Is Covid-19 vaccine effective in immunocompromised patients?

The short answer is that we don’t have any solid data on the performance of Covid-19 among immunocompromised (IC) patients at this time because the large trials used to clear the available vaccines for FDA Emergency Use Authorization essentially excluded IC subjects (1,2). 

However, despite a potentially blunted response, the immunogenicity of the Covid-19 vaccine may be sufficient to reduce the risk of serious disease. The CDC and the American Society of Clinical Oncologists support Covid-19 vaccination of IC patients as long as there are no contraindications and patients are counseled about the uncertainty in vaccine efficacy and safety in this particular population (3,4).

 For patients undergoing treatment for cancer, the ASCO believes that Covid-19 vaccine may be offered in the absence of any contraindications.  To reduce the risk of Covid-19 while retaining vaccine efficacy, it recommends that the vaccine be given between cycles of therapy and after “appropriate waiting periods” for those receiving stem cell transplants and immunoglobulin therapy (4).

Previous experience with pneumococcal and influenza vaccine in IC patients have reported frequent suboptimal immunological response (2). Concomitant treatment with infliximab or other immunomodulatory drugs have had a negative impact on seroconversion after influenza vaccination. Similarly, in patients with Crohn’s on immunosuppressives, immune response to polysaccharide pneumococcal vaccine has been blunted (2). 

Nevertheless, the benefits of vaccination may still outweigh any risks of adverse events in this population. In fact, the CDC routine vaccination schedule for adults includes immunocompromised patients (5).  

At this time, given the seriousness of the Covid-19 pandemic and higher risk of severe disease among many IC patients, offering Covid-19 vaccine to these patients (with aforementioned caveats) seems prudent. 

 

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References

  1. Kumar A, Quraishi MN, Segal JP, et al. Covid-19 vaccinations in patients with inflammatory bowel disease. Lancet 2020;4:965-6. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30295-8/fulltext
  2. Polack FP, Thomas SJ, Ktichin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-15. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
  3. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html. Accessed Feb 14, 2021.
  4. American Society of Clinical Oncologists. Covid-19 vaccine and patients with cancer.. https://www.asco.org/asco-coronavirus-resources/covid-19-patient-care-information/covid-19-vaccine-patients-cancer Accessed Feb 14, 2021
  5. CDC. Immunization schedules. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html Accessed Feb 14, 2021.  

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is Covid-19 vaccine effective in immunocompromised patients?

My patient with rheumatoid arthritis might have been exposed to tuberculosis. Does immunosuppressive therapy affect the results of interferon gamma release assay (IGRA) testing for latent tuberculosis?

The weight of the evidence to date suggests that immunosuppressive therapy, including steroids, other oral immunosuppressants and anti-tumor-necrosis factor (TNF) agents, may negatively impact IGRA results.1

In some ways the finding of false-negative IGRA in the setting of immunosuppression is intuitive since many immunosuppressive agents are potent inhibitors of T cells and interferon-gamma response. 1,2 Despite this, the initial reports have been somewhat conflicting which makes a 2016 meta-analysis of the effect of immunosuppressive therapy on IGRA results in patient with autoimmune diseases (eg, rheumatoid arthritis, lupus, inflammatory bowel disease) particularly timely. 1

This meta-analysis found a significantly lower positive IGRA results among patients on immunosuppressive therapy ( O.R. 0.66, 95% C.I. 0.53-0.83). Breakdown by IGRA test showed a significant association between QuantiFERON-TB Gold In-Tube and lower positive results and a trend toward the same with T-SPOT though the latter did not reach statistical significance with fewer evaluable studies (O.R. 0.81, 95% C.I 0.6-1.1).   Breakdown by type of immunosuppressant showed significantly negative impact of corticossteroids, other oral immunosuppressants, and anti-TNF agents for all. Some studies have reported daily steroid doses as low as 7.5 mg-10 mg may adversely impact T-cell responsiveness in IGRA. 3,4

So, whenever possible, testing for latent TB should be performed before immunosuppressants are initiated.

Bonus Pearl: Did you know that an estimated one-third of the world’s population may have latent TB?

