Are autoimmune rheumatic patients more susceptible to COVID infection?
Autoimmune patients are considered at high risk for infections due to their abnormal immune system and due to the immunomodulatory treatments used. Evidence suggests that patients with rheumatic disease have a slightly higher risk of infection with SARS-CoV-2 compared with the general population relative risk of 1.52 (95 % CI 1.16–2.00). Patients with rheumatoid arthritis (RA) have 25% to 60% higher risk of contracting infection.
Overall infection fatality rates range from 0.5% to 2.7% in this group. Poor outcomes are overall influenced by the presence of comorbidities (age >65 yrs, DM, CKD), high disease activity and use of certain DMARDs and steroids.
Is the COVID burden in rheumatology getting better?
Over the past two years since the pandemic started in 2020 until the Omicron wave in 2022, it appears that worst outcomes have lessened for those with systemic autoimmune rheumatic disease (as well as for the general population). Severe COVID cases in rheumatic disease rate dropped from 46% in June 2020 to 15% in January 2022. Death rates in rheumatic diseases also dropped from 8.8% to 2% during the same periods.
Do rheumatoid arthritis medications affect your ability to fight COVID-19?
Certain immunosuppressive medications may impair the ability of the immune system to fight the coronavirus by lowering levels of T cells and B cells. After analyzing data for more than 2,800 people with rheumatoid arthritis in the COVID-19 Global Rheumatology Alliance Physician Registry, researchers found that people with rheumatoid arthritis who were taking rituximab (Rituxan) or JAK inhibitors were more likely to have severe COVID illness requiring hospitalization than patients on other DMARDS.
Other studies have shown that prednisone and methotrexate may also adversely affect your response to COVID-19 infection.
That said, a poorly controlled autoimmune disease is much more of a threat to someone with COVID-19 than these medications.
Which vaccine should patients get and how many booster doses?
Pfizer and Moderna mRNA vaccines are preferable in autoimmune disease patients. Patients with immunocompromised status likely do not produce sufficient antibody response with primary series and need a third dose of the COVID vaccine. On March 29, 2022, the CDC updated their recommendation to include a booster dose or fourth dose for immunocompromised persons using the Pfizer or Moderna vaccine.
Do immunosuppressive medications reduce the COVID-19 vaccine response?
There is some evidence suggesting that medications used for autoimmune arthritis may reduce the vaccine response:
- About 10-fold reduction of vaccine response in patients who used high-dose corticosteroids (>20 mg of prednisone) regularly
- About 36-fold reduction of vaccine response in patients who use B-cell inhibitors, like rituximab
- Mild reductions in patients using TNF inhibitors, methotrexate and sulfasalazine, JAK inhibitors and IL-12/23 inhibitors
To maximize protection, these patients on B-cell inhibitors and some T-cell mediated medications may need additional measures, like the pre-exposure drug cilgavimab/tixagevimab (Evusheld) to boost protection.
Do patients have to hold off their autoimmune medications before or after the COVID vaccine?
As per ACR guidelines, if underlying disease activity permits, certain immunosuppressive medications are to be held for proper COVID vaccine response.
- Methotrexate, oral calcineurin inhibitors, JAK inhibitors, mycophenolate, abatacept (Orencia) injectable form, cyclophosphamide infusion: Skip for one week after each vaccine dose.
- Abatacept (Orencia), IV form: Get the COVID-19 vaccine four weeks after your last infusion, then skip a week and get next infusion.
- Rituximab (Rituxan): Get the COVID-19 vaccine approximately four weeks before next infusion, then delay next infusion by two to four weeks after second vaccine dose.
Other commonly used autoimmune medications don’t need to be held for vaccination.
Are vaccines/boosters recommended for people who have already had the infection?
We still don’t know how long immunity lasts from natural infection, but research shows that vaccine immunity tends to be stronger than natural immunity, so vaccination is strongly suggested for people who have had COVID-19. Some experts advise waiting about 90 days from the time of the COVID-19 diagnosis to get vaccinated. For these people, the combination of vaccination and infection results in “hybrid immunity,” which produces a long-term protective response similar to an additional booster dose.
