The immune system is designed to protect the body against infection. However, an immune response that is too strong can have severe consequences. In people living with lupus, their immune system is hyper-aggressive, working against itself and creating antibodies that attack organs and tissue. In some patients infected with the novel coronavirus that causes COVID-19, the immune system can also react in an extremely chaotic way, resulting in severe inflammation and damage to organs and tissue – much like the damage lupus and other autoimmune disorders can exact on people. There are undeniable parallels between lupus and COVID-19, and we’re hoping that understanding one can better prepare us to understand and treat the other.
Mini-Classes with Shayla Shorter, Ph.D.
Our own Dr. Shayla Shorter, Scientific Program Manager at the Lupus Research Alliance explains how research on lupus and on COVID-19 can help understand both diseases in a series of videotaped mini classes. Click here or on the video below to sit in on the first class:
Posted May 6, 2020
How the Immune System Fights Back
Introduction to the immune system including how it normally works.
Posted May 13, 2020
What Happens When the Immune System Overreacts?
Explains autoimmunity (lupus) and immunopathology (severe COVID-19) and the connections between the two.
Posted May 26, 2020
Why Drugs for Lupus May Work Against COVID-19
Why drugs used for autoimmunity might be helpful in treating COVID-19. Explains different classes of drugs and how they work as well as the value of repurposing drugs for different uses.
Posted May 27, 2020
Research Holds the Answers
Why studying lupus helps us understand the immune system and the implications for our understanding of other diseases.
When the immune system works correctly, it reacts to a pathogen with just the right level of response. If the immune system doesn’t work well enough, the pathogen wins and overcomes the body. But if it is too strong, the immune system sends out too many signals using chemical messengers called cytokines to fight the infection and causes too much inflammation that damages nearby organs.
Overactive immune responses are characteristic of people with lupus and other inflammatory rheumatic diseases as well as severe cases those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). That is why many of the drugs used to treat lupus and other autoimmune diseases such as rheumatoid arthritis may help treat hospitalized patients who have developed serious COVID-19 in response to exposure to this specific coronavirus.
Anti-inflammatory Drugs that May be Repurposed for COVID-19
Tocilizumab (Actemera®). Phase 3 clinical trial results published in the New England Journal of Medicine January, 2021 showed that the drug tocilizumab reduced the likelihood of COVID-19 pneumonia progressing to mechanical ventilation or death but did not improve survival.[i] Study investigators hypothesize that “patients who had progression to mechanical ventilation after receiving tocilizumab may compose a subgroup of patients with more severe disease and therefore a higher risk of death; this hypothesis is supported by the fact that a larger percentage of patients in the placebo group than in the tocilizumab group died without receiving mechanical ventilation. Studies are under way to address this question further.”
An immunosuppressant, tocilizumab is approved by the U.S. Food and Drug Administration for moderate to severe rheumatoid arthritis and other inflammatory diseases. Tociluzumab blocks or inhibits the receptor of interleukin 6 (IL-6) that promotes inflammation. The pharmaceutical company Genentech conducted the trial to see if tocilizumab could improve outcomes in pneumonia caused by COVID-19.
Sarilumab (Kezvara®). Another IL-6 inhibitor, sarilumab, was also tested in a Phase 3 clinical trial for treating pneumonia caused by COVID-19. Kezvara is approved by the U.S. Food and Drug Administration to treat moderate to severe rheumatoid arthritis after a disease-modifying agent was tried. When added to usual hospital care among severely or critically ill hospitalized COVID-19 patients, Kezvara lowered the length of hospital stay and sped up the time it took for improved symptoms – but not with statistical significance. As of September, 2020, study sponsors Sanofi and Regeneron did not anticipate conducting further clinical studies for Kevzara in COVID-19.[ii]
Auranofin (Ridaura®). Approved by the FDA for rheumatoid arthritis, auranofin is also being looked at by researchers as a potential treatment for the coronavirus. Another disease-modifying agent, auranofin seems to interfere with the ability of the virus to replicate – make copies of itself, so the virus cannot spread through the body. As in rheumatic diseases, auranofin decreases inflammation. Results of a pilot study conducted in German in September 2020 suggested further evaluation of auranofin and others in the same drug class as SARS-CoV antiviral drugs.[iii] Earlier in 2020, a group of scientists at Georgia State University published their results looking at the drug. They found that treatment with auranofin dramatically reduced viral RNA and the release of cytokines that promote inflammation. They concluded that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury.[iv]
Baricitinib (Olumiant) is a Janus Kinase (JAK) inhibitor approved by the FDA to treat moderate to severe rheumatoid arthritis. It received Emergency Use Authorization by the FDA for the treatment of hospitalized patients with COVID-19 because of its ability to lessen inflammation. This authorization is based on data from the multicenter, randomized, controlled, blinded ACTT-2 clinical study conducted by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. Results showed that compared with the investigational remdesivir, baricitinib reduced recovery time, improved clinical status, lowered the proportion of patients who required ventilation, lessened death and reduced adverse events. The oral JAK inhibitor, baricitinib is approved in the U.S. and EU as a treatment for adults with moderate to severe rheumatoid arthritis.[v]
Chloroquine and Hydroxychloroquine. These antimalarial, anti-rheumatic drugs are commonly used as disease-modifying agents that lessen inflammation in lupus, rheumatoid arthritis and some skin diseases. Early in the COVID-19 pandemic, a couple of small studies suggested that chloroquine and the less toxic hydroxychloroquine (known by the brand name Plaquenil) disrupt the ability of the coronavirus to enter and reproduce in human cells. Numerous clinical trials tested hydroxychloroquine among patients with severe COVID-19 in the hospital; ultimately results showed no benefit from hydroxychloroquine and the FDA warns against its use for COVID-19.
