaire were collected between March 25 and April 1, 2020. In order to be included in this study, participants must have previously completed a semiannual questionnaire within the last 2 years. This study was approved by the Via Christi Hospitals Wichita, Inc., Institutional Review Board (IRB00001674), and all participants consented to participate.

Study variables. COVID-19 questionnaire.
Participants were asked about their rheumatic disease activity, development of any new symptoms (fever, cough, sore throat, shortness of breath, fatigue, muscle pain, headache, gastrointestinal symptoms, chest pain, abdominal pain, loss/change in taste or smell, and anxiety), testing for COVID-19, and any changes in their rheumatology treatment plan in the previous 2 weeks (See Appendix for full list of items). Participants were given the opportunity to share free-response comments about their experiences during the COVID-19 pandemic.
Semiannual questionnaire. The most recently completed semiannual questionnaire was linked to each participant's COVID-19 questionnaire. The following were assessed: demographics, including age, sex, race, education level, marital status, urban/rural area, history of smoking, body mass index, and health insurance status; primary rheumatic disease diagnosis; patient-reported outcome measures, including pain, global severity, fatigue, Health Assessment Questionnaire II (HAQ-II) score (a validated measure of physical function) 17, and Patient Activity Scale II [PAS-II] score (a validated measure of disease activity) 18,19; comorbid conditions, including heart disease, pulmonary disease, diabetes, renal disease, and liver disease; and medication use, including DMARDs, corticosteroids, and nonsteroidal anti-inflammatory drugs.
Screening criteria. Screening criteria were applied to supplemental COVID-19 questionnaire respondents based on March 20, 2020, CDC recommendations for SARS-CoV-2 testing priority 20 and included 1) fever, 2) at least one symptom of acute respiratory illness (new cough, dyspnea, sore throat, chest pain, or loss of taste/smell within the prior 2 weeks), and 3) at least one of the following: is 65 or more years old, is in a long-term care facility, has an autoimmune diagnosis, has a Rheumatic Disease Comorbidity Index (RDCI) 21 of at least 2, or is a health care worker/first responder.
Quantitative analysis. Differences between COVID-19 questionnaire respondents and nonrespondents were assessed with Student's t tests for continuous variables and χ 2 tests for categorical variables. Responses to all COVID-19 items were tabulated, and significance was assessed with χ 2 tests. All tests were two-tailed, and P values less than 0.05 were considered significant. Logistic regression modeled the association between disease activity and reported cancelation or postponement of appointments, with all sociodemographic information, RDCI, diagnosis, and number of rheumatology and general practitioner visits as covariables. Data were analyzed using Stata version 14.2 22.
Qualitative analysis. Two of the authors (YS and TAS) independently read and open coded the free-text comments using a grounded theory approach 23-25. They met to discuss their coding and notes and organized them into themes. Wordclouds.com was used to generate the word cloud, using the cloud graphic from Font Awesome version 5.13 as a template. The relative size of each word represents the frequency with which it appeared in the free-response comments.

RESULTS
A total of 7061 active FORWARD participants were sent the supplemental COVID-19 questionnaire. Of those, 530 participants responded during the first 7 days used for this report. RA was the most frequent diagnosis (61%). Geographic dis-| 337 tribution was diverse, with respondents representing 49 of 50 states (15% of respondents were from the Northeast, 31% were from the Midwest, 27% were from the South, and 25% were from the West). Compared with nonrespondents, respondents were more likely to be white, to have more education, to have completed their semiannual questionnaire online rather than on paper or by interview, and to have lower disease activity (Table 1).

Symptoms, screening criteria, and SARS-CoV-2 testing.
Approximately half of respondents reported experiencing new symptoms potentially associated with COVID-19 in the 2 weeks prior to questionnaire completion. The most frequently reported new symptoms were fatigue (18%), anxiety (16%), headache (13%), muscle pain (12%), and cough (10%) ( Table 2). Of the 530 respondents, 11 (2%) met COVID-19 screening criteria. Of those 11, two respondents had sought testing and, despite one of them reporting exposure to a confirmed case, neither received it. In addition, six others who did not meet the screening criteria reported an attempt to get tested for COVID-19, and three received testing. None tested positive for SARS-CoV-2 ( Figure 1).

