The main finding in our study was that among these long-term allogeneic HSCT survivors, humoral B cells and ex vivo Both T-cell responses were strong. . This robustness may be due to the fact that most patients had previously been infected with COVID-19, and 62% had previously confirmed SARS-CoV-2 infection. An even larger proportion probably had subclinical infections, and nucleocapsid antibodies may have been below the detection threshold before sampling. Additionally, a booster dose of Comirnaty Omicron XBB.1.5 further enhanced the virus-specific immune response, whereas the response was significantly reduced before and after the booster in patients receiving immunosuppressive therapy.
There was no correlation between previously confirmed SARS-CoV-2 infection and antibody levels or T cell responses. This may be explained by the much higher frequency of previous COVID-19 cases and the acquisition of hybrid immunity from infection and vaccines. It enhances the immune response even among immunocompromised individuals12,13. During the first wave of the pandemic, SARS-CoV-2 PCR was generally available through self-testing, and testing was widespread in both inpatient and outpatient settings, but since late 2022, SARS-CoV-2 2 Testing is primarily limited to individuals. At risk of serious illness or early intervention, or already hospitalized. 35% of participants in this study had antibodies against nucleocapsids (nIgG), which is consistent with a report from the Swedish Public Health Agency that suggests an outbreak period in 202314. However, the clinical significance is significantly weakened compared to the early stages of infection. A pandemic has occurred among allogeneic HSCT recipients15.
Although we observed an increase in IL-2 after booster vaccination, there was no significant change in IFN-γ production after booster vaccination. This finding is consistent with other studies investigating cytokine profiles after COVID-19 mRNA vaccination, showing that IL-2 is significantly increased by SARS-CoV-2-specific CD4+ cells after immunization. 16 is the major cytokine induced.
Significant gender differences were also observed in prebooster humoral immune responses in long-term allogeneic HSCT survivors, with female participants having higher antibody levels than male participants despite no difference in the number of previous doses. Showed. Last dose or presence of cGvHD. This observation is consistent with a growing body of research suggesting that gender may influence the immune response to vaccination17.
The Swedish Public Health Agency recommends booster doses of the coronavirus disease (COVID-19) mRNA vaccine once or twice a year for immunocompromised patients, but this population is heterogeneous. , allowing the attending physician to advise on booster vaccination strategies. Some facilities choose to check serum antibody levels after the initial vaccination schedule to determine the need for subsequent repeat vaccinations. Tailored vaccination regimens, while promising, pose challenges because there are no clearly defined thresholds that correlate with protection against severe COVID-19. Additionally, implementation of an immune-inducing vaccination strategy requires agreement on a sampling schedule. Additionally, considerations regarding the inclusion of comorbidities, planned immunosuppressive treatments, or the emergence of novel SARS-CoV-2 variants complicate the decision-making process in this regard. To this end, the study’s finding that pre-booster immune responses were high in most patients is encouraging, even though a significant amount of time has passed since the last vaccination. The exception was long-term allogeneic HSCT survivors who continued immunosuppressive treatment, in whom COVID-19-specific immune responses were diminished.
Strengths of the current study include parallel monitoring of aspects of virus-specific B- and T-cell-mediated immunity and sampling of participants immediately before and 4 weeks after the booster immunization. The sample size of the study was relatively small, and perhaps important for outcomes, the median time since transplantation was 9 years. By taking these precautions, we believe that our findings can also be applied to long-term allogeneic HSCT survivors. Although there was no obvious effect of GvHD, patients receiving immunosuppressive treatment in this study, primarily a combination of low-dose prednisone and ruxolitinib, had a significantly reduced immune response.
One patient underwent Ig exchange and had previously confirmed COVID-19 infection by both PCR and nIgG. He had high antibody levels at both pre-booster and post-booster samplings, with a 5-fold increase in sIgG and a 3-fold increase in IL-2 post-booster compared to pre-booster. This suggests that his Ig exchange did not substantially confound the results.
In conclusion, booster immunization strategies in immunocompromised patients remain difficult given the heterogeneity of this population. Of these long-term allogeneic HSCT survivors, most had previously been infected with COVID-19, and the majority had strong immune responses before and after the booster. However, an exception was observed in allogeneic HSCT recipients receiving immunosuppressive therapy, where COVID-19-specific immune responses were reduced before and after boosting.
