key: cord-0875687-e5clbdjr
authors: Squire, Jacqueline; Joshi, Dr. Avni
title: Seroconversion Following COVID-19 Vaccination in Immune Deficient Patients
date: 2021-05-19
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2021.05.015
sha: c729165c2978261844df051bcd959b337d27c17b
doc_id: 875687
cord_uid: e5clbdjr

nan

No conflict of interest for this study for any of the authors.

A Joshi: conception and design, acquisition of data, or analysis and interpretation of data; drafted the article; gave final approval of the version to be published; and agrees to be accountable for all aspects of the work related to its accuracy or integrity. J Squire: made substantial contributions to analysis and interpretation of data; drafted the article; given final approval of the version to be published; and agrees to be accountable for all aspects of the work related to its accuracy or integrity. vaccination. Patients with underlying primary or secondary immunodeficiencies have variable response to vaccination, but inactivated or nonviable vaccines are generally considered safe in immune deficient patients. 1 The efficacy of inactivated vaccines is variable in patients with humoral immune deficiencies, many can mount a protective T-cell dependent antibody response to protein conjugated vaccines, except for patients with congenital agammaglobulinemia such as X-linked agammaglobulinemia (XLA) who may lack the ability to mount any antibody response.

The immune response to SARS-CoV-2 infection itself has demonstrated the interplay between the humoral and cellular adaptative immune systems. Measured response to SARS-CoV-2 infection have demonstrated a prominent CD4+ T-cell response which in turn helps induce antibodies against the spike and nucleocapsid proteins of SARS-CoV-2. 2 Immune response to the mRNA COVID-19 vaccines similarly has been shown to induce a T-cell and neutralizing antibody response. 3 This presence of anti-nucleocapsid and antispike antibodies has been demonstrated to be significantly effective in prevention of subsequent reinfection as well as severe COVID-19 disease. 4, 5 There is currently lack of data on the efficacy of SARS-CoV-2 vaccination in immune deficient patients. We report our early experience from eleven immune deficient patients from our institution assessing vaccine responses to mRNA SARS-CoV-2 vaccines.

Retrospective chart review was performed as part of an institutional review board approved study. Eleven patients with underlying immune deficiency received an mRNA COVID-19 vaccine, from either Pfizer-BioNTech or Moderna (Table 1 ) and tolerated it well.

Patients were between the age of 25 to 75 years, 6/11 (54.5%) were male. Most patients (6/11) had common variable immunodeficiency (CVID), one XLA, one Wiskott-Aldrich Syndrome (WAS), one DiGeorge Syndrome, and two patients had hypogammaglobulinemia (isolated low IgG levels). Majority (8/11) were on supplemental immunoglobulin therapy with intravenous immunoglobulin (IVIG) every 3-4 weeks, one received subcutaneous immunoglobulin (SCIG), and three patients were not on any immunoglobulin replacement. Only two patients (patient #4 and #11) were receiving additional immunomodulators for associated conditions. Patient #4 was receiving hydroxychloroquine 200 mg daily for urticarial vasculitis and budesonide 9 mg for enteropathy. CoV-2 antibodies that should be obtained to be considered "protected" is unknown, it has been projected that immunoglobulin lots could contain similar concentrations of SARS-CoV-2 neutralizing antibodies as the convalescent plasma used in COVID-19 treatment by July 2021. 7 Despite this possibility, the risk of severe COVID-19 illness and related complications indicates that measures that improves and hasten protection from COVID-19 are needed. Our early report of eleven cases presented here demonstrate that vaccination with an mRNA COVID-19 vaccine is safe and can result in high level antibody titers in immune deficient patients (with the exception of XLA), similar to those reported in health-care workers following vaccination. 8 Of note, patient #11, who was on moderate immune suppression with mycophenolate and belimumab, had the lowest recorded titer at 7.8 U/mL, though still above the threshold of seroconversion (>0.8U/ml). Transplant patients receiving anti-metabolite maintenance therapy have also been shown to be less likely to develop antibody response to the first COVID-19 vaccine. 9 Patient #11 may demonstrate that patients on maintenance immune suppression mount less robust responses to vaccination. Aside from developing high titer antibodies, cellular response to vaccination is an important aspect of vaccine effectiveness. It has been demonstrated that patients with XLA can mount normal dendritic and T-cell responses to influenza vaccination. 10 Therefore, COVID-19 vaccination should be encouraged even in those unlikely to mount significant antibody response.

With natural COVID-19 infection, majority of patients will develop both anti-spike and anti-nucleocapsid antibodies, but following COVID-19 vaccination only anti-spike antibodies will be produced. 8 The measurement of both antibodies simultaneously can help distinguish between response to natural infection (positive to both antibodies) versus response to vaccination (positive anti-spike antibody and negative anti-nucleocapsid antibody). By measuring both the SARS-CoV-2 spike antibody and the nucleocapsid antibody in the majority of the patients reported here, this illustrates response to the vaccine rather than antibodies from immunoglobulin replacement which would be expected to contain both anti-spike and anti-nucleocapsid antibodies at this time due to 

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