Changes in rheumatology care.
Of the 530 COVID-19 questionnaire respondents, 471 answered questions about changes in their rheumatology care. Of these, 197 respondents (42%) reported some change to their care in the previous 2 weeks. Of the 197, 48% reported canceled or postponed appointments, 24% switched to teleconference appointments, 14% reported self-imposed changes to their medication list or dose, 11% reported physician-directed changes to their medication list or dose, 10% were unable to obtain their medication, and 4% were unable to reach their rheumatology office. Respondents with higher disease activity were more likely to report canceled or postponed appointments, even after controlling for demographics, comorbidities, and frequency of rheumatology/general practitioner appointments in the past (odds ratio 2.4 [95% confidence interval 1.3-4.6]; P < 0.01). Respondents who reported experiencing new symptoms associated with COVID-19 in the last 2 weeks were more likely to have had medications added or removed by their physician (Table 3).
Patient experiences. The qualitative analysis identified the following four major themes from 211 respondents' free-response comments: emotions in response to COVID-19-related experiences, perceptions of risk, protective measures to reduce risk of COVID-19 infection, and impacts on rheumatic disease treatment and access to care, including medications and rheumatology consultations (Table 4 and Figure 2).
Emotions in response to COVID-19-related experiences. The most commonly reported emotions were anxiety, nervousness, worry, and fear. Respondents worried about being infected and developing COVID-19, whether they would survive an infection, how their medications would affect their risk, and the impact of the pandemic on access to medications and health care. Some noted that the anxiety/stress seemed to worsen their arthritis symptoms. In response to the threat of COVID-19, most respondents reported a desire to reduce their risk and take actions to protect themselves. Only a small minority of participants expressed a lack of worry toward COVID-19. Participants were asked if they had experienced any new symptoms in the 2 weeks prior to questionnaire completion; they selected from a provided list of symptoms related to COVID-19.  Respondents also reported feeling uncertain about whether to stop taking their medications as well as whether their symptoms were due to COVID-19 or another condition, such as allergies. They felt frustrated when confronted with difficulties in accessing medication or obtaining permission to work from home. Practicing social distancing caused feelings of sadness and loneliness in respondents who could no longer see family and friends in person.
A few commenters expressed positive emotions such as feeling grateful (eg, for the support of family or colleagues), hopeful, or wanting to help. One person did not want to get tested for COVID-19 despite having symptoms consistent with COVID-19 because they had quarantined at home since getting sick and did not want to waste scarce testing supplies. Some acknowledged the need to manage negative emotions and stress.
Perceptions of risk. Many participants expressed beliefs about their increased risk of infection/severe outcomes due to COVID-19 related to older age, chronic conditions, or exposure through the workplace or contact with family members. Many thought that use of immunosuppressive medications increased their risk/potential severity of COVID-19 and that stopping such medications could reduce their risk. This belief seemed to stem from previous experiences of being instructed to stop immunosuppressive medications during infections or before surgeries. A minority thought that taking HCQ might lower their risk of developing COVID-19. Some commenters described setting personal limits for acceptable/unacceptable risk, such as planning to stop going to work once COVID-19 cases emerged at their workplace.
Protective measures to reduce risk. The majority of respondents described adoption of self-isolation and social distancing measures, often in response to state shelter-in-place orders. They reported actions such as stopping in-person contact with family and friends, staying at home except to buy groceries and go to medical appointments, having groceries and meals delivered, canceling all but the most critical medical appoint-ments, and canceling travel plans. Some participants were able to arrange working from home, but others (mostly health care workers) could not. Several also discussed wearing masks or using gloves when they needed to go to a grocery store or pharmacy, but that other shoppers did not always respect the recommended distance of 6 feet. Adapting physical activity routines to adhere to social distancing could be challenging because some participants were accustomed to exercising in an indoor public space or with friends. Walking or running outside, sometimes with a pet, was reported as a common alternative activity.
Impacts on treatment and access to care. As discussed above, some participants reported stopping their DMARD use to lessen their risk of infection, sometimes with the approval of their rheumatologist. Others continued to take their medications as usual. Many reported having medical appointments canceled or switched to telephone or video consultations. Infusions were still received as scheduled by most respondents. Availability of medications, particularly HCQ, was a frequent concern, and some people reported being unable to obtain refills from their pharmacy. Some attributed the shortage of HCQ to widespread misinformation that this medication was proven to be an effective treatment for COVID-19. One person reported concern over losing health care coverage (and as a result, access to rheumatology care) because of the economic impact of COVID-19.

