How did COVID-19 affect people with rheumatic disease?
Many of the concerns related to COVID-19 and rheumatic disease have been successfully addressed during the pandemic, and we know much more today than we did when first hit by the virus in early 2020.
A comprehensive article was recently published in Nature Reviews Rheumatology, describing what we have learned so far (1). This blogpost will give you a summary.
The risk of infection is slightly increased in people with rheumatic disease
When infected by a virus, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–the virus which causes covid-19–our immune system is activated with an aim to eliminate the intruder. This is accomplished by the combined actions of immune cells and antibodies neutralizing the virus.
People with autoimmune disease, such as rheumatoid arthritis (RA), systemic lupus erythematosus, psoriatic arthritis or ankylosing spondylitis, have an overactive immune system which attacks and damages the body’s own tissues. Treatment of these conditions aims to dampen the immune system, but when your immune system is suppressed, it doesn’t work properly and you become vulnerable to infections.
Several studies also show that people with RA are more susceptible to SARS-CoV-2 infection than the general population. Analysis of half a million people in the UK could show that the risk of infection was 34% higher for people with RA (2), and in a big study from the US, the risk was found to be 25% higher (3). Similar data also come from China, Spain and South Korea.
Still, other studies show no increased risk, and according to a so-called meta-analysis, where 23 independent studies were examined together, people with RA were only 1.5 times more likely to be infected than people without RA (4). Taken together, data today points towards a small increased risk of infection when you have a rheumatic condition.
COVID-19 outcomes – from asymptomatic to fatal
Most SARS-CoV-2 infected people are asymptomatic or have mild symptoms, like headache, fever, fatigue and sore throat. However, some develop severe COVID-19 that can be fatal. Our immune system plays a critical role in determining the outcome.
As with the higher infection rate, many studies also suggest that people with RA have an increased risk of severe COVID-19. This could for example be seen in a Danish study of 11,122 SARS-CoV-2 infected individuals (5). An important finding in this study though, was that when consideration was taken to age, sex and other medical conditions, people with RA no longer had an increased risk of severe COVID-19.
The Danish study highlights that other factors than those related to the rheumatic disease itself determines the outcome of COVID-19. For example, some rheumatic conditions are linked to lung disease, and having a lung disease increases the risk of severe COVID-19. A large international study, including >20,000 people with rheumatic disease and COVID-19, found that a poor COVID-19 outcome was primarily associated with old age and having another medical condition (6).
Is COVID-19 affected by anti-rheumatic treatment, and should you do anything about it?
The same study also found that use of corticosteroids, and treatment with the anti-rheumatic drug Rituximab, and possibly also the so-called JAK inhibitors, were risk factors for severe COVID-19. These drugs can be very effective in treating some rheumatic conditions by dampening an overactive immune system, but at the same time your ability to fight the virus is impaired.
As for the other anti-rheumatic drugs, no increased risk for severe COVID-19 has been found. The so-called TNF inhibitors may even be beneficial, and have been suggested as a future treatment for COVID-19 (7). Interestingly, other anti-rheumatic drugs, including the previously mentioned JAK inhibitors and corticosteroids, are already being used to treat severe COVID-19.
In some situations, stopping immunosuppressive treatment may be recommended if you are infected by SARS-Cov-2. The American College of Rheumatology, an organization for physicians, health professionals and scientists working in rheumatology, and the European equivalent, the European Alliance of Associations for Rheumatology, provides continuously updated guidelines and recommendations on COVID-19 and anti-rheumatic treatment for people with rheumatic conditions (8, 9).
Stopping anti-rheumatic treatment can lead to disease flares, and should never be done without consulting your doctor. Prolonged holding of medication should also not be necessary, as it has been shown that 100% of SARS-CoV-2 infected people with a normal immune system produces antibodies to the virus within 19 days of infection (10).
What about vaccines?
