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Since the beginning of the COVID-19 pandemic, researchers around the world have been working to determine the implications of the coronavirus on people living with rheumatic diseases, and particularly on those who take immunosuppressant medications.
“We’re still learning about whether our patients are at higher risk of getting COVID-19 and then having severe outcomes from COVID-19,” says Medha Barbhaiya, MD, a rheumatologist at Hospital for Special Surgery (HHS). “There’s also the question of whether there are differences among patients with certain rheumatic conditions, like lupus or rheumatoid arthritis.”
However, new data presented at the annual meeting of the American College of Rheumatology, ACR Convergence 2021, is shedding more light on how COVID-19 affects rheumatic disease patients — and experts are hoping the answers to these questions will better inform responses to future waves, variants, and infectious diseases as a whole.
Here is the latest research you should be aware of if you live with a rheumatic disease.
Check out this separate round-up on the latest information on the COVID-19 vaccine in rheumatic disease patients.
For more research breakthroughs from ACR 2021, check out our main guide: 100+ Arthritis & Rheumatic Disease Updates You Need to Know.
1. COVID-19 Infection in Rheumatic Patients
A growing body of research has found that rheumatic disease patients don’t always have a higher risk than the general population of contracting COVID-19. Factors that may increase risk include underlying comorbidities or certain medications.
In the largest systematic review to date on COVID-19 in rheumatic and musculoskeletal disease, researchers conducted a literature search across 14 databases. They included observational studies and experimental trials of rheumatic musculoskeletal disease (RMD) patients that tracked the comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/ICU admission/mechanical ventilation, and death. Of the 5,799 abstracts screened, 100 studies met criteria for inclusion. Of 46 studies that reported comparative rates of SARS-CoV-2 infection in people with RMD compared to people without RMD, 15 showed increased rates, 28 showed no difference, and four showed decreased rates.
Some of this may have to do with the individual measures that people take to protect themselves. Some people with conditions like rheumatoid arthritis or lupus may be more likely to avoid risky behaviors that increase their chances of contracting COVID-19.
“The reassuring thing is that rheumatic disease patients overall don’t seem to be doing worse than the general population in terms of contracting COVID-19, except for those with underlying comorbidities or underlying use of certain medications,” says Dr. Barbhaiya, who wasn’t involved in the study. “I think vaccination has played a huge role in protecting our patients as well.”
2. COVID-19 Complications in Rheumatic Patients
Although research is mixed, studies generally show that rheumatic patients may have a higher risk of hospitalization and other poor outcomes from COVID-19.
A large study presented at ACR Convergence 2021 investigated whether rheumatic patients are at higher risk of being hospitalized than the general population. Adult patients with inflammatory rheumatic diseases were asked to participate and register their own healthy control subject of the same sex and comparable age. From April 2020 to March 2021, 3,279 rheumatic patients and 1,110 healthy controls partook in the study.
Diagnosis of COVID-19 was confirmed in 307 (9 percent) of patients and 128 (12 percent) of healthy controls. However, the COVID-related hospitalization rate was significantly higher in patients compared to controls: 18 patients (6 percent) but just 1 healthy control (1 percent) were hospitalized.
Patients who were older, male, had a history of chronic pulmonary diseases or diabetes, or who were treated with prednisone or rituximab were more frequently hospitalized. On the other hand, patients treated with hydroxychloroquine or TNF inhibitor biologics were less frequently hospitalized.
Meanwhile, in a large systematic review and meta-analysis of 35 observational studies (including 68,537 patients with rheumatic disease), researchers found that patients with rheumatic diseases had a similar rate of COVID-related hospitalization as non-RD controls — but poorer in-hospital outcomes and higher mortality. In particular, conventional disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids were associated with increased risk for hospitalization. However, patients on biologic/targeted synthetic DMARDs had a decreased risk of hospitalization.
In another study, Canadian researchers looked at data from February 6, 2020 to April 15, 2021, matching people with a rheumatic disease with up to five individuals without rheumatoid disease for similar age, sex, month and year of COVID-19 diagnosis, and health authority (a governance model used to deliver public health care to Canadian residents).
There was a statistically significant increase in the adjusted risk of hospitalization due to COVID-19 for individuals with rheumatoid arthritis, ankylosing spondylitis, gout, and other systemic autoimmune rheumatic diseases (but not systemic lupus erythematosus). Only patients with rheumatoid arthritis and other systemic autoimmune rheumatic diseases (excluding systemic lupus erythematosus) had a significantly increased risk of ICU admissions. Individuals with rheumatic diseases did not have a significantly increased risk of mortality compared to the general population.
