D.R.E.S.S. and COVID-19
Many DRESS patients and survivors are understandably anxious about the safety of SARS-CoV-2-Vaccines. We are here to help bring you scientific, evidence based information so that you can make the best decisions for yourselves and loved-one. Fortunately, we have guidance from DRESS Syndrome expert, Dr. Elizabeth Phillips who serves as our lead scientific advisor at the DRESS Syndrome Foundation. Dr. Phillips heads a research team at Vanderbilt University Medical Center that specializes in personalized medicine and the study of severe adverse drug reactions. Following is a piece she has written about the vaccines for our DRESS community. This is updated on a regular basis. We hope it helps.
If you are a DRESS patient and have already had one or both doses of a COVID-19 vaccine, please share your experience with us here: Vaccine Survey
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) During the COVID-19 Pandemic and SARS-CoV-2 Vaccines
Importance of vaccines in fighting the COVID-19 pandemic
Currently it is estimated that a significant proportion of the US and global population is still susceptible to infection with SARS-CoV-2 which leaves a population vulnerable to a considerable amount of morbidity and mortality. We cannot rely on our communities at large becoming immune to SARS-CoV-2 as a result of natural infection (herd immunity). Vaccines have the promise to be game changers in the fight against COVID-19, however high uptake in the population will be necessary to make a dent in the number of cases in the community, the number of hospitalizations and the number of deaths. Maintenance of social distancing, masking and routine infection control measures such as handwashing will continue be necessary and the mainstay in the short to medium term after the initiation of national vaccination programs. In addition all of the vaccine studies to-date have been carried out in adults with safety and efficacy in children yet to be established. Children have been known to be have less severe illness associated with COVID-19 including infection without symptoms. Children still readily develop and transmit SARS-CoV-2 and they will also be amongst the last to be vaccinated. Pregnant women have also not been included in the current SARS-CoV-2 vaccine studies and vaccine studies will soon be conducted in women in the second and third trimester of pregnancy. There is currently data in V-safe from over 77,000 participants who have indicated they were pregnant at the time of COVID-19 vaccination. Currently vaccination is recommended during pregnancy if the woman is part of a group currently recommended to receive the COVID-19 vaccine.
What has been involved in the development of the SARS-CoV-2 vaccines?
In the wake of the COVID-19 pandemic development of diagnostic testing, new drugs and vaccines have all been expedited. The process of developing vaccines which would normally take several years had been fast-tracked over several months. Fortunately, attention to safety has not been sacrificed, and at every step the Food and Drug Administration, the Centers for Disease Control, and independent safety monitoring committees have been involved in reviewing the data, making sure the vaccine is safe before progressing to the next stage. This included early studies in animals that led to the first in human studies that more critically looked at the safety and immune response and the final phase III studies that randomized patients to either receive the vaccine or a placebo (either saline or the inactive ingredients in the vaccine preparation). The Phase III studies are the most important studies to measure the actual efficacy of the vaccine which is the reduction in COVID-19 infections in those who received the vaccine versus those who received placebo. These studies have involved between 30,000 to over 40,000 participants.
Currently there are more than 40 vaccines being studied to prevent SARS-CoV-2 infection. An updated list of vaccine candidates can be found Here at this World Health Organization (WHO) website.
How have the vaccines been made?
The SARS-CoV-2 virus, like other coronaviruses to which it is closely related (SARS-CoV and MERS), has a large spike protein that extends out from the surface of the virus and is the major mechanism by which the viruses attach and enter human cells. The spike protein also represents the major target or construct from which vaccines have been designed, since antibodies that are induced against the spike protein can prevent SARS-CoV-2 from attaching to and infecting human cells. However, there are a number different technologies involved in making vaccines designed against the spike protein.
What is the current state of vaccine research and how close are we to having a vaccine that will be administered to the population?
During emergency situations like the current COVID-19 pandemic, the FDA is able approve the use of tests, treatments, and vaccines under an emergency use authorization (EUA). The FDA will only issue an EUA if there is evidence of safety and effectiveness of the vaccine and this includes at least 2 months of follow-up data available on 50% of the vaccine recipients.
Currently there are three vaccines made by the companies, Pfizer, Moderna and Janssen that have been given an EUA. Prior to the EUA being issued, the vaccine efficacy and safety of each of these vaccines must also be reviewed by an advisory committee to the FDA called the Vaccine and Related Biologic Products Advisory Committee. (VRBPAC). However the ultimate decision on whether to extend an EUA is determined by the FDA The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) is the committee that makes the ultimate recommendations for use of the vaccine, the recommended schedule and the groups who will be prioritized for SARS-CoV-2 vaccinations.