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References

  1. Wong SH, Gao Q, Tsoi KKF, et al. Effect of immunosuppressive therapy on interferon gamma release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis. Thorax 2016;71:64-72. https://thorax.bmj.com/content/thoraxjnl/71/1/64.full.pdf
  2. Sester U, Wilkens H, van Bentum K, et al. Impaired detection of Mycobacterium tuberculosis immunity in patents using high levels of immunosuppressive drugs. Eur Respir J 2009;34:702-10. https://erj.ersjournals.com/content/34/3/702
  3. Kleinert S, Kurzai O, Elias J, et al. Comparison of two interferon-gamma release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases. Ann Rheum Dis 2010;69:782-4. https://ard.bmj.com/content/69/4/782
  4. Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S, et al. Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population. J Rheumatol 2008;35:776-81. https://www.ncbi.nlm.nih.gov/pubmed/18398944
My patient with rheumatoid arthritis might have been exposed to tuberculosis. Does immunosuppressive therapy affect the results of interferon gamma release assay (IGRA) testing for latent tuberculosis?

When should I suspect spontaneous coronary artery dissection in my patient with chest pain?

Spontaneous coronary artery dissection (SCAD) is defined as the separation of the walls of the coronary artery.1 It is thought that hemorrhage into the false lumen can result in compression of the true lumen, leading to ischemia. Although its exact incidence is unknown, SCAD has been estimated to account for up to 35% of myocardial infarctions in women younger than 50 y of age.2-3

SCAD is often associated with acute chest pain with presentations ranging from acute coronary syndrome (ACS) to sudden cardiac death.1,4 Diagnosis is typically accomplished with coronary angiography and, increasingly, newer modalities such as optical coherence tomography, intravascular ultrasound, and cardiac CT angiography.1

Clinical features that should raise suspicion of SCAD are shown (Table)5. Among many risk factors, myocardial infarction in younger women and the absence of traditional cardiovascular risk factors or lack of typical atherosclerotic lesions in coronary arteries should be potential flags for the possibility of SCAD.

Although the optimal management of SCAD is unclear, conservative therapy with aspirin, clopidogel and beta-blockers has often been recommended5 .  Percutaneous coronary intervention (PCI) carries a risk of worsening the dissection or causing additional dissections in such patients1. Revascularization is often reserved for those with hemodynamic instability, persistent ischemia, sustained ventricular tachycardia or fibrillation, or left main dissection.1,5

Table. Clinical features that raise suspicion of SCAD5 ______________________________________________________________________________________________________________
Myocardial infarction in young women (especially age ≤ 50 y)
Absence of traditional cardiovascular risk factors
Little or no evidence of typical atherosclerotic lesions in coronary arteries
Peripartum state
History of fibromuscular dysplasia
History of relevant connective tissue disorder (eg, Marfan’s syndrome, Ehler Danlos syndrome)
History of relevant systemic inflammation (incl. SLE, IBD, sarcoidosis, polyarteritis nodosa)
Precipitating stress events caused by emotional or intense physical factors ______________________________________________________________________________________________________________
SLE: Systemic lupus erythematosus; IBD: Inflammatory bowel disease (eg, Crohn’s, ulcerative colitis).

References

  1. Saw J, Mancini GB, Humphries KH. Contemporary Review on Spontaneous Coronary Artery Dissection. J Am Coll Cardiol 2016;68:297-312.
  2. Rashid HN, Wong DT, Wijesekera H, et al. Incidence and characterisation of spontaneous coronary artery dissection as a cause of acute coronary syndrome – a single-centre Australian experience. Int J Cardiol 2016;202:336-8.
  3. Nakashima T, Noguchi T, Haruta S, et al. Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: a report from the Angina Pectoris-Myocardial Infarction Multicenter Investigators in Japan. Int J Cardiol 2016;207:341-8.
  4. Lettieri C, Zavalloni D, Rossini R, et al. Management and long-term prognosis of spontaneous coronary artery dissection. Am J Cardiol 2015;116:66-73.
  5. Yip A, Saw J. Spontaneous coronary artery dissection-A review. Cardiovasc Diagn Ther 2015;5:37-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329168/pdf/cdt-05-01-037.pdf

Contributed by Mahesh Vidula, MD, Mass General Hospital, Boston, MA.

When should I suspect spontaneous coronary artery dissection in my patient with chest pain?