Recently, researchers posted the results of a retrospective observational cohort study to the medRxiv* preprint server in which they determined the humoral and cellular responses in immunosuppressed patients (ISP) to primary and booster doses of coronavirus disease 2019 (COVID-19) vaccines.
Study: Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients. Image Credit: Carl DMaster/Shutterstock
As per estimates, at least one in every 25 individuals in the United States is immunocompromised and is at risk for severe COVID-19 and vaccine-breakthrough infections. Studies have shown that in immunocompromised individuals, humoral response following COVID-19 vaccination is poor, and T cell response is less impaired but not well characterized. The steady decline in antibody titers over time led to booster campaigns in many nations. Booster doses are of significant importance in the ISPs as several reports have indicated poor response to primary doses of vaccination.
The study
In the present study, researchers compared the humoral and cellular responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ISPs after the administration of primary and booster shots of COVID-19 vaccines. Between January 1, 2021, and November 15, 2021, about 496 fully vaccinated individuals were included as participants who received clinical testing for anti-SARS-CoV S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon-γ release assay (IGRA).
The participants included in the study had no known history of COVID-19 infection. For the study, patients underwent clinical testing for anti-S1 IgG or IGRA at least 14 days following the second dose of mRNA-1273 or BNT162b2 vaccines or a single dose of Ad26.COV2.S.
Booster analysis included those patients with anti-S1 IgG or IGRA results collected at least seven days following the administration of any of the three vaccines as a booster shot. Eighteen volunteer health care workers (HCWs) who were immunocompetent were included as a reference cohort.
ISPs were defined as those receiving active immune-suppressive/modulatory therapy (ISMT), including chemical drugs, biologics, and cellular therapy like CAR-T or HSCT (hematopoietic stem cell transplant) at the time of or four weeks before primary vaccination or anytime between vaccination and IGRA or anti-S1 IgG testing.
Patients were categorized as ISPs with immunosuppressive conditions like active heme malignancy (hematologic malignancy with active disease at the time of vaccination), inactive heme malignancy (complete response to therapy), primary anemia, solid malignancy (solid non-hematologic malignancy with prior or active chemo-/radiotherapy), solid organ transplant, autoimmune disorders, and immunodeficiency. Patients without active ISMT or a history of immunosuppressive diseases were classified into a non-ISP (NISP) cohort.
Findings
The authors found a significant statistical difference in the positivity rates of anti-S1 IgG and IGRA in the ISPs. Both anti-S1 and IGRA results were available for about 381 ISPs; 51% were positive for both, 18% were negative for both, and 20% were IGRA-only positive, and 11% were anti-S1 IgG-only positive. The anti-S1 IgG and IGRA positivity rates were lower for ISPs with a single disease category than those on ISMT. ISPs not on ISMT with primary anemia or solid malignancy reported higher rates of humoral and cellular response. Patients with inactive heme malignancy and autoimmune disorders had high rates of cellular response and lower rates of humoral response.
Patients with active and inactive heme malignancy not on any ISMTs showed that those with B cell lymphoma were 61% IgG positive, and those with acute leukemia were 100% IgG positive. Likewise, cellular responses were higher in these patients, with 100% and 80% of acute leukemia patients and B cell lymphoma patients, respectively, being IGRA positive.
Quantitative analysis of vaccine response over time after primary vaccination on an average revealed a steady decline of both humoral and cellular responses in ISP, NISP, and HCW cohorts. Following a booster shot, the changes observed in humoral and cellular responses were not statistically significant in ISPs. An anamnestic booster response was observed in several ISPs; 10 patients showed an anamnestic humoral response, and two patients had T cell anamnestic booster response. Importantly, 35 ISPs with a low humoral response after the first vaccine dose demonstrated marked anamnestic booster response.
Conclusions
Based on the study findings, no conclusive evidence of a decline in either humoral or cellular response over time was found between the ISP, NISP, or HCW cohorts. The study found that boosters do not significantly improve T cell responses in ISPs. Notably, the ISPs who were on ISMTs and had lower humoral responses following primary vaccination showed an anamnestic booster response.
In contrast, the ISPs with underlying immunosuppressive diseases were unlikely to reproduce the anamnestic response. This finding suggests that booster doses can help overcome the immunosuppressive effects of ISMTs. Taken together, the findings of the present study provide a basis to optimize vaccination strategies in immunosuppressed patients.
*Important information
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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