The incredibly rapid development and distribution of the COVID-19 vaccines has to be considered one of the greatest scientific and medical achievements in modern time (11). The vaccines are very effective, they trigger the production of antibodies against the virus in nearly all vaccinated people, and they protect against severe COVID-19 (12, 13).
Even though most people with rheumatic disease produce protecting antibodies, their antibody levels are lower (4, 14, 15). This phenomenon is mainly caused by the immune-dampening anti-rheumatic drugs. In particular treatment with Rituximab, a drug which reduces the number of antibody-producing cells (16).
If you’re taking immunosuppressive medication, vaccine booster shots can help work up those important anti-virus antibody levels (17), and if you are treated with Rituximab and your rheumatologist thinks delaying treatment is safe, then this could also be considered when taking the vaccine (8, 9).
Finally, should you worry about disease flares when taking the vaccine? The short answer is no, there is no need to worry. Reassuring data comes from four big studies, together including over 6,000 people with rheumatic disease, where no flares could be identified as caused by the COVID-19 vaccination (14, 15, 18, 19).
We have to keep in mind that what we know about the coronavirus today is mainly based on research performed before the outbreak of the omicron variant, and it is likely that this ever-changing virus will be around for a while. Therefore, continued research will be of utmost importance to keep up to date on COVID-19 in relation to rheumatic diseases, for optimal disease management.
References
1. Grainger et al. COVID-19 in people with rheumatic diseases: risks, outcomes, treatment considerations. Nat Rev Rheumatol. 2022 Apr;18(4):191-204.
2. Topless et al. Gout, rheumatoid arthritis, and the risk of death related to coronavirus disease 2019: an analysis of the UK Biobank. ACR Open Rheumatol. 2021 May;3(5):333-340.
3. England et al. Risk of COVID-19 in rheumatoid arthritis: a National Veterans Affairs matched cohort study in at-risk individuals. Arthritis Rheumatol. 2021 Dec;73(12):2179-2188.
4. Conway, R. et al. SARS- CoV-2 infection and COVID-19 outcomes in rheumatic disease: a systematic literature review and meta-analysis. Arthritis Rheumatol. 2022 May;74(5):766-775.
5. Reilev et al. Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT- PCR test for SARS- CoV-2 in Denmark: a nationwide cohort. Int J Epidemiol. 2020 Oct 1;49(5):1468-1481.
6. Strangfeld et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician- reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.
7. Robinson et al. The potential for repurposing anti-TNF as a therapy for the treatment of COVID-19. Med (N Y) 2020 Dec 18;1(1):90-102.
8. Curtis et al. American College of Rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases: version 4. Arthritis Rheumatol. 2022 May;74(5):e21-e36
9. Landewé et al. EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS- CoV-2: the November 2021 update. Ann Rheum Dis. 2022 Fib 23;annrheumdis-2021-222006.
10. Long et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020 Jun;26(6):845-848.
11. Krammer. SARS-CoV-2 vaccines in development. Nature 2020 Oct;586(7830):516-527.
12. Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021 Jul;27(7):1205-1211.
13. Tenforde et al. Effectiveness of SARS-CoV-2 mRNA vaccines for preventing Covid-19 hospitalizations in the United States. Clin Infect Dis. 2021 Aug 6;ciab687.
14. Geisen et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021 Oct;80(10):1306-1311.
15. Furer et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann Rheum Dis. 2021 Oct;80(10):1330-1338.
16. Connolly et al. Absence of humoral response after two-dose SARS- CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases: a case series. Ann Intern Med. 2021 174, 1332–1334.
17. Bonelli et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial. Ann Rheum Dis. 2022 May;81(5):687-694.
18. Braun-Moscovici et al. Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS- CoV-2. Ann Rheum Dis. 2021 Oct;80(10):1317–1321.
19. Machado et al. Safety of vaccination against SARS- CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician- reported registry. Ann Rheum Dis. 2022 May;81(5):695-709.