• SJS survivors should be reassured that there is no evidence of an association between the COVID-19 vaccines and SJS/TEN. COVID-19 natural infection has been associated with erythema multiforme, which is an SJS/TEN-like illness. Delayed rashes that have been related to COVID-19 vaccines when occurring on the first dose of an mRNA vaccine have uncommonly occurred on the second. This suggests that this is the body’s immune response to the active components of the vaccine rather than an allergic response.
• Currently, there is no reason to exclude anyone who has had SJS in the past from a COVID-19 vaccine. Many SJS survivors have had long-term sequelae and even lung involvement, and it is essential to be protected from COVID.
Quotes from SJS survivors who are completely vaccinated and very relieved to have done so:
❖ ” I was nervous, as I am sure many SJS survivors are, but the thought of getting the virus itself scared me more.”
❖ “I was a little sore and had a headache for a day or two, but otherwise was fine! I had no rash or reaction in my eyes, which is something I’ve struggled with throughout the year following my SJS diagnosis. I am scheduled to receive the second dose on Tuesday. Overall, I am very happy I chose to receive the vaccine. I’ve struggled with a long-term cough and congestion for the last year, so I have been very worried about COVID complications.”
❖ “I was vaccinated during pregnancy at 20 weeks. I made this decision based on the information from my immunologist, who is an SJS specialist. The risks for getting COVID are FAR greater than any adverse reaction to a vaccine.
❖ “I am so thankful I did with the variants exploding in this country with a newborn at home. I feel like it is not only my responsivity to do everything I can to keep myself (I am immunocompromised after SJS) and my baby safe.”
❖ “As an SJS survivor, a mom of a child with a medical condition, and a second grade teacher, I knew I wanted not only to protect myself but my family and students. To be honest, I was a nervous wreck, and I wasn’t sure how my body would react. However, after receiving both vaccinations, the only side effects I experienced were a headache, having a fever, and being more tired than usual but after a good night’s rest, it went away.
❖ “As an SJS survivor, I would much rather have the vaccination than try to be treated for Covid and have to have an antibiotic. I am truly thankful that I was able to get vaccinated and would recommend it to any of my fellow SJS survivors and their families. The only way we are going to stop this horrible pandemic is to get vaccinated.”
COMMON QUESTIONS AND ANSWERS ABOUT SJS/TEN COVID-19 and VACCINES:
I have had SJS/TEN related to a drug and have avoided all drugs and vaccines since then. What are my chances of getting SJS/TEN again?
- Fortunately, getting SJS/TEN a second time if you avoid the original drug that you took and all structurally related drugs is a lower probability than lightning striking twice. Several unfortunate events had to align for you to get SJS/TEN, including genetics, past viral infections history, and the specific drug you took. There is no component of any vaccine on the market that looks the same as a drug or any of the drugs known to cause SJS/TEN. Polyethylene glycol in its pure form does not cause SJS/TEN and does not cross-react with other drugs known to cause SJS/TEN. Getting natural infection with COVID can lead to complications including bacterial infections and pneumonia. If you have had SJS/TEN related to an antibiotic in the past this could put you at risk for inferior antibiotic choices. In addition, if SJS/TEN affected your respiratory tract, the affect of COVID could cause further damage. Overwhelmingly the safest thing to do is to take the COVID vaccines.
What if I don’t know what caused my SJS/TEN?
- This is sometimes called Mycoplasma induced rash and mucositis or reactive infectious mucocutaneous eruption. More recently, it has been proposed that this be called “SJS-like illness.” It occurs more commonly in children where SJS/TEN can be caused by an infectious exposure. If no drug cause can be identified for SJS/TEN it may have been reactive to an infectious agent. When this happens, the most common situation would be for it to happen once and never again. Some of these may be recurrent due to Mycoplasma or another agent and this is not well understood. Introduction of a vaccine to a virus that your immune system has not seen before however would not be a risk factor here. If anything, vaccination would protect your immune system from the overload that occurs during natural COVID infection and protects other organs and your lungs that could be hit during natural COVID infection and may have been damaged during SJS/TEN. The same applies if it is thought that you had SJS/TEN related to a different type of vaccine. Because COVID is a new virus in our community and the proteins (antigens) are new, there is no cross-reactivity between the COVID vaccines and your previous vaccine (e.g., influenza).
How much experience is there with the COVID vaccines? It seems like they were put together very quickly. Is this not a risk for me and others?
