Just wanted to let everyone know that the following brief article by Dr. Kirk Druey and colleagues at the U.S. National Institutes of Health has just been published in the prestigious Annals of Internal Medicine. (The full piece, including two accompanying tables and five footnotes, can be seen by following the link provided at the bottom.)
The conclusion is that, based on experience with three individuals -- one of whom died -- it is recommended that patients with a diagnosis, or a suspected diagnosis, of SCLS should receive IVIG before they get the Covid-19 vaccine.
Severe Exacerbations of Systemic Capillary Leak Syndrome After COVID-19 Vaccination: A Case Series
By Meghan Matheny, Noble Maleque, Natalie Channell, A. Robin Eisch, Sara C. Auld, Aleena Banerji, and Kirk M. Druey, National Institutes of Health, 15 June 2021, Annals of Internal Medicine
Background: Flares of systemic capillary leak syndrome (SCLS) release plasma into peripheral tissues, which typically leads to hypotensive shock and multiple organ dysfunction (1). Anasarca and compartment syndromes may develop as a result of excessive intravenous (IV) fluid administration (2). Between episodes, patients are typically asymptomatic. The diagnosis of SCLS is based on characteristic clinical findings that include hypotension, hemoconcentration, and hypoalbuminemia. Prophylaxis with IV immunoglobulin (IVIG) is disease sparing and improves survival (3).
We describe 3 patients who had severe flares of SCLS immediately after receiving standard doses of the COVID-19 vaccines that have emergency use authorization from the U.S. Food and Drug Administration. These events were classified as non–dose-related, unexpected, and serious adverse events according to the World Health Organization.
Objective: To alert clinicians to the possibility of SCLS-like events immediately after COVID-19 vaccination.
Case Reports: Patient demographic characteristics and hospital experiences are detailed in Table 1, and the results of selected laboratory tests are summarized in Table 2.
Patient 1 was diagnosed with SCLS with monoclonal gammopathy of unknown significance in 2006 after 2 characteristic episodes. She declined IVIG treatment but had no disease relapses during 15 years of treatment with oral theophylline and terbutaline. In March 2021, she presented to the emergency department of Exeter Hospital 2 days after receiving a single dose of the Ad26.COV2.S vaccine (Janssen). She had hypotension and tachycardia and developed protracted shock and anasarca. Results of blood cultures and nasal swab polymerase chain reaction tests for SARS-CoV-2 were negative. After she developed additional SCLS-related complications and continued to deteriorate, care was discontinued on hospital day 7.
Patient 2 had a normal vaginal delivery in 2002 followed by hypotension and edema, which was attributed to amniotic fluid embolism. In 2018, she had another episode of hypotension (systolic blood pressure was approximately 50 mm Hg) and anasarca after several days of upper respiratory symptoms. This episode was attributed to sepsis, although blood culture results were negative. In February 2021, she presented to the emergency department of Virginia Hospital Center 2 days after receiving the second dose of the mRNA-1273 vaccine (Moderna). She had hypotension and tachycardia and later developed shock and anasarca. Results from a nasal swab polymerase chain reaction test for SARS-CoV-2 and a screen for other common respiratory pathogens (Table 1) were negative. All symptoms resolved with supportive treatment. Treatment with IVIG was started; monoclonal gammopathy of unknown significance (IgG κ) was detected during an asymptomatic period.
Patient 3 had syncope and seizures in December 2020 and again in February 2021. His neurologic work-up, which included an electroencephalogram and magnetic resonance imaging of the brain, was normal. In April 2021, he presented to the local emergency department 1 day after receiving the second dose of the BNT162b2 vaccine (Pfizer-BioNTech). He had tachycardia and developed status epilepticus and was transferred to Maine Medical Center. During transport, he developed a cardiac arrest with pulseless electrical activity, which responded to cardiopulmonary resuscitation and epinephrine. Blood and urine cultures were negative, as were results from multiple nasal swab polymerase chain reaction tests for SARS-CoV-2. Monoclonal gammopathy of unknown significance was not detected by serum or urine immunofixation during the hospitalization.
Discussion: We describe 3 patients with SCLS or a history suggestive of SCLS who developed life-threatening flares 1 to 2 days after COVID-19 vaccination. We believe these patients identify SCLS as a risk factor for the development of serious adverse reactions after COVID-19 vaccination. However, we recognize that these observations do not rule out other causes of these flares. For example, infection-related symptoms precede 44% to 64% of all acute flares (1, 4), and flares have been reported with SARS-CoV-2 infection (5). However, we were unable to identify any of these other triggers.