Another study of nearly 2,000 patients with systemic lupus erythematosus (SLE) presented at the ACR Convergence 2021 underscored the importance of controlling disease activity in those with lupus during the pandemic. In this study, more severe COVID-19 outcomes were seen in several groups of patients, including those with no SLE therapy, moderate and high disease activity, chronic renal disease, cardiovascular disease, and those on prednisone. These results reflect patterns seen in the general rheumatic disease population.
3. Impact of Medication on COVID-19 Outcomes
Patients on certain medications, like rituximab — a CD20 inhibitor — may be at higher risk of severe outcomes from COVID-19.
One study presented at ACR Convergence 2021 analyzed 114 cases of COVID-19 in CD20 inhibitor users and 559 matched comparators with COVID-19. Although risks of hospitalization and mechanical ventilation were similar between the two groups, people who were taking CD20 inhibitors, particularly long-term use, had higher mortality from COVID-19 than matched comparators.
In another study, researchers analyzed 16,342 patients positive with SARS-CoV-2. Of these patients, 1,477 were exposed to rituximab before their first positive COVID-19 test. Compared to the use of conventional DMARDs (which include methotrexate), baseline rituximab use was associated with double the risk of hospitalization.
Interestingly, anti-TNF biologics seem to be linked with a lower risk of poor COVID-19 outcomes compared with other immunosuppressive drugs. For example, in one study, researchers analyzed a total of 6,077 COVID-19 cases from 74 countries. Compared with TNFi monotherapy, there was a 70 percent higher risk of hospitalization or death observed in TNFi in combination with AZA/6-mercaptopurine, AZA/6MP monotherapy, methotrexate monotherapy, and JAKi monotherapy. “Among individuals with IMIDs [immune-mediated inflammatory diseases], TNFi monotherapy is associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory regimens,” note the researchers.
In another study, researchers analyzed data from 2,274 patients from a German physician-reported COVID-19 registry for rheumatic and musculoskeletal diseases between March 30, 2020 to April 9, 2021. The outcome of SARS-CoV-2 infection severity was defined in three groups: neither hospitalized, ventilated, nor deceased; hospitalized with or without non-invasive ventilation, but neither invasively ventilated nor deceased; and invasively ventilated or deceased.
Methotrexate monotherapy was used as reference for the analysis of the impact of rheumatic disease treatment. TNFi showed a significant association with a better outcome of COVID-19, while JAK inhibitors, immunosuppressants (mycophenolate, mofetil, azathioprine, cyclophosphamide, ciclosporin), and rituximab were independently associated with a worse outcome.
“These associations with a worse outcome of SARS-CoV-2 infection may be attributed to residual and unmeasured confounding due to higher burden of comorbidity or cumulative effect of therapies,” note the researchers.
4. Long COVID in Rheumatic Patients
Long COVID, the persistence of symptoms following COVID-19, is still poorly understood, but new research sheds light on its potential risk factors in rheumatic patients. There doesn’t appear to be major differences between the general population and those with rheumatic disease when it comes to the risk of long COVID, but certain medications, medical comorbidities, and smoker status may play a role.
“We need to determine if this is really going to be a long-term problem for our patients — and to what degree, to what extent, and how severe,” says Dr. Barbhaiya. “We really need to tease out what is long COVID and how it is different from their underlying conditions.”
In a preliminary study led by Dr. Barbhaiya and presented at the ACR Convergence, researchers surveyed adult patients who were evaluated at least once by a rheumatologist at a large rheumatology center in New York City. They collected data on sociodemographics, medical comorbidities, medication use, and health-related quality of life as well as detailed information about COVID-19 diagnoses.
Researchers compared “long-haul” COVID patients (those with symptoms persistent for at least one month) to those who had COVID-19 symptoms for less than a month. Among the 2,572 patients who completed the questionnaire, 254 patients noted a history of suspected or confirmed COVID-19 — and 55.9 percent of these patients had symptoms lasting longer than one month.
No significant differences in demographics, including age, gender, or race, were observed between the two groups. However, COVID-19 long-haulers were more likely to have one or more medical comorbidities and to be a current or former smoker.