[i] Gardiz-Diaz J., et al. Tocilizumab in patients hospitalized with COVID-19 pneumonia. N Engl J Med 2021; 384:20-30. Accessed at: https://www.nejm.org/doi/10.1056/NEJMoa2030340.
[ii] Sanofi provides update on Kevzara® (sarilumab) Phase 3 trial in severe and critically ill COVID-19 patients outside the U.S.. Press Release September 01, 2020. Accessed at: https://www.sanofi.com/en/media-room/press-releases/2020/2020-09-01-07-00-00.
[iii] Ott I. Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike‐ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics. 11 September 2020. https://doi.org/10.1002/chem.202004112.
[iv] Kumar M. The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells. Virology doi: 10.1016/j.virol.2020.05.002
[v] Baricitinib Receives Emergency Use Authorization from the FDA for the Treatment of Hospitalized Patients with COVID-19. Press Release November 19, 2020. Eli Lilly and Company. Accessed at: https://investor.lilly.com/news-releases/news-release-details/baricitinib-receives-emergency-use-authorization-fda-treatment.
What is COVID-19?
In December 2019, a new virus called SARS-COV-2 was identified in Wuhan, China. This virus was found to cause a severe respiratory illness in patients which was later named after the type of virus that caused it and the year it was identified (coronavirus disease 2019 or COVID-19).
Should people with lupus be especially concerned about COVID-19?
People with lupus are predisposed (at greater risk) to infections because of their disease as well as the medications they take to manage it. Click here for information from the U.S. Centers for Disease Control and Prevention (CDC), the American College of Rheumatology and other resources.
Are people with lupus immunocompromised?
People with lupus are considered immunocompromised and so could be at greater risk for infections in general because of their underlying disease itself and some of the medications they take to treat lupus. Click here for information from the CDC for people who are at risk.
Are people who are taking immunosuppressive medications more susceptible to infections such as COVID-19?
People taking immunosuppressive medications are considered to be immunocompromised and so could be at greater risk for infections in general. It’s best to consult with your healthcare professional for specific recommendations. You should not stop or alter your medications without consulting with your rheumatologist first. Not all people with lupus take immunosuppressive medications.
Currently, there is no specific data on the virus causing COVID-19 in patients with lupus. Thus, the rate and the severity of the infection in lupus patients is not yet known.
The CDC recommends that people at high risk:
- Stay home and avoid crowds as much as possible to further reduce your risk of being exposed. Also avoid non-essential travel.
- Have supplies on hand, including medications you normally take.
- When going out in public, keep away from others who are sick, wear a face mask, limit close social contact and wash hands often.
Are the new vaccines for COVID-19 safe for people with lupus?
The critical question for the lupus community is which new vaccine will be most appropriate for lupus patients. To address this question, the LRA recently convened a meeting attended by experts in vaccinology, immunology, and rheumatology as well as representatives from the LRA Research Committee, the National Institutes of Health (NIH), and the American College of Rheumatology. The consensus was that the vaccines were almost certainly all safe for lupus patients but that in the long run, some may be more efficacious for lupus patients than others. Recently, our Trustees approved a $3 million project to explore how the new vaccine platforms might impact people with lupus. Meanwhile.our best advice is for patients to make a decision about this (and all treatment issues) in collaboration with their rheumatologists.
What technology do the new vaccines use?