- Worldwide more almost 5 billion individuals as of August 26, 2021, have received at least one shot of a COVID-19 vaccine. This is an unprecedented effort and represents nearly 50% of the world’s population. Additionally, of November 23, 2021, 73.9% of individuals in the United States have received at least one dose of the COVID-19 vaccine. Although these vaccines such as the mRNA (like Moderna and Pfizer) and adenoviral vector vaccines (like Johnson and Johnson and AstraZeneca) have never been used in the routine vaccine setting, there has already been more than two decades that has gone into making these vaccine constructs. This means that they are not new and amazing degree of research had already gone into their development well before COVID-19. These vaccines went through long years development and testing in animals before they underwent early trials in humans for viruses of global importance such as Ebola. In the midst of the pandemic we reaped an enormous benefit from these arduous efforts which allowed the COVID-19 vaccine effort to be rolled out very quickly.
How have the COVID 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 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.
- The current vaccines in the US such as the mRNA vaccines and viral vector vaccines are remarkable for the ease at which they can be modified to be more active against viral variants.
- 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.
When will the current COVID -19 vaccines receive a full license and what is the purpose of an emergency use authorization?
- 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 two 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 in the United States. 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.
- As of August 23, 2021 the Pfizer-BioNTech vaccine is now fully licensed by the US FDA.
Why are vaccines important in helping to control and end the COVID-19 pandemic?
- Although there are many tools instrumental in stopping a pandemic vaccines are key in reducing the associated morbidity and mortality. This is true even when viral variants emerge in the community to which vaccines may be less active like the current Delta variant. This is because vaccines not only protect against the acquisition of infection and the replication of the virus in the community they actually protect against the severity of infection. In the month of June 2021 alone, over 99% of those hospitalized for COVID-19 were unvaccinated. As time ellapses and new variants emerge in the community it is true that individuals are more likely to get infected with COVID however they are likely to have mild illness with a significantly shortened time over which they are actually infectious. This means that vaccination limits morbidity and mortality in and individual and curtails spread in the population. Curtailing replication and spread of COVID-19 in the population is also key to prevention of the emergence of more variants to which vaccines may not work as well.
What side effects and toxicities are associated with the COVID-19 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 can occur to some extent in up to 50% of those receiving vaccination. These symptoms appear to be worse after the second injection in those who have not previously had natural infection with COVID. Injection site reactions are common with both vaccines, appear to be slightly more enhanced with the Moderna vaccine and worse after the second dose. Simlar side effects have been seen with booster injections of the vaccines. 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. None of the vaccines have been directly associated with SJS/TEN. Erythema multiforme an illness that can mimic SJS/TEN and is associated with viral illnesses has been reported to occur in conjunction with natural infection with COVID-19. Erythema multiforme has rarely occurred in associated with COVID-19 vaccines however <50% of those who have experienced this after dose 1 of the mRNA vaccines have experienced a repeat episode after dose 2. Acute generalized exanthematous pustulosis (AGEP), a cutaneous eruption associated with drugs, vaccines and viruses, but with out any associated mortality or long-term morbidity has been associated with the Astra Zeneca and Johnson & Johnson viral vector vaccines.
- The Janssen single dose vaccine and the Astra Zeneca vaccine (not available in the US) are viral vector vaccines. As of July 25, 2021 over 13 million doses of the Janssen vaccine had been administered in the US. he Astra Zeneca vaccine and Janssen vaccines (J&J) are currently being investigated further for clotting events (see thrombosis with thrombocytopenia – TTS below) that also are thought to occur rarely. Following a 10 day pause on vaccination that was initiated to investigate clotting events that had occurred similar to the events occurring with Astra Zeneca vaccination with Janssen was resinstituted. Thrombosis (clotting) with thrombocytopenia (low platelets) also known as TTS have occurred within 4-30 days following vaccination with a viral vector vaccination. All cases have occurred in those under 65. The risk to women aged 18-49 is approximate 7 TTS cases per million doses. It is much lower for men and women outside of this age group estimated to be <1/million). There is insufficient data in those < 18 for whom the vaccine is currently not approved. The pause on the Janssen (J&J) vaccine was released after review by the CDC and FDA and the Janssen (J&J) vaccine is currently given emergency use access for those over 18. Warning language included with the Janssen vaccine is that it has in rare instances caused TTS in women under the age of 50. There is no association between these clotting events and SJS/TEN or other types of drug hypersensitivity. Additional information can be found at: https://hematology.org/…/vaccine-induced-immune….
