Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort

Abstract

Background SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI.

Seroconversion after SARS‐CoV‐2 vaccination is protective against severe COVID‐19 disease in heart transplant recipients

“…Furthermore, a fourth vaccine dose resulted in seroconversion in a few more cases. Numerous studies confirmed that a third dose of vaccine increased antibody response against SARS‐CoV‐2 in solid organ transplant recipients 11–13,25–29 . In light of these findings, it became evident that booster vaccine doses would be essential in the prevention strategy against SARS‐CoV‐2.…”

“…Recent publications have reported that older age of the recipient 15,16,29 and certain immunosuppressive regimens 16 predispose transplant recipients to severe SARS-CoV-2 infection. In the current study, seronegative status before infection has been proven to be a significant predictor of severe infection.…”

“…33 An analysis of thoracic and abdominal organ recipients showed a significantly lower rate of positive antibody response after vaccination in those patients who required hospitalization due to SARS-CoV-2 infection compared with nonhospitalized individuals. 29 The ESOT also recommends to use the titer of anti-spike IgG in specific cases to estimate the level of protection of transplant recipients against severe COVID-19. The absence of any detectable antibody response indicates lack of effective protection against severe COVID-19 and may identify patients in need for additional protective strategies.…”

Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS‐CoV‐2 infection

“…Nevertheless, immunocompromized patients with underlying conditions impairing their immune response to vaccines or natural infections are still at increased risk for COVID-19-associated morbidity and mortality. 1,2 States of relative immunologic vulnerability affect the severity of COVID-19, making it crucial to find targeted approaches to manage different levels of clinical complexity. In particular, patients with impaired adaptive humoral immunity have a high risk of prolonged viral shedding, viral rebound, and/or persistent infection.…”

“…From the early months of a deadly infection to the present days, the clinical commitment to the SARS‐CoV‐2 pandemic has significantly decreased due to the effectiveness of global vaccination and antiviral treatments. Nevertheless, immunocompromized patients with underlying conditions impairing their immune response to vaccines or natural infections are still at increased risk for COVID‐19‐associated morbidity and mortality 1,2 . States of relative immunologic vulnerability affect the severity of COVID‐19, making it crucial to find targeted approaches to manage different levels of clinical complexity.…”