Three types of vaccines are being tested to protect against COVID-19. They use different technologies, but each is designed to help the body fight the virus without getting sick.
- Messenger RNA (mRNA) vaccines contain genetic material from SARS-CoV-2 (the virus that causes COVID-19). Our cells use the genetic material to manufacture small pieces of the virus that teach the immune system to attack SARS-CoV-2. These pieces are part of the “spike” protein that cover the surface of the virus and allow it to attach to and enter human cells. The mRNA vaccines allow cells of the immune system known as B cells to produce molecules called antibodies that stop the spike protein from attaching to human cells. By blocking the attachment of the virus to human cells, the antibodies help prevent cells from getting infected with the virus. mRNA vaccines have been in development for years, but the Pfizer/BioNTech and Moderna vaccine are the first to complete all stages of drug development and receive approval under Emergency Use Authorization. Four other companies are also making mRNA vaccines for COVID-19.
- Adenovirus-vector vaccines contain a weakened version of a cold virus called adenovirus. The adenovirus acts as a vector (or carrier) of DNA genetic material for the spike protein from SARS-CoV-2. Once the adenovirus vector is inside our cells, the DNA tells our cells to produce spike proteins. The spike proteins prompt B cells to make antibodies that fight the virus if we become infected in the future. Adenovirus-vector vaccines are being developed by Johnson & Johnson/Janssen, Oxford-AstraZeneca, and other companies.
- Protein subunit vaccines include fragments of the spike protein from SARS-CoV-2 to help our immune system recognize the spike protein as non-human. The vaccines are made with chemicals called adjuvants that boost their effectiveness. B cells then develop antibodies to the spike protein to help prevent SARS-CoV-2 from infecting our cells. This helps prevent severe illness from COVID-19. Protein subunit vaccines are being developed by Novavax, Sanofi/GSK, and other companies.
How do I get a vaccine for COVID-19?
As of January 19, 2021, vaccine distribution is being directed by state governments. Start the search for a vaccine appointment by visiting your state’s official website – usually the address is www.[STATE NAME].gov or you can google your state government and it should come up.
Will people with lupus be given special consideration as people with a pre-existing condition?
Each state has its own guidelines for who is given priority to be vaccinated against COVID-19. Check your state’s government website to see eligibility guidelines.
Are there treatments in development for COVID-19?
A number of drugs are being looked at as potential treatments for COVID-19, including many commonly used to treat rheumatic diseases such as lupus and|or rheumatoid arthritis. Click here to learn more.
Early in the pandemic, some researchers believed that a drug commonly taken by people with lupus and other autoimmune diseases, hydroxychloroquine (Plaquenil) would help treat or prevent COVID-19. However, data proved that hydroxychloroquine is not effective for treating or preventing COVID-19.
Why are drugs for lupus and rheumatoid arthritis being considered for COVID-19?
Overactive immune responses are characteristic of people with lupus and other inflammatory rheumatic diseases as well as severe cases of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). That is why many of the drugs used to treat lupus and other autoimmune diseases such as rheumatoid arthritis may help treat hospitalized patients who have developed serious COVID-19 in response to exposure to this specific coronavirus.
- Asymptomatic – producing or showing no symptoms
- Community spread – means people have been infected with the same pathogen in a specific geographic area, including some who are not sure how or where they became infected.
- Coronavirus – a family of viruses that can cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).
- COVID-19 – abbreviation of “Coronavirus disease 2019”, a disease caused by a new coronavirus identified in 2019 called SARS-COV-2. In COVID-19, ‘CO’ stands for ‘corona,’ ‘VI’ for ‘virus,’ and ‘D’ for disease.
- Cytokine – small signaling proteins which are secreted by certain cells of the immune system and have an effect on other cells. (Examples: interferon, interleukin, and growth factors)
- Cytokine Storm – a severe immune reaction in which the body releases many cytokines into the blood too quickly, causing inflammation and damage to organs.
- Inflammation – a response that occurs when tissues are injured. The damaged tissues release chemicals that cause blood vessels to leak fluid into the tissues, causing swelling and heat.
- Immunopathology – unintended damage to body tissues caused by an immune response to an infection.
- Interleukin – a cytokine or signaling protein produced by immune cells for regulating immune responses.
- Prophylactic – intended to prevent disease.
- SARS-COV-2 – an abbreviation for “severe acute respiratory syndrome-coronavirus-2”. A virus identified in 2019 that causes a respiratory illness called COVID-19
Sources: U.S. Centers for Disease Control, National Institutes of Health, World Health Organization, Oxford Dictionaries