Who qualifies for monoclonal antibodies in COVID-19?
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off viruses. They are indicated for immunocompromised patients who have spent at least 15 minutes or longer within six feet of someone who has tested positive, and these antibodies are most effective in the earlier stages of disease. They may not provide much help to patients already hospitalized with severe disease.
How do you treat COVID in autoimmune patients?
General management of patients with COVID-19 who are immunocompromised should be individualized based upon their underlying disease activity, the specific immunosuppressants being used and severity of COVID-19.
Are immunosuppressed patients susceptible to breakthrough infections?
Vaccine effectiveness for prevention of symptomatic COVID-19 in those on immunosuppression was 71% compared with 94% in immunocompetent individuals. Similarly, vaccine effectiveness for avoiding hospitalization was lower in immunosuppressed than in immunocompetent individuals (62.9% versus 91.3%). Data from the EULAR COVID-19 registry and COVAX registry suggest that breakthrough rates are low (<1%) in fully vaccinated individuals with inflammatory diseases.
Post COVID/Long COVID: A new pandemic
A recent study in the United Kingdom showed 41% of people affected by COVID had symptoms of long COVID for more than a year, and 19% for more than two years. Rates of long COVID are lower in people who are triple vaccinated, 5% for the Delta variant and 4.2% for Omicron BA.2.
Is this long COVID or a rheumatic flare?
Long COVID symptoms include breathlessness, cough, fatigue, arthralgia, sleep disturbance and myalgia. Fibromyalgia and systemic autoimmune rheumatic diseases like RA and SLE share similar symptoms with long COVID, which poses a significant challenge to clinicians.
What causes long COVID?
The actual cause of long COVID is not fully known, but four speculated pathogenesis theories have been proposed.
- A chronic, low-grade inflammatory response, especially in patients who were hospitalized
- Multi-organ microvascular disease with thrombosis and endothelial dysfunction
- Autoimmune response, where the body starts to recognize its own tissues and organs as foreign
- COVID-induced neurological damage, particularly to the autonomic nervous system
Social issues like financial strain, job loss and social isolation, poor mental health and inability to access services also contribute to long COVID.
Does post-COVID have an autoimmune base?
Systemic autoimmune-related manifestations in COVID-19 are likely from a hyperinflammatory reaction triggered by the virus that results in tissue damage. Dysregulated production of autoantibodies targeting GPCRs and RAS-related molecules in COVID-19 patients was higher in patients with classic autoimmune diseases when compared to healthy controls. Some reports found that the levels of rheumatoid factor (RF) and double-stranded DNA (anti-dsDNA) were significantly increased according to COVID-19 severity.
References
Grainger, R., Kim, A.H.J., Conway, R. et al. COVID-19 in people with rheumatic diseases: risks, outcomes, treatment considerations. Nat Rev Rheumatol 18, 191–204 (2022).
Curtis, J.R., Johnson, S.R., Anthony, D.D., Arasaratnam, R.J., Baden, L.R., Bass, A.R., Calabrese, C., Gravallese, E.M., Harpaz, R., Kroger, A., Sadun, R.E., Turner, A.S., Williams, E.A. and Mikuls, T.R. (2022), American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 4. Arthritis Rheumatol, 74: e21-e36.
Rojas, M., Rodríguez, Y., Acosta-Ampudia, Y.et al. Autoimmunity is a hallmark of post-COVID syndrome. J Transl Med 20, 129 (2022). https://doi.org/10.1186/s12967-022-03328-4
Dr. Madhavi Siddhanthi
Dr. Siddhanthi received her bachelor’s degree and medical degree from Guntur Medical College in Guntur, India. She completed her internship and residency at the University of California, Los Angeles Kern Medical Center, where she was chief resident. Dr. Siddhanthi completed a fellowship in rheumatology at Cedars-Sinai Medical Center. Board-certified in internal medicine, she is a member of the American Medical Association, American College of Rheumatology and American College of Physicians. She has been with Wellstar since 2012.