While there was no significant difference in the percentage of long haulers with a systemic rheumatic disease (such as inflammatory arthritis, spondyloarthritis, vasculitis, lupus, etc.) compared to those without, patients with long-haul COVID-19 were more likely to have used corticosteroids for three or more months at the time of COVID-19 diagnosis. Further research is needed to establish whether chronic immunosuppression with corticosteroids predisposes patients to post-viral symptoms.
Read more here about the research on long COVID in rheumatic disease patients.
Effects of the COVID-19 Pandemic on Quality of Life
The effects of COVID-19 and its associated lockdowns have been far-ranging for those with rheumatic disease. Here’s what the latest research says about how the pandemic has affected aspects of patients’ quality of life.
5. Physical Activity
The pandemic has reduced physical activity in many patients with rheumatologic diseases — and for a variety of reasons.
In a new study presented at the American College of Rheumatology Convergence, researchers surveyed 1,133 adult patients with rheumatologic diseases through an academic health care system in North Carolina between July and September of 2020.
Over half of the participants (55.5 percent) reported engaging in less physical activity since the start of the pandemic. Factors associated with less reported physical activity included male sex, lower income during the COVID-19 pandemic, poorer self-reported health status, lupus (SLE) diagnosis, and chronic pain, depression, and hypertension. Most participants (67.2 percent) reported not meeting their exercise goals during the COVID-19 pandemic. The most common reported barriers to physical activity included:
- Increased overall fear and anxiety (33.5 percent)
- Lack of motivation (32.4 percent)
- Fear of contracting COVID-19 specifically (32.1 percent)
“Widespread barriers to physical activity were reported in our study and are likely to continue impacting individuals beyond the COVID-19 pandemic,” Teresa Dickson, the lead author of the study and Clinical Research Coordinator on the research team of Dr. Saira Sheikh at the University of North Carolina at Chapel Hill, Thurston Arthritis Research Center, told CreakyJoints. “Lack of motivation was a barrier prior to the pandemic, exacerbated by the pandemic, and will likely remain a barrier to physical activity beyond the pandemic unless it is addressed head-on with tailored interventions.”
Although many barriers to physical activity still exist, there is hope that the COVID-19 vaccines will play a role in reducing at least one of them. “We are optimistic that with widespread availability of the COVID-19 vaccine, the fear and anxiety of contracting the coronavirus infection will decrease,” said Dickson.
From the very start of the pandemic, the usual ways of receiving medical care were disrupted. There was a substantial increase in telemedicine care for patients with chronic conditions, including autoimmune rheumatic diseases. Overall, research shows that patients are satisfied with telemedicine — though preferences for telemedicine visits vary by the reason for the visit.
How will telemedicine continue to play a role in health care going forward? To answer that, it’s important to understand perceptions and preferences about telemedicine of patients with autoimmune rheumatic diseases. CreakyJoints and the Global Healthy Living Foundation (GHLF) conducted an online survey among patients from ArthritisPower and Vasculitis Patient Powered Research Network online patient registries, plus several other patient organizations in a new study presented at the ACR Convergence 2021.
Researchers evaluated attitudes about telemedicine using the validated telemedicine perception questionnaire between June 18, 2020 and August 10, 2020. Of 618 participants who reported having telemedicine available, 449 (72.7 percent) reported having a telemedicine visit and 303 (67.5 percent) reported at least one telemedicine video visit (the remainder had a phone-only visit).
One a scale of 0 to 10, the average visit satisfaction score for telemedicine visits was 7.3, with 25.8 percent being very satisfied (score of 9 or 10). Video visits and a higher telemedicine acceptability score were associated with higher satisfaction, though preference for a telemedicine visit differed significantly by reasons for the visit.
Patients who had experienced telemedicine were more likely to prefer telemedicine for routine visits than patients who hadn’t had a telemedicine visit yet (73.7 percent versus 44.3 percent).
They were also more likely to prefer telemedicine for:
- Reviewing test results (64.8 percent vs. 53.8 percent)
- When considering changing medications (40.5 percent versus 26.8 percent)
- When starting a new injectable medication (18.9 percent versus 12.7 percent)
“These results suggest that because such patients prefer telemedicine for certain types of visits, maximizing effective use of telemedicine should take into consideration specific clinical scenarios and patient preferences,” note the researchers.