What is the experience of COVID-19 vaccines in the United States?
The Pfizer and Moderna vaccines have now been distributed broadly in the United states. These vaccines are administered as two intramuscular injections spread 3 and 4 weeks apart respectively. The Janssen (J&J) vaccine is given as a single dose intramuscular injection. As of April 12, 2021 there have been 187 million doses administered and almost 73 million individuals vaccinated in the United States.
What side effects are associated with the SARS-CoV-2 vaccines?
SARS-Cov-2 vaccines have been associated with mild to moderate but short-lived symptoms that occur within 24-48 hours after vaccination. These include fever, chills, headache, muscle and joint pain and short-term fatigue that occurs in approximately 10% of vaccine recipients. These symptoms appear to be worse after the second injection. Injection site reactions are common with both vaccines, appear to be slightly more enhanced with the Moderna vaccine and worse after the second dose. Anaphyalxis (an immediate allergic reaction not related to SJS) has been described to occur in approximately 4.5 per million doses of the Pfizer vaccine and 2.5 per million of the Moderna vaccines. Rare cases of anaphylaxis have been reported with the Janssen and Astra Zeneca vaccines. The Janssen single dose vaccine and the Astra Zeneca vaccine (not available in the US) are viral vector vaccines. The Astra Zeneca vaccine is currently being investigated for a possible associated with clotting events that also are thought to occur rarely in < 3 per million doses (vaccine induced immune thrombotic thrombocytopenia).
Currently 7 million doses of the Janssen vaccine have been administered in the US with a current pause on vaccination while the clotting events are being investigated. Click Here for more information on common side effects associated with the COVID-19 vaccines and some helpful tips.
Is there a cost associated with the SARS-CoV-2 vaccines?
The SARS-CoV-2 vaccine will be offered free of charge to all insured and uninsured individuals based on ACIP recommendations.
What processes are in place to monitor the ongoing safety and efficacy of the SARS-CoV-2 vaccines?
The EUA is issued based on the phase III clinical trial data but the FDA will mandate careful studies after the EUA is issued. In addition, since it is not known how long protection from the SARS-CoV-2 vaccine will last, whether it will prevent transmission in the community and how well it works in populations that have not been studied. Processes are also in place to monitor post-EUA safety and effectiveness of the of the SARS-CoV-2 vaccine through the individual pharmaceutical companies and the CDC.
Should a patient who currently has DRESS or is a DRESS survivor have any concerns about receiving a SARS-CoV-2 vaccine?
The SARS-CoV-2 vaccines to-date have been safe and efficacious in the populations that they have been studied which include adults >65 years of age. The vaccine induces a predictable immune response against the SARS-CoV-2 spike protein that does not lead to the hyperinflammatory environment seen in some patients with acute COVID-19 disease. It would thus be predicted that dosing of the SARS-CoV-2 vaccines would be safer for current or past DRESS patients than going through acute SARS-CoV-2 clinical illness which in moderate to severe disease is associated with activation of the immune system and release of cytokines that lead to a proinflammatory and hypercoagulable state. In addition to the inflammation associated with acute COVID-19 illness rarely a multi-inflammatory syndrome has been described more commonly in children (MIS-C) than adults (MIS-A) that occurs 2-4 weeks following acute COVID-19 illness. This has not been described following vaccination.
It is also much easier to treat mild to moderate vaccine related side-effects than it is to treat moderate to severe COVID-19. The immune response to the SARS-CoV-2 vaccine has not been studied in immunocompromised patients or those on high dose steroids and this will need to be evaluated. However, there are a number of studies of other vaccines in this population and immune responses have not been impacted greatly.
It is recommended that the administration of live-attenuated vaccines be deferred in patients on steroids > 10 mg prednisone equivalent for greater than 2 weeks until 3 months following steroid discontinuation. (e.g. measles/mumps/rubella(MMR) or chickenpox (Varicella) vaccines). The current SARS-CoV-2 vaccines in late stage studies likely to receive EUA in the near future do not contain live virus products.
It is understandable that survivors of DRESS would be hesitant to take drugs and vaccines even outside the drug that was implicated in their reaction given the randomness and severity of the disease. However, DRESS patients can be reassured that receiving the SARS-CoV-2 vaccine is a safer option than natural infection.
