CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
COVID-19 vaccination of the immunocompromised—an n-of-1 observational study
February 2022—The CDC published on Nov. 5, 2021 a report indicating that immunocompromised persons receiving SARS-CoV-2 mRNA vaccines should receive three doses and a booster (MMWR Morb Mortal Wkly Rep. 2021;70[44]:1553–1559). The following n-of-1 observational study suggests that an immunocompromised nonresponder to mRNA vaccine may indeed respond to a second series of SARS-CoV-2 mRNA vaccine.
A 74-year-old male with chronic lymphocytic leukemia in remission since 2007 received two standard doses of Pfizer mRNA vaccine according to established protocol. This patient with hypogammaglobulinemia requires intravenous immune globulin, 35 g, every 10 weeks. Using the semiquantitative SARS-CoV-2 neutralizing antibody test (Advia Centaur, Siemens), no evidence of seroconversion was detected on two occasions, i.e. no antibody was detected 13 days after the second vaccine dose, and again 142 days after the second vaccine dose. These results indicate a nonresponder to the COVID-19 mRNA vaccine.
On Aug. 20, 2021, when booster vaccinations became available, a third dose of Pfizer mRNA vaccine was obtained. Five days later, the antibody to neutralizing spike protein remained negative. This test was repeated on the same Siemens platform 26 days after the booster vaccination and was positive for the first time. This semiquantitative test for antibody to neutralizing spike protein is reported in “units” from 1,000 to greater than 140,000, giving an estimate of the quantity of antibody present. This first positive result was reported as 4,484 units.
These findings suggest a pattern in which a nonresponder to the standard two-dose regimen subsequently developed neutralizing antibody as a primary response to the booster. It was reasoned that a fourth dose of mRNA vaccine would represent the completion of a second attempt of the complete two-dose regimen. This is not unprecedented in that repeating the three-dose vaccination schedule for hepatitis B nonresponders is common.