- A prominent type of organ dysfunction associated with COVID-19 natural infection has been myocarditis (inflammation around the heart). It has also been noted that myocarditis can more rarely occur after COVID-19 mRNA vaccination. This has been noted to occur more commonly in males under 30 and after the second dose of the Pfizer-BioNtech and Moderna vaccines. These cases have been mild and responded to anti-inflammatory medications such as non-steroidal anti-inflammatory drugs (NSAIDS) in most cases.
- 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 COVID-19 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.
Does Rash Occur in Association with COVID-19 Illness and Can this be Confused with SJS/TEN?
- Approximately one in give people will develop a skin rash in associated with COVID-19 illness. These rashes are generally either hives, measles like (erythematous rash) or COVID fingers or toes (chilblains) that presents with reddish purplish bumps on the fingers and toes. The latter appears more common in children and young adults and appears related to damage of the lining of vessels. Erythema multiforme (EM), a disease typically triggered by viral infection (most commonly Herpes simplex virus I) can be difficult to differentiate from SJS/TEN but is characterized by a more typical rash with target lesions (that resemble a bullseye) and distribution of rash that favors the extremities versus the truncal distribution characteristic of early SJS/TEN. In EM there is also less mucosal involvement and less common constitutional features such as fever and sore throat which are common prodromal symptoms of SJS/TEN. There have been case reports of EM in association with COVID-19 illness. Drug-induced SJS/TEN is related to a distinct genetic predisposition and would not be expected to predispose to COVID-19 related EM or other rashes.
Are there any reasons why a person who has recently experienced SJS/TEN or is a survivor of SJS/TEN have any concerns about receiving a COVID-19 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 SJS/TEN 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 SJS/TEN 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, those who have recently experienced SJS/TEN and survivors of SJS/TEN can be reassured that receiving the SARS-CoV-2 vaccine is a safer option than natural infection.
If I have had SJS am I at risk for Anaphylaxis?
- Reports of anaphylaxis occurred shortly after the rollout of the Pfizer-BioNtech mRNA vaccine in healthcare workers and on the first dose of the vaccine. This caused concern that a specific allergic reaction could be occurring to the PEG component of the mRNA vaccines. Over the last few months many who had immediate reactions to the first dose have gone onto tolerate the second dose with recommendations and expert guidance. Although there is not a clear mechanism associated with anaphylaxis with the mRNA vaccines it appears that these are uncommonly IgE-mediated reactions which would make individuals at risk to have a worse and life-threatening reaction with each and subsequent doses of vaccine. In fact, many such patients have tolerated the second dose of mRNA COVID-19 vaccines without any symptoms. Ongoing studies in the United States are looking at risk and mechanisms of anaphylaxis related to the mRNA vaccines. There is no association between anaphylaxis, which is an immediate reaction occurring within 30 minutes of dosing and SJS/TEN, as they are mechanistically disparate reactions. Anaphylaxis associated with mRNA vaccines appeared to occur at a rate of 2.5/million doses for the Moderna vaccine and 4.7/million for Pfizer.
- 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 SJS/TEN would be at higher risk for these events. The genetic factors predisposing to SJS/TEN 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.
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 vaccinee.
What are the implications for SJS/TEN if I get COVID-19 Infection?
- In general, you can expect the course of COVID disease to run as usual. If have had recent or acute SJS/TEN and have been 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, a cocktail of monoclonal antibodies to COVID-19 is 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.
Are antibody levels reliable to determine whether I need another shot or a booster shot of the COVID-19 vaccines?
SARS-CoV-2 antibody tests should NOT be the basis for a third dose determination. Antibody tests do not help define who is eligible for a third dose of a COVID-19 mRNA vaccine.
The indication for a third dose of an mRNA COVID-19 vaccine includes patients with moderate or severe immunocompromised state who have already received 2 doses of a mRNA COVID-19 vaccine (e.g., Pfizer-BioNTech or Moderna) with the 2nd dose at least 28 days ago AND immunosuppressive state such as:
• Under active treatment for cancer
• Transplant patient on drugs that dampen the immune system to prevent organ rejection.