DISCUSSION
In this study, we report how patients with rheumatic and musculoskeletal diseases throughout the United States were impacted by the COVID-19 pandemic during the latter half of March 2020, the relatively early days of government-imposed isolation decrees.
Although none of the respondents tested positive for COVID-19, many were already affected by it. One-fifth of respondents reported postponed or canceled medical appointments, and half reported new symptoms associated with COVID-19. Our qualitative Disease activity was defined by Patient Activity Scale II (PAS-II), with a PAS-II score of 3.7 or less as low disease activity and a PAS-II score of more than 3.7 as high disease activity 27. Many respondents were not sure if they should stop their medications-additional evidence-based guidance is needed in this area for patients and rheumatologists. Recent editorials are recommending not modifying treatment unless symptoms of COVID-19 manifest 7,28. It is important for clinicians to be aware that some patients have stopped taking their medications without a recommendation from a health professional.
Respondents with higher disease activity were more likely to have canceled/postponed appointments even after adjustment for several important confounders such as comorbidities and frequency of clinical appointments; it is unclear if this decision was made by the participant or physician because less controlled disease often comes with greater infection risk. Further study is needed to understand how lack of appointments for those likely more in need of health care follow-up may impact patients' health. Similarly, patients reporting new symptoms were less likely to have been able to reach their rheumatology clinic and were more likely to have had their physician change their medications; new symptoms likely led patients to contact their physicians, leading to these findings.
Initial reports suggesting HCQ as an effective COVID-19 treatment 11,29 have come under increased scrutiny because of questionable methodologies and conclusions 30,31. The unconfirmed reports of HCQ as a viable treatment option for COVID-19, along with FDA emergency authorization for use in cases of hospitalization and the resulting shortage/refusal by pharmacies to refill prescriptions, is a major issue for patients and the rheumatology community 32,33. Although additional studies launch to examine this in greater detail, there is a need to raise awareness that HCQ is not yet a proven treatment or prophylactic for COVID-19 and is a critical medication for many patients with rheumatic diseases and reduces mortality and flares in patients with lupus 34. As one participant wrote, "I have taken Plaquenil for over 20 years and cannot get any now as it's being used as a possible treatment for Covid19.
[…] I feel close to hopeless." Our study has some important limitations. With a single e-mail as the basis of our initial questionnaire, there was possible bias toward participants with greater socioeconomic status, fewer symptoms, and lower disease activity. We accounted for this difference by comparing respondents with nonrespondents who had completed their semiannual questionnaire. Future work should also examine the impact on more vulnerable populations, ie, those with lower socioeconomic status or lower education and/or those from racial/ethnic minorities. It is also likely that study participants who were diagnosed with COVID-19 or hospitalized were not able to respond during this short time period. It is important to note that because this cohort is composed entirely of patients with rheumatic diseases, our ability to differentiate between results that are specific to the rheumatology community and those that are likely to be the case throughout the population is limited. Lastly, comments were not required of participants, and our qualitative analysis was inherently biased toward those who found the need to add additional detail on their experiences beyond our questionnaire.
In summary, we found that after 2 weeks, many participants in the United States with rheumatic diseases already had important changes to their health care, including canceling appointments, which was independently linked to increased disease activity, and

Theme
Example Quote Unavailability of medications (especially hydroxychloroquine) "I tried to get one extra refill on my hydroxychloroquine, after Trump lied about it being useful for cv-19, because I could see that would cause a run on the drug. I was denied the refill by my pharmacy provider, [pharmacy name], because it was not yet due for refill. After reading that the AHIP was urging companies to allow an extra refill for necessary maintenance medications, I wrote an enote to [pharmacy name] asking them to reconsider their denial and send me the medication now so that I have it to assure continuity of my treatment plan in the future. I have yet to hear back from them." Loss of health care coverage "I may lose health care coverage within the next 30 days due to economic changes during this crisis. This may severely affect my rheumatology care." Abbreviation: DMARD, disease-modifying antirheumatic drug. Table 4. (Cont'd) Figure 2. Word cloud demonstrating the top themes and most frequently seen words in respondents' free-response comments.
altering medications without professional consultation or because of hydroxychloroquine shortage. There were important impacts on mental health and continued uncertainty on how best to treat these diseases and stay protected from COVID-19. Participants who met priority screening criteria for SARS-CoV-2 testing were not tested, those who were tested did not meet screening criteria, and none tested positive. We have planned follow-up questionnaires with similar questions and the ability to modify them as guidelines change and as participants report testing positive for COVID-19. As evidence accumulates on the effectiveness of potential COVID-19 treatments, many of which are used in treating rheumatic diseases, effort is needed to ensure continued access to treatments that have already been proven effective for rheumatic diseases.

ACKNOWLEDGMENTS
We are grateful for the additional contributions by Rebecca Schumacher and Dr. Jacob Clarke in the creation and implementation of the supplemental survey. None of this work could be done without the contributions of our participants. In addition, we thank several of our partners who took extra time with home childcare so that we could finish this study in a timely manner.