Immunologic Monitoring of a Breakthrough Infection in a Heart and Kidney Transplant Recipient

Abstract

IntroductionSolid organ transplant recipients (SOTR) have lower SARS-CoV-2 spike seroconversion than healthy subjects (HS) following vaccination. A breakthrough (BT) infection is defined as the detection of SARS-CoV-2 in a respiratory specimen after a person is ≥14 days after completing the recommended doses for a vaccine. We report a case of SARS-CoV-2 BT infection in a SOTR who was immunologically followed longitudinally following vaccination.Case ReportA 44-year-old man with a history of non-ischemic cardiomyopathy (NICM) and end stage renal disease had undergone heart and kidney transplantation in December 2017 with thymoglobulin induction. His NICM was secondary to radiation for non-Hodgkin's lymphoma treated with autologous bone marrow transplant in 2001. Maintenance immunosuppression consisted of sirolimus 2mg daily, tacrolimus 2mg twice daily (BID), and prednisone 5mg daily at his 1st Moderna vaccine in April 2021. In anticipation of surgery, sirolimus was stopped and mycophenolate mofetil (MMF) 500mg BID was started. He was on this regimen at the time of his 2nd Moderna vaccine. Sirolimus was restarted in July and increased to 1mg daily while continuing MMF 500mg BID, tacrolimus, and prednisone. At the end of July, the patient was exposed to several family members with COVID-19. He tested positive 89 days after his 2nd Moderna vaccine (cycle threshold of 33.5). He was asymptomatic at the time, but later developed fever, myalgias, headache, and loss of taste and smell and was treated with casirivimab and imdevimab monoclonal antibody (mAb) infusion. We assessed the patient's immunologic response 14 days post 2nd Moderna vaccination and at BT infection prior to mAb infusion and compared this to HS. The patient developed SARS-CoV-2 spike-specific CD4+ T cells at 14 days post 2nd mRNA vaccine at a frequency below the average frequency for HS. At BT infection, the patient did not have SARS-CoV-2 spike-specific CD4+ T cells, partly due to virus induced lymphopenia. The patient did not develop spike-specific CD8+ T cells, spike IgG or neutralizing antibodies at 14 days post 2nd Moderna vaccination or at BT infection.SummaryThe patient developed SARS-CoV-2-specific CD4+ T cells following vaccination. His uneventful recovery may be secondary to these SARS-CoV-2 specific CD4+ T cells post vaccination as well as receiving mAb therapy 8 days post infection.