7. Medication Interruptions
Early in the pandemic and in February of 2021, patients with autoimmune rheumatic diseases experienced frequent medication interruptions. These interruptions were associated with a higher risk of severe disease flares.
Another new study from CreakyJoints, GHLF, and a team of researchers from the University of Pennsylvania and University of Alabama at Birmingham presented at the ACR Convergence 2021 analyzed trends in medication interruptions.
A total of 2,396 patients completed a median of six surveys. The most common autoimmune rheumatic diseases were rheumatoid arthritis, vasculitis, and psoriatic arthritis. Medication interruptions decreased significantly from April 2020 (11.2 percent) to December 2020 (7.5 percent) but increased to 13.5 percent in February 2021.
Medication interruptions were more commonly found in those with higher anxiety: These interruptions occurred in 10.5 percent of patients with a higher anxiety score compared to 7.8 percent in those with a lower anxiety score. Medication interruptions were also associated with a significant increase in the risk of severe flare (11.7 percent versus 7.5 percent).
Read more here about the research on medication interruptions, anxiety, and disease flares.
8. Mental Health and COVID-19
Emerging research shows that pandemic-related stress is associated with worse health and disease activity, highlighting the importance of stress assessments in clinical settings (and effective stress management techniques for patients).
In a new study of over 3,000 participants, researchers examined the role of general and COVID-specific stress during the early stages of the pandemic on patient-reported outcomes and comorbidities in rheumatic disease patients. The researchers found that general stress during the pandemic in 2020 was associated with significantly higher odds of subsequent worsening of all patient-reported outcomes and an increase in the Rheumatic Disease Comorbidity Index (which measures comorbidity burden). COVID-specific stress was associated with significantly higher odds of subsequent worsening of activity scores, health assessment scores, and fatigue.
Another study assessed well-being during the pandemic in European patients with rheumatic and musculoskeletal diseases. An online survey gathered data from nearly 1,800 participants who were divided into two groups: those with “poor well-being” and those with “good well-being.” Those with poor well-being had higher disease activity than patients who did not experience poor well-being (51.4 percent versus 41.3 percent), a higher risk of anxiety (54.3 percent versus 41.7 percent), depression (57 percent versus 42.1 percent), and poorer self-perceived health (53 percent versus 41.8 percent).
A higher proportion of patients who were physically active presented good well-being than those who did not (54 percent versus 46.5 percent). More patients who did not walk outside (56.2 percent) or who didn’t have elements in their home to make outside contact possible (63.3 percent) experienced poor well-being.
The results show the importance of environmental factors and the role of patient organizations in addressing the effects of a pandemic during lockdown.
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Dickson T, et al. Perceived Impact of the COVID-19 Pandemic on Physical Activity Among Adult Patients with Rheumatologic Disease. Arthritis & Rheumatology. November 9, 2021. https://acrabstracts.org/abstract/perceived-impact-of-the-covid-19-pandemic-on-physical-activity-among-adult-patients-with-rheumatologic-disease.
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Interview with Alfred Kim, MD, Assistant Professor of Medicine, Pathology, and Immunology at Washington University
Interview with Dorry Segev, MD, PhD, a transplant surgeon and researcher at Johns Hopkins Medicine
Interview with Medha Barbhaiya, MD, a rheumatologist at the Hospital for Special Surgery (HHS)
Katz P, et al. The Association of General and Covid-19-Specific Stress with Changes in Patient-Reported Outcomes and Comorbidities. Arthritis & Rheumatology. Accessed November 7, 2021. https://acrabstracts.org/abstract/the-association-of-general-and-covid-19-specific-stress-with-changes-in-patient-reported-outcomes-and-comorbidities.
Patel N, et al. Association of CD20 Inhibitor Use with Severe COVID-19 Outcomes [abstract]. Arthritis & Rheumatology. Accessed November 22, 2021. https://acrabstracts.org/abstract/association-of-cd20-inhibitor-use-with-severe-covid-19-outcomes.
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Ugarte-Gil M, et al. Characteristics Associated with Poor COVID-19 Outcomes in People with Systemic Lupus Erythematosus (SLE): Data from the COVID-19 Global Rheumatology Alliance (GRA) [abstract]. Arthritis & Rheumatology. Accessed November 22, 2021. https://acrabstracts.org/abstract/covid-19-infection-and-outcomes-in-patients-with-rheumatic-diseases-a-systematic-review-and-meta-analysis.