• Bone marrow transplant in last 2 years
• Receipt of CART-cell therapy in last 2 years
• Primary immunodeficiency syndrome (Common Variable Immune Deficiency, DiGeorge Syndrome, Wiskott-Aldrich syndrome)
• Advanced (CD4<200) or untreated HIV infection
• Active treatment in the last month with a drug that dampens the immune system (this could be relevant to SJS/TEN or DRESS patients who have been recently treated or hospitalized)
o High dose corticosteroids (≥20mg prednisone or equivalent per day for ≥14 days)
o Specific chemotherapeutic agents that dampen the immune system (if in doubt ask your doctor) (ex: cyclophosphamide, temozolomide, chlorambucil, carboplatin, cisplatin. methotrexate, hydroxyurea, gemcitabine, fludarabine)
o Other drugs sometimes used to treat SJS/TEN and other autoimmune diseases, inflammatory bowel disease, rheumatoid arthritis etc. e.g. TNF alpha inhibitors (ex: adalimumab, etanercept, infliximab) or rituximab, anakinra, golimumab, natalizumab)
o If in doubt about a monoclonal antibody and whether it dampens your immune system, ask your doctor
o Select patients with other diseases that cause immunocompromise (e.g. end stage kidney disease on dialysis)
• As of September 17, 2021 the FDA approved the use of booster shots for COVID-19 vaccines for those that are at least 5 months from the primary series, are > 65 years of age or at risk for severe illness or exposure (immunocompromised (see above) or healthcare workers).
• Additionally as of November 19, 2021, the FDA has amended the emergency use authorizations for both Pfizer-BioNTech and Modernal COVID-19 vaccines authorizing use of a single booster dose for all individuals 18 years of age and older after completion of a primary vaccination with any FDA-authorized or approved COVID-19 vaccine
How many doses of COVID-19 vaccines have been given globally and in the USA?
- As of October 26, 2021 more than 6.89 billion doses of a COVID-19 vaccine have been given globally, including over 414 million doses in the US.
What about booster doses and who is eligible?
- A booster shot is considered to be an additional shot of the COVID-19 vaccines following primary vaccination. For the Pfizer-BioNTech and Moderna vaccines primary vaccination consists of two doses; for the Janssen (J&J) vaccine primary vaccination consisted of a single shot.
- As of November 19, 2021, the FDA has amended the emergency use authorizations for both Pfizer-BioNTech and Moderna COVID-19 vaccines authorizing use of a single booster dose for all individuals 18 years of age and older after completion of a primary vaccination with any DFA-authorized or approved COVID-19 vaccine
- A booster dose is the third shot of the Pfizer or Moderna vaccines administered at least 6 months from the primary vaccination or 2 months from the single shot primary vaccination of the J&J vaccine.
What about children and COVID-19 vaccines?
- The FDA has authorized emergency use of the Pfizer-BioNTech vaccine for children ages 5-17 years of age as of October 29, 2021. Children ages 12 years and older receive the same dosage as adults, and children ages 5-11 receive a smaller, age-appropriate dose of the vaccine.
- Studies have been done in children and some early data suggesting that the benefit of vaccination exceeds risk of COVID-19.
- There is no reason to exclude children who are SJS survivors from the COVID-19 vaccines. Children who survive SJS have a higher risk of bronchiolitis (a form of lung disease) and it is beneficial to be protected from COVID-19 illness.
Are there any other treatments aside from vaccination to help prevent COVID-19?
- On December 20,2021, the FDA authorized emergency use of the AstraZeneca Pharmaceuticals therapeutic EVUSHELDTM (tixagevimab co-packaged with cilgavimab) for the pre-exposure prophylaxis of COVID-19 in certain adults and children aged 12 and older.
- EVUSHELD may only be used in adults and pediatric individuals (12 years of age and older weighing at least 40 kg):
- Who are not currently infected with SARS-CoV-2 and have not had a recent exposure to an individual infected with SARS-CoV-2 and
- Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
- For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine(s) and/or COVID-19 vaccine component(s).
- EVUSHELD may only be used in adults and pediatric individuals (12 years of age and older weighing at least 40 kg):
- Importantly, regardless of the cause of SJS/TEN (e.g. drug, infection or other), a prior diagnosis of SJS/TEN by itself is NOT an appropriate use for EVUSHELD, EXCEPT in those individuals currently on sustained immunosuppressive therapy. Therefore, for the majority of individuals with a prior diagnosis of SJS/TN, primary vaccination with a booster shot is and remains the primary and the safest method for the prevention of severe disease associated with COVID-19.
Some important points:
• 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 or any other drug that should be approved in the future for the treatment of COVID-19. However, if you are worried about any relationship between the cause of your SJS and a new drug you should talk with your physicians and pharmacist.
• It is important to be clear about what drugs were associated with your SJS/TEN in cases you need to be treated for bacterial pneumonia or any other complications which could ensure. It is important for you to know what antibiotics are safe for you to take. If any date please email: firstname.lastname@example.org
Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Eng J Med 2020 Dec 30: NEJMra20335343.