Currently there have been two reports of anaphylaxis associated with the Pfizer vaccine in the United Kingdom which as of December 9. Anaphylaxis suspected due to the SARS-CoV-2 vaccine has now been described in approximately 21 individuals out of approximately 1.8 million doses administered or approximately 11.5 per million doses administered. This is considered very uncommon although it appears to be up to 10 fold more common than other licensed vaccines. Currently it is not known what is driving this or what the mechanism is. Part of the carrier vehicle for the active part of the vaccine or mRNA is made of polyethylene glycol (PEG2000) a component of both the Moderna and the Pfizer-BioNTech vaccines. PEG has rarely been associated with anaphylaxis and one hypothesis is that it could be the component driving the rare cases of anaphylaxis that have been seen with the mRNA vaccines.
There is no association between anaphylaxis and DRESS either in clinical presentation or mechanism. Anaphylaxis is an immediate reaction that occurs within 30 minutes of vaccine injection and is associated with multiple symptoms that progress rapidly together including hives, flushing, itching, swelling of the face tongue and difficulty swallowing, shortness of breath or wheezing, low blood pressure, fast heart rate and nausea and vomiting. The treatment for anaphylaxis is epinephrine and if it is treated rapidly it is completely reversible without any long-term effects. If anaphylaxis does occur it is possible this is due to one of the excipients (inactive ingredients) in the vaccine such as PEG of which there is no association with these excipients and DRESS.
Otherwise there have been no described unusual immunological illnesses, rashes or severe allergic reactions described associated with the SARS-CoV-2 vaccines studied to-date. Although rare immunological events maybe reported in the future under the scrutiny of post-licensure vaccine safety programs there is no reason to believe that patients who have experienced DRESS would be at higher risk for these events. The genetic factors predisposing to DRESS are specific for a specific drug or chemically related drugs and there is no reason to believe these predisposing factors would increase the risk of an adverse reaction to a SARS-CoV-2 vaccine.
Currently there are only two main safety reasons in adults not to get the COVID-19 mRNA vaccine: 1) known immediate or severe reaction to a component of the vaccine (e.g. PEG and PEG derivatives such as polysorbates) 2) Severe or immediate reaction associated with the first dose of the COVID-19 mRNA vaccine. In the case of (2) although the advice is currently not to get the second dose some patients may experience milder symptoms such as hives. If reactions occur to the vaccine it is recommended to see an allergist who can do specialty testing and do risk assessment as to best future management.
In summary: History of DRESS is not a reason not to get the vaccine. DRESS is not associated with allergy to PEG or PEG derivatives (PEG allergy).
If I have a safety reason that prevents me from getting a COVID-19 mRNA vaccine is it safe for me to get the Janssen (Johnson & Johnson) vaccine?
The J&J vaccine is a single dose vaccine that is viral vector vaccine also based on the spike protein construct. The J&J vaccine does not contain PEG but does contain polysorbate which is closely related to PEG. If you have had previous anaphylaxis associated with a vaccine or injectable drug or have had anaphylaxis to a PEG product you should talk with your doctor who may refer you to a specialist to determine if it is safe for you to get the J&J vaccine.
In the near future there will be additional vaccines available in the United States and this page will be updated accordingly.
What if I currently have DRESS and I get COVID-19 Infection?
In general you can expect the course of COVID disease to run as usual. If you are on high dose steroids and/or other immunosuppressants you may be at higher risk with COVID-19 infection or at risk for having a delayed protective immune response. Currently monoclonal antibodies to COVID-19 are being offered to individuals who are on immunosuppressants when they develop infection with COVID-19 and you should discuss this with your provider. COVID-19 monoclonal antibodies if given to higher risk individuals early in infection may show benefit for recovery.
If you have had recent monoclonal antibody therapy for COVID-19 (products by Regeneron and Lilly) you should also wait 90 days before getting vaccinated.
If an SJS/TEN patient got sick with COVID-19 there is no contraindication to giving anti-viral therapy such as remdesivir or steroids such as dexamethasone.
Regardless of which COVID-19 vaccine you receive please also sign up for V-safe which is a smartphone application designed to remind you to get your second dose and track potential vaccine related side effects (https://cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe.html)
Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Eng J Med 2020 Dec 30: NEJMra20335343. Click here for a link to article.