Systemic capillary leak syndrome is a rare disease, and persons without a diagnosis of SCLS or a history suggestive of SCLS are unlikely to develop a flare after COVID-19 vaccination. However, some persons with unexplained episodes of hypotension and edema may have undiagnosed SCLS. In addition, we note that none of the 3 patients we describe were receiving IVIG prophylaxis when they were vaccinated and that we have received no reports of SCLS flares after COVID-19 (or other antiviral) vaccinations among our 78 patients with SCLS, most of whom are receiving IVIG prophylaxis. Therefore, we recommend that patients with a diagnosis or a suspected diagnosis of SCLS should receive IVIG prophylaxis before vaccination.
This is so strange -- I'm Patient 2! The first time I came to Rare Share the first post I saw was "A Warning for Those Not on IVIG" and I thought, wow, that's about me. I'm very grateful for this community and for Dr. Druey. (Should I tell him I was discharged on Day 11, not 7? ;) )
I will admit I'm already feeling frustrated with the IVIG treatments. I don't know how people with jobs are supposed to take 3-4 days off every month for infusions and recovery from the infusions. Does anyone get less than the 2g/2kg dose? A smaller dose would at least cut that time in half. Thanks!
Jenh,
To your first question, yes, do tell Dr. Druey right away because there may still be time for a minor correction, since the piece has been accepted but is still in the pre-publication stage.
To your second question, not everybody is knocked out or adversely affected by the infusions. I've been getting them every 4 weeks for over eleven years while holding a full-time job, and I've never had to take a single day off. For example, the infusion cycle only takes me two consecutive mornings, and I probably receive more medication than you do -- namely, I get 90 gr/day or almost a liter (0.9 liters/day, to be exact). In those days I work late to make up for the morning hours I missed.
The key is the speed of the infusions, and your body's reaction to that speed. It's been many years now that I start slow (0.11 liters/hour) for 15 minutes, then I double that (to a speed of 0.22 liters/hour) for another 15 minutes, and if I have no adverse reaction, which has been the case 99% of the time, then I double the speed again (to 0.44 liters/hour), which is close to the maximum speed recommended by the manufacturers for people in my weight category. Therefore, I'm in and out in 3-4 hours, including an hour or so of waiting time, registration and prep (with Tylenol and Benadryl), depending also on how busy and good the infusion nurses are -- because three speeds and five bottles are involved each day. Needless to say, these infusion speed instructions were agreed upon with, and are spelled out in writing by, my prescribing physician.
I encourage you to discuss infusion speeds with your physician with the view to speeding up the process and seeing how your body tolerates it. I would have headaches a day or two after each infusion cycle every time that I speeded up the process, but the headaches would go away with Tylenol and never return as my body got used to the increasingly faster infusion speeds. But granted, not everybody reacts the same way to IVIG and to faster infusion speeds; not everyone is willing to experiment with themselves; and not all jobs and managers are equally flexible.
A minority of SCLS patients have tired of the infusions, or they never sought or obtained insurance coverage for them. They decided to play -- or were forced to play -- the equivalent of Russian roulette. Many of them eventually had a monster episode, and/or were mismanaged at the hospital, and so they died.
The article details the experience of three individuals who experienced a classic episode of SCLS, one of whom died as a result. That could have been you. Think about that every time you go for your infusion and get frustrated.
Hi Aporzeca,
I'm happy to learn that you and everybody here are staying safe and sound so far.
This is to clarify that, once my son has been off from IVIG for over 2 years, so Covid vaccine should also not be injected (if available) to avoid a trigger, right? If want to get it, he should get Ivig first, right?
Though to my understanding, whatover is also risky.
Thank you very much and wish good luck to everybody!
Nhan,
Yes, you understood correctly, your son should get a dose of IVIG a few days before getting a Covid vaccine, and you can refer your doctor to this article.
How were you diagnosed with SCLS? What kind of doctor diagnoses this? My daughter has passed away, as I mentioned earlier, but I am trying to get her a post-mortem diagnosis so her death certificate will accurately reflect the cause of death (they listed it as ultimately being caused by another syndrome she had, Long QT, and in a round-about way it was due to the need for the surgery, but the mechanical aspects were NOT from Long QT). Are there any doctors that you are aware of that will look at medical records and make post-mortem diagnoses? Thank you!
ShaunaHatch,
So terribly sorry to hear about your daughter's passing!
Your best bet is for the physician most acquainted with your daughter, and thus in possession of, or able and willing to share her medical and hospital records with your permission, to request such a consultation from Dr. Kirk Druey at NIH, see contact infomation at https://ned.nih.gov/search/ViewDetails.aspx?NIHID=0